NACO | Blended Clinical Training LMS - Table of Contents National... · 2020. 10. 27. · (Current NACO treatment guidelines for First-line ART recommend three drug combination therapy

National Guidelines on Second-line and Alternative First-line ART For Adults and Adolescents May 2013 1

Table of Contents

ChapterAcronyms and Abbreviations ............................................................................................. 3

Introduction and Preamble ................................................................................................ 5

Section I: Technical Guidelines ........................................................................................... 7

First Line & Second Line ART Regimen ................................................................ 7

Substitutionvs.Switch ......................................................................................... 7

AlternativeARV Drugs For Intolerance to ZDV/TDF and NVP/EFV: Substitution .................................................................................. 9

MonitoringPatientsonFirstLineART for Failure ................................................ 12

IdentifyingTreatmentFailure .............................................................................. 13

Protocol for determining ART failure (Protocol A1.1) at ART centers ............................................................................. 16

Management Protocol based on SACEP decision and Viral load test Results .......................................................................................... 19

InitiatingthestandardizedNACOSecond-LineRegimen ........................................... 21

DrugInteraction: ................................................................................................. 23

Second-LineARTandTBTreatment .................................................................... 25

LaboratorymonitoringofpatientsonSecondLineRegimen .............................. 27

AdherenceandSecond-LineART ......................................................................... 27

Section II: Operational Guidelines ...................................................................................... 31

StateAIDSClinicalExpertPanel(SACEP) ............................................................. 31

EligibilityandcriteriaforprovisionofSecondLineART ...................................... 34

ProtocolforSACEPreview ................................................................................... 34

TORofadditionalmanpower:SACEPcoordinator ............................................... 36

Section III: M & E Tools ....................................................................................................... 39

InstructionsforMonitoring/recordsKeepingforSecondLineART ..................... 39

Section IV: Laboratory Guidelines ...................................................................................... 45

Introduction: ........................................................................................................ 45

IntendedUseofHIV-1PVLAssayinACO’s SecondLineARTInitiative: .................................................................................. 45

TechniquesofHIV–1PVLAssay: ........................................................................ 48

PlasmaViralLoadAssayscurrentlyinuse inNACO’sSecond-LineRollOut: .......................................................................... 49

SpecimenCollection,Storage,andTransportation .............................................. 51

FactorstobeconsideredwhileInterpretingtheViralLoadResults: ................... 55

LimitationofViralLoadAssays: ........................................................................... 56

2 National Guidelines on Second-line and Alternative First-line ART For Adults and Adolescents May 2013

StandardizationofHIV-1PlasmaViralLoadReporting .............................................. 56

QualityAssuranceforHIV-1PlasmaViralLoadTesting: ............................................ 57

OperationalPlanforHIV-1ViralLoadTestingandEQAS ..................................... 59

PrecautionsandSpecificInstructionsforReagentsandEquipments .................. 61

Troubleshooting ................................................................................................... 63

DBScollectionforallpatientsundergoingViralLoadTesting ...................................63

Annexure

Annex I ........................................................................................................................ 67

Annex II ................................................................................................................ 71

Annex III ............................................................................................................... 73

Annex IV .............................................................................................................. 74

Annex V ............................................................................................................... 78

Annex VI .............................................................................................................. 79

AnnexVII(a)–ViralLoadTestRequisitionForm ................................................ 81

AnnexVII(b)–COBASAmplicorReportingFormat .............................................. 82

AnnexVII(c)–TaqmanReportingFormat ........................................................... 83

AnnexVII(d)–ViralLoadResultForm,AmplicorHIVMonitoring,v1.5 .............. 84

Annex VIII ............................................................................................................ 85

AnnexIX–SecondLineReporting ....................................................................... 88

1SL+AL:SACEPRegisterforAlternativeFirstLine& SecondLineART(AdultsandChildren) ...................................................... 88

2AL:AlternativeFirstLineFormatforSACEP Meeting(Adult&Children) ........................................................................ 90

2 SL: Second Line Format for SACEPMeeting(Adult&Children) ............................................................ 92

3AL+SLCombinedMonthlyReporting FormatforSecond&AlternativeFirstLineART ......................................... 94

4AL:ListofpatientsonAlternativeFirstLineART ..................................... 100

4SL:ListofPatientsonSecondLineART ................................................... 101

5SL:CentreWise(LinkedCentreInformation) breakupforPLHIVInitiatedonSecondLineART ................................... 102

Annexure X .......................................................................................................... 103

Acknowledgements ............................................................................................................. 105

3National Guidelines on Second-line and Alternative First-line ART For Adults and Adolescents May 2013

Acronyms and Abbreviations

3TC LamivudineABC AbacavirAIDS AcquiredImmunodeficiencySyndromeART AntiretroviralTherapyARV AntiretroviralATV AtazanavirAZT/ZDV ZidovudinebPI BoostedPICD4count CD4+T-LymphocyteCOE CentersofExcellenced4T StavudineddI DidanosineEC Enteric CoatedEFV EfavirenzFDC Fixed-DoseCombinationFTC EmtricitabineHb HemoglobinHIV HumanImmunodeficiencyVirusIDV IndinavirLPV LopinavirNACEP NationalAIDSClinicalExpertPanelNFV NelfinavirNNRTI Non-NucleosideReverseTranscriptaseInhibitorNRTI NucleosideReverseTranscriptaseInhibitorNVP NevirapinePI ProteaseInhibitorPLHIV PeopleLivingwithHIV/r Low-DoseRitonavirRTV RitonavirSACEP StateAIDSClinicalExpertPanelSQV SaquinavirTDF TenofovirDisoproxilFumarateVL Viral Load



Introduction and Preamble

TheNationalARTprogrammelaunchedon1stApril2004ineightgovernmenthospitalsinsixhighprevalencestateshassincebeenscaledupto400ARTcentreswhereina total of around 16,00,000 patients have been registered inHIV care and nearly6,00,000patientsarecurrentlyonART.ThenationalprogrammeprovidesfreeFirstline,alternateFirstlineandSecondlineantiretroviraldrugstoadultsandchildrenaspertheireligibility.

ATechnicalResourceGroup(TRG)onARThasbeenconstitutedatNACOthatmeetsregularlytoupdateandformulatethetechnicalguidelinesforFirstlineandSecondlineART.AllARTcentersinthecountryhaveaccesstoSecondlineARTbutforinitiationofSecondlineARTaround41centershavebeenidentified.Theseinclude10CentresofExcellence,7PediatricCentresofExcellenceand20ARTPluscenters.ThisistoensurethatonlythosewhohaveconfirmedfailuretoFirstlineARTareinitiatedonSecondline treatment thereby minimizing unnecessary switches. Besides this, a specialtrainingofhealthcareprovidersatallARTcenters isdoneonmonitoringpatientsinitiatedonantiretroviraltherapyalongwithregulatorymechanismstominimizethechancesofresistanceduetoirrationalprescriptions.Inordertoensurehighqualityofcare,toensurethatonlyeligiblepatientsarestartedonSecondlineARTandmaintainuniformityintreatment,StateClinicalExpertPanels(SACEP)havebeenconstitutedatallCoEsandARTpluscenterswhereSecondlineARTisinitiated.EverypatientthatisreferredtothesecenterswithasuspectedfailuretoFirstlineARTisFirstreviewedbySACEPand,ifthesuspectedtreatmentfailureisconfirmedbyViralloadtesting,theneligiblepatientsareinitiatedonSecondlineARTafteradequatepreparedness.AfterthepatientsbecomestableonSecond lineART, theyare transferredback to theirreferringARTcentre.TheycontinuetogettheirSecondlinedrugsattheirownARTcenterthereafter.AlsocomplicatedcasesthatneedfurtherreviewandopinionarereferredtoNationalAIDSClinicalExpertPanel(NACEP)atNACO.

The initial roll out of Second line ART was done at 2 Centers of Excellence:GovernmentHospitalofThoracicMedicine(GHTM),TambaramandSirJJHospital,Mumbai.During thepilot phase,only thosepatientswhowereonARTat thesecentersforatleast6monthswereconsideredforSecondlineART.Theexperiencegainedatthesetwocentersduringthepilotphasewasusedforfurthermodificationandrefinementofprotocols.Currently,SecondlineARTis initiatedat10CentersofExcellence,7PediatricCentersofExcellenceand20ARTpluscenters.AllARTcentersinthecountryarelinkedtotheseCoE/ARTpluscentersandawell-definedreferralprocedureisinplace.



Section I: TECHNICAL GUIDELINES

1.1 First LINE & Second LINE ART REGIMEN:

TheworkingdefinitionofFirstandSecondLineARTRegimenisasfollows:

First-line ART:

First-lineARTisthe initialregimenprescribedforanARTnaïvepatientwhenthepatientfulfillsnationalclinicalandlaboratorycriteriatobeinitiatedonART.

(Current NACO treatment guidelines for First-line ART recommend three drug combination therapy from two classes of ARV drugs for initial treatment i.e. 2 NRTI + 1 NNRTI)

Second-line ART:

Second-lineART is the subsequent regimenused in sequence immediately afterFirst-linetherapyhasfailed.

(Current NACO treatment guidelines recommend use of Ritonavir-boosted protease inhibitors (bPIs) supported by two agents from the NRTI class, of which at least one should be new.

1.2 SUBSTITUTION VS. SWITCH

ChangeofARVsprescribedshouldbecarefullydistinguishedbetweensubstitutingadrugwithinagivenregimenandswitchinganentireARTregimen:

• Treatment Failure refers to the loss of antiviral efficacy to current regimenand it triggerstheSWITCHof theentireregimenfromFirst toSecond line. Itisidentifiedbyclinicaland/orimmunologicalandconfirmedbythevirologicalcriteria.

• SingledrugreplacementofindividualARV(usuallywithinthesameclass)fortoxicity, drug-drug interactions, or intolerance refers to SUBSTITUTION of individual drug andwhich does not indicate a Second line regimen is beingused.


ThefollowingARTregimenshavebeendesignatedas“National ART regimen”byNationalAIDSControlOrganization.(Table1)

Table 1: NACO Approved ART regimen

Regimen ARV Drug Combinations Indications

Regimen IZidovudine+Lamivudine+Nevirapine

FirstlineRegimenforpatientswithHb≥9gm/dlandnotonconcomitant ATT

Regimen I (a)Tenofovir+Lamivudine+Nevirapine

FirstlineRegimenforpatientswithHb<9gm/dlandnotonconcomitant ATT

Regimen IIZidovudine+Lamivudine+Efavirenz

FirstlineRegimenforpatientswithHb≥9gm/dlandonconcomitant ATT

Regimen II (a)Tenofovir+Lamivudine+Efavirenz

FirstlineRegimenforpatientswithHb<9gm/dlandonconcomitant ATT FirstlineforallpatientswithHepatitisBand/orHepatitisCco-infection FirstlineRegimenforpregnantwomen,withnoexposuretosd-NVPinthepast

Regimen IIIZidovudine+Lamivudine+Atazanavir/Ritonavir

RegimenforpatientsonAZTContainingFirstlineregimen,whodeveloptoxicitytobothNVPandEFV

AlsoSecondlineregimenforthosewhoareonTDFcontain-ingFirstlineregimenifHb≥9gm/dl

Regimen III (a)Zidovudine+Lamivudine+Lopinavir/Ritonavir

ForpatientsofRegimenIIIwhodevelopsevereAtazanavirtoxicity

FirstlineregimenforpatientswithHIV-2infectionwithHb≥9 gm/dl

Regimen IVTenofovir+Lamivudine+Atazanavir/Ritonavir

SecondlineregimenforthosewhoareonAZT/d4Tcontain-ingregimenintheFirstline

AlsoforpatientsonTDFcontainingFirstlineregimenwhodeveloptoxicitytobothNVPandEFV

Regimen IV (a)Tenofovir+Lamivudine+Lopinavir/Ritonavir

ForpatientsonRegimenIVwhodevelopsevereAtazanavirtoxicity

FirstlineRegimenforpatientwithHIV2infectionwithHb<9gm/dl

FirstlineRegimenforallwomenexposedtosd-NVPinthepast

Regimen VStavudine+Lamivudine+Atazanavir/Ritonavir

SecondlineforthosewhoareonTDFcontainingregimenintheFirstlineifHb<9gm/dl

Regimen V (a)Stavudine+Lamivudine+Lopinavir/Ritonavir

ForpatientsonRegimenVwhodevelopsevereAtazanavirtoxicity


• PatientsonEFVduetoconcomitantATTneedtobesubstitutedwithNVPtwoweeksaftercompletionofATTorinthenextclinicvisit.NoleadindoseforNVPrequiredinsuchpatients.

• IfNVPisdiscontinuedfor>2weeks,whilere-startingNVP,onehastousealead-indosefor2weeks.

• PatientsonAZTbasedregimentobesubstitutedwithTDF,iftheydevelopanaemia.

• ForpatientswithTDF toxicity,useAZTcontaining regimen ifnotanaemic,d4T ifanaemic(e-approvalfromSACEPrequiredford4Tassupplyofd4Tislimited).

• IfAZT,d4TandTDFcannotbeused,refertoSACEPatCoEonly.Forestablished3TCtoxicity,refertoSACEPatCoEonly.SACEPcantakeadecisiontoprovidealternativedrugandinformNACEPorcanaskNACEP,ifopinionisrequired.

• PatientswhohavedevelopedAZT inducedanaemia in thepast shouldnotbe rechallengedwithAZTagain.

• PatientswhodevelopedsevereNVPhypersensitivity(SJSandTEN)inthepastshouldnotbere-challengedwithNVPagain.

1.3 ALTERNATIVE ARV DRUGS FOR INTOLERANCE TO ZDV/TDF AND NVP/EFV: SUBSTITUTION

SubstitutionofARVdrugsforreasonsof intoleranceortoxicityordrug-druginteractionsmaybeneededinfollowingcases:

Intolerance to both ZDV and TDF:inthiscase,d4Tbasedtreatmentmaybeanalternative(e-approvalfromSACEPrequiredford4Tassupplyofd4Tislimited).

Intolerance to both NVP and EFV:inthiscase,ATV/rasasubstitutionARVwillbeprovideduponreviewandapprovalbytheSACEP.

As per NACO ART Guidelines for Adults and Adolescents, as a general principle, mildtoxicities (grade 1 and 2), do not require discontinuation of ART or drug substitution.Symptomatictreatmentmaybegiven.Moderateorseveretoxicities(grade3and4)mayrequiresubstitutionofthedrugwithanotherARVofthesameclass.(Table2)


Table 2: Major Toxicities caused by First-line ARVs Regimen and recommended drug substitutions

Regimen Toxicity Drug substitution

ZDV/3TC/NVP

ZDVrelatedpersistentGIintoleranceorseverehematologicaltoxicity

NVPrelatedseverehepatotoxicity

NVPrelatedsevererash(butnot life-threatening)

NVP-relatedlifethreateningrash(StevensJohnsonSyndrome,angio-edema)

SubstitutewithTDF

SubstitutewithEFV(exceptinpreg-nancy. Inthissituation,switchtoLPV/r)

SubstitutewithbPIs

ZDV/3TC/EFV ZDVrelatedpersistentGIintoleranceorseverehematologicaltoxicity

EFVrelatedpersistentCNStoxicity

SubstitutewithTDF

SubstitutewithNVP,ifnotonconcom-itantATTorthereisnocontraindica-tiontoNVPuse.bPI(ATV/r)isrecom-mendedinsuchcircumstances

TDF +3TC+NVP/EFV

Usuallywelltolerated

Minor:weaknessandlackofenergy,headache,diarrhea,nausea,vomit-ingandintestinalgas

TDFcanreducebonemineraldensity

Renaldysfunction(Checkurineforroutine/microscopic,bloodurea,creatinineevery6months)

Renaldysfunctionisusuallymild,asymptomatic

Reverseswhenstopmedication

Acute renal failure (rare): reduce dosewhenrenalfailureorifseveretoxicity,substitute

Symptomaticmanagementofminorsideeffects

VitaminD3,Bisphosphonates,andCalciumsupplementsmaybeusedinpatientswithosteoporosis

asperNACOlabmonitoringprotocol

SubstitutewithAZT,ifHb≥9gm/dl;otherwise,substitutewithd4Tfollow-ingreview&e-approvalbySACEP

ATV Indirect hyperbilirubinaemia, clinicaljaundice,prolongedPRinterval-Firstdegree, symptomatic AV block insome patients, hyperglycemia, fatmal distribution, possible increasedbleeding episodes in people withhaemophilia,nephrolithiasis

Seek SACEP/NACEP guidance on substitutionwithLPV/r.


Notes:

• The general principle is that single drug substitution for toxicity should be made within the same ARV class e.g. substitution of TDF with AZT or d4T (for renal toxicity or anemia) or EFV with NVP (for CNS toxicity or in pregnancy).

• d4T should not be a part of HAART for ART naive patients. Patients who are on d4T, substitution should be done with AZT or TDF depending on Hb. Substituting d4T may not reverse lipodystrophy but may slow its progression.

• If a life-threatening toxicity occurs, all ART should be stopped until the toxicity has resolved and a revised regimen commenced when the patient has recovered.

The ‘triple NRTI regimen’ has been shown to be inferior in its outcome and is not used in the National programme

Table 3: Substituting with alternative First Line ARV drugs

First line ARV causing the toxicity Alternative substitute Remarks

(a) Intolerance to both TDF and AZT

PatientshouldhavebeentriedonZDVand TDFwithdocumented intolerancetoboth.d4T+3TCwillbeprovidedafterreviewande-approvalbytheSACEP

TDF + 3TC d4T + 3TC ContinuethesameNNRTI

(eitherNVPorEFV)ZDV + 3TC

(b) For intolerance to both NVP and EFV

PatientshouldhavebeentriedonbothNVPandEFV(exceptforifhistoryofStevenJohn-sonSyndrome,exfoliativedermatitis,erythemamultiformortoxicepidermalnecrolysisispresent)anddocumentedasnottolerating,beforerequiringsubstitutionfortheNNRTIcomponent.NVP or EFV ATV/r ContinuewiththesameNRTIbackbonei.e.

ZDV/3TCorTDF/3TCifnoproblemsEssentially this moves the patient to the PI-based regimen. Counsel for good adherence. If this regimen fails, there is no other optimal alternative regimen at present in the National programme.

These patients should be referred to the SACEP for review, then COE shall manage and provide ATV/r as substitution for intolerance to NNRTI.

(c) Intolerance to TDF, d4T and AZT

RefersuchcasestoSACEPatCoEforreviewandABCbasedARV,ifrequired

See Annex I: Severity grading of clinical and laboratory toxicities of ARVs


1.4 MONITORING PATIENTS ON First LINE ART FOR FAILURE

TheprinciplesofmonitoringpatientonFirstlineARTare:

• Clinical monitoring and stagingateachvisitasperNACOguidelines.

o Doclinical stagingat each visit: use theT staging for clinical events. (seeTable4below)

• Immunological monitoring:Ensuringtheroutinemonitoring labtestsaredoneeg.CD4 countevery6months(orevenearlierdependingonCD4value/clinicaljudgment).

Adherence support and monitoringtoensure>95%adherence:

• Checkforprogressofimprovementateachvisitandweight.

• ScreenforTB:askforsymptomsandsignsofTBe.g.fever,weightloss,nightsweats,haemoptysis,lymphnodesinnecketc.

• Determine if Cotrimoxazole is required or not, based on CD4 counts andWHOClinical staging.

DevelopmentofaneworrecurrentWHOClinicalstage4conditionwhileonARTforatleast6monthsisconsideredfunctionalevidenceoftheprogression of HIV disease.However,certainWHO stage 3 conditions like pulmonary TB and severe bacterial infectionsmaysignify treatment failurewhereascertainWHOstage4conditions likeTB lymphadenitis,uncomplicatedpleuralTB,esophagealcandidiasisandrecurrentbacterialpneumoniasmaynot indicatetreatmentfailurewhichneedstobetaken intoconsideration. If thepatientdoesn’timprovefollowinginstitutionofappropriatetreatmentforthesestage4conditions,theyshouldbepromptlyreferredtoSACEP.(seebelow)

Table 4: Clinical staging events to guide decision making on switching

New or recurrent event on ARTa Recommendations Additional Management Options

Asymptomatic(T1)

DoNotswitch regimen

•Maintainschedulefollow-upvisits, includingCD4monitoring(ifavailable)

•Continuetoofferadherencesupport

Stage2event(T2) DoNotswitch regimenb

•Treatanddmanagestagingevent•Accessandofferadherencesupport•Checkifontreatmentforatleastsixmonths•AssesscontinuationofreintroductionofOIprophylaxis

•ScheduleearliervisitforclinicalreviewandconsiderCD-4(ifavailable)c

Good adherence is the key to maintaining the First line ART for longer duration.

Good adherence is required for Second line ART to ensure viral suppression and increase survival.


New or recurrent event on ARTa Recommendations Additional Management Options

Stage3event(T3) Considerswitching regimenbd

•Treatandmanagestagingeventand monitorresponse

•Assessandofferadherencesupport•Checkifontreatmentforatleastsixmonths•CheckCD4cellcount(ifavailable)cd

•AssesscontinuationofreintroductionofOIprophylaxis

Stage4event(T4) Switchingregimenbe •Treatandmanagestagingeventandmonitorresponse

•Checkifontreatmentforatleastsixmonths•AssesscontinuationofreintroductionofOIprophylaxis

•CheckCD4cellcount(ifavailable)c

•AssessandotheradherencesupportaReferstoclinicalstageswhileonARTforatleastsixmonths(termedT1,T2,T3,T4).

bDifferentiationofopportunisticinfectionsfromimmunereconstitutioninflammatorysyndromeisnecessary.

cTreatandmanagethestagingeventbeforemeasuringCD4cellcount.

dCertainWHOclinicalstage3conditions(e.gpulmonaryTB,severebacterialinfections)maybeindicatorsoftratmentfailureandthusrequireconsiderationofSecond-linetherapy;responsetoappropriatetherapyshouldbeusedtoevaluatetheneedforswitchingoftherapy.

eSomeWHOclinicalstage4conditions(lymphnodeTB,uncomplicatedTBpleuraldisease,oesophagealcandidiasis, recurrentbacterialpneumonia)maynotbeindicatorsoftreatmentfailureandthusdonotrequireconsiderationof Second-line-therapy,responsetoappropriateantimicrobialtherapyshouldbeusedtoevaluatetheneedtoswitchtherapy.

TBcanoccuratanyCD4levelanddoesnotnecessarilyindicateARTfailure.TheresponsetoTBtherapyshouldbeusedtoevaluatetheneedtoswitchARVdrugs.InthecaseofpulmonaryTBandsometypesofextrapulmonaryTB(e.gsimplelymphnodeTBoruncomplicatedpleuraldisease),theresponsetoTBtherapyisoftengoodandthedecisiontoswitchARVdrugscanbepostponedandmonitoringcanbesteppedup.Thisalsoappliesifsevereand/orrecurrentbacterialinfections(asstage3or4events)oroesophagealcandidiasisrespondwelltotherapy.

1.5 IDENTIFYING TREATMENT FAILURE

High index of suspicion is required

LookforthefollowingevidenceofsuspectedtreatmentfailureamongpatientsonFirstlineART(ensurepatienthasbeenonFirstlineARTforatleast6months):

• NewOIs/recurrence/clinicaleventsafter6monthsonFirstlineART(afterrulingoutIRIS).

• ProgressiveCD4countdecline.

• Slow/noclinicalimprovementover6-12months,associatedwithstationaryCD4,despite goodadherence.

• Clinicaldeteriorationinspiteofgoodadherencetotherapy.

* Even though one is less likely to develop IRIS after 6 months of therapy.


TheNACOdefinitionsofARTfailurearelistedintable5below:

Table 5: Definitions of Clinical, Immunological, and Virological treatment failure for First-line regimen.

Clinical failure (i) New or recurrent WHO stage 4 condition, after at least 6 months on ART (ii, iii)

Immunological failure FallofCD4counttopre-therapybaseline(orbelow) 50%fallfromtheon-treatmentpeakvalue(ifknown) PersistentCD4levelsbelow100cells/mm3 (iii,iV)

Virological failure Plasmaviralload>5,000copies/ml3(vi)

Notes:

i. CurrenteventmustbedifferentiatedfromIRIS.

ii. CertainWHOclinicalstage3conditions(egpulmonaryTB,severebacterial infections)mayindicatetreatmentfailureandthusrequireSecondlinetherapyto be considered.

iii. SomeWHOstage4conditions(lymphnodeTB,uncomplicatedTBpleural disease,oesophagealcandidiasis,recurrentbacterialpneumonia)maynot indicatetreatmentfailureandthusSecondlinetherapyneednotbeconsidered.

iv. SomeexpertsconsiderpersistentCD4countsofbelow50cells/mm3 after 12monthsofARTtobemoreappropriate.

v. Switchoftreatmentshouldbedoneonlywhentheviralcountismorethan5,000cells/mm3.

AttheARTcenter,suspicion of treatment failuredependsongoodclinicalassessmentbackedupbyuseofregularCD4counts.Beforelabelingapersonashaving‘failure’–ensurethatthefollowinghasbeendone:

• PatienthadareasonabletrialofFirstlineARTfor(atleast6months)

• Assessadherenceandsupportpatienttoimprovethis(reinforce)

• ScreenandtreatintercurrentOIs,excludeIRIS

• ProvideCotrimoxazolebasedonCD4orclinicalstageimmediately

• IfTBispresent:assessifthisisreinfectionorIRISoranewinfection.IftheresponsetoTBtherapyisgood,thenthedecisiontoswitchtherapycanbepostponedandthepatientre-evaluatedagain.

• CD4count(mostrecent)latestbyamonthaftertreatingtheintercurrentillness,ifany.


The Second line ART will be initiated only at CoE/pCoE/ART plus centers after SACEP review and patients will be transferred back to their referring center after 6 months viral load testing (except those having an OI at 6th month or toxicity to ART drugs).

In order to minimize the unnecessary referral to SACEP, the referring ART centre should follow the following guidelines before referring patients to SACEP:-

1) It is important to differentiate between complications of HIV disease and ARVtoxicitiesasthesemaypresentwithsimilarsignsandsymptoms.

2) The inter-current illnesses likeHepatitis-A,Malaria,etc.mustbekept inmindastheymayalsoleadtosymptomssimilartoARVdrugstoxicities.

3) Toxicitiesduetootherdrugsusedconcurrently likeCotrimoxazole,anti-TBdrugs,other antibiotics, herbalorothermedicationsetc.mustbe ruledoutbefore thetoxicitiesarethoughttobeduetoARV.

4) As a general principle, mild toxicities do not require discontinuation of ART orsubstitutionwithalternativeFirstlinedrugs.Symptomatictreatmentmaybegiveniftoxicityismildandpatientmonitoredclosely.

5) Moderate to severe toxicities require substitutionwith a different drug of sameclasswithadifferenttoxicityprofile.Agradingofcommonlabandclinicaltoxicitiesis at Annex I.

6) Severe life threatening toxicities e.g. Stevens – Johnson syndrome requirediscontinuationofallARVdrugsuntilpatientisstabilized.

7) HistoryandnatureoftoxicitiestoARVdrugsmustbeclearlydocumentedinthepatientrecord,andwherepossibleobjectivegradingoftoxicitiesshouldbedoneaccordingtoAnnexureI.Photodocumentationofskinrash&mucosallesions,lipodystrophyetc.shouldbedoneattheARTCentreandmustbesentduringSACEPreferral.

AllARTcentersshalluseprotocolA1.1listedbelowbeforereferringpatientstotheirlinkedCoE/ARTpluscentreasacaseof“suspectedtreatmentfailure”.


1.6 PROTOCOL FOR DETERMINING ART FAILURE (PROTOCOL A1.1) AT ART CENTERS

‘Suspecttreatmentfailure’duringthemedicalconsultationonfollowingground:

• Clinical:occurrenceofnewOIormalignancy,signifyingclinicaldiseaseprogression;recurrenceofpreviousOI,onsetorrecurrenceofWHOstageIV(&certainstageIII)conditions

• CD4:fallofCD4counttopre-therapybaselinewithoutotherconcomitantinfectiontoexplaintransientCD4countdecrease/50%fallfrom‘on-treatmentpeakvalue’/persistentCD4level<100cells/mm3

• ReviewneedforOIprophylaxis/treatmentespeciallyCPT

• ExplaintopatientaboutsuspicionoftreatmentfailureandneedtorefertoSACEPreview

• Continue1stlineARTwhilewaitingforSACEPreview.

• Refer to SACEP for appointment dates by email (given 2 alternate appointment dates)-informpatientofdateandtoattendSACEPinpersonwithallrecords.

• Sendallpatientinformation/recordstoSACEP/COE/ARTPlusCentre.

• DonotstopFirstlineARTtillvirologicalfailureconfirmedandSecondlineARTstarted.

Workwithpatienttoresolveissuescausingnon-adherence

Continue1stlineART,giveOIprophylaxisifnecessary.

Follow-upmonthly.Reassessclinically.

RepeatCD4after1month(toconfirmvalidityandexcludelabandphysiologicalvariability)

IfCD4notdeclining,continueadherencesupportandrepeatCD4in3months.Reassessanddetermineiftreatmentfailure.

DoesPatientadhereproperlyto1stlineART

SignsorsymptomsofOI

ManageIRISorOI,especiallyTB

Patienthasbeen on ART for at least6months

RepeatCD4immediately

Perform clinical staging

Giveprophylaxisand/ortreatmentforOI

Most recent CD4

within1monthofcurrentmedicalconsultation

available

Ruleoutothercausese.g.IRIS.

Continue1stlineARTandsupportadherence

DoesCD4valueindicate treatment failure?Asper3criteriaabove

YES

NO

NO

NO

NO

YES

YES

YES

YES


Patients who are referred to SACEP for review should be accompanied with complete details of the history and all records, recent CD4 and other baseline tests, photographs of skin/mucosal lesions, if any. Incomplete records will delay decisions to be taken by SACEP. A referral format is enclosed at Annex II

Eligibility for enrollment into Second Line Treatment:

AllpatientswhorequireSecondlineARTshallbereviewedbySACEPatCOE/pCoE/ARTPluscentresasperlaiddownreferralprocedure,irrespectiveofthefactwhethertheystartedtreatmentinprivatesectororNACOcentres.

TheSACEPreviewwillbebasedonthereferralfromtheARTcentreprovidingFirstlineARTtothepatientsuspectedoftreatmentfailure.

Each COE/pCoE/ART Plus Centre will have defined ART centres linked to it and pa-tients fromthesecentres only will be reviewed by a particular CoE/pCoE/ART plus center after proper referral.

Whenapatientissuspectedtohavetreatmentfailure,theARTcentremustfollowtheNACOprotocol1.1)beforereferringtotheSACEP.Thisistoensurethatappropriatereferralsfor‘suspecttreatmentfailure’aremade:

• LaboratorytestsincludingHb,LFT,RFTandCD4andothersymptom-directedtestingshouldbedoneimmediatelyifsuspectedoftreatmentfailure.ThereshouldnotabiggapbetweenthesetestsandSACEPreferral

• MostrecentCD4count(within1month)ofthecurrentmedicalconsultationshouldbeavailable

• In themeanwhile, the patient is to be counseled for 100% adherence in a fewsessions (and/orbeoptionally linked to thenearestCareandsupportCentre foradherencesupport)

• EnsureuseofCotrimoxazoleprophylaxisifCD4<250cell/mm3orbasedonWHOClinical staging

• Continuewiththe1stlineARTregimenduringthistime.

• IfOIoranyintercurrentillnessispresent,treatforthespecificOIs.IftheOItreatmentisnotavailableintheinstitutionthenthesepatientscanbereferredtothenearestGovernmenthospitalorCOE/pCoE/ARTPlusCentreforfurthermanagement.

• CounselandsupportadherenceduringthisperiodofOItreatmentassomepatientsmaynotadheretotakingARTwhentheyfeelill.


• ForsuspectedTB,refertoRNTCPservicesfortreatmentandmonitortheresponsetoTBtherapy.IftheresponsetoTBtherapyisgood,thepatientshouldbeevaluatedagainforsuspicionoftreatmentfailure.RepeatCD4counts2weeksaftertheOIhasbeentreated,andforTB–aftertheintensivephase(i.e.8weeksofATTcompleted).Reviewthepatientforsuspectedtreatmentfailureasperprotocol.

If protocol 1.1 points towards a suspected treatment failure, following steps need to be taken:

• The referring ART centrewill inform and counsel the patient on the findings of‘suspected treatment failure’, support psychosocial needs, counsel to continue1st lineARTuntilotherwiseadvisedbytheARTSMO/MO;andwiththe informedconsentofthepatientforsharedconfidentialityinitiatetheprocessforreferraltotheSACEPforCOE/pCoE/ARTPlusCentres.

• During counseling/while referring, never tell the patient that his First line has failed until viral load report is available as failed. Counsel about suspicion of failure and that he is being referred for opinion and confirmation.

• TheARTcenterwill sendtherequest formwiththefilleddetails togetherwithaconfirmedcontactphoneofthepatient;andphotocopiesofthecasesheets/patienttreatmentrecordtotheCOE/ARTPlusCentrebye-mail.

• TheCoE/ARTplus centrewill enter thepatientdetails in the SACEP register andreviewthereferralformwithotherclinicaldetails.

• After review of patient records by the SACEP coordinator/research fellow/SMO,if the SACEP at CoE/pCoE/ART plus centre considers that the patient should bereviewedbySACEPthentwoalternativeappointmentdatesaregivenbye-mailtothereferringcentrewhowillinformthepatient.

• Afterreviewandothernecessary investigationsbytheSACEP,theCoE/pCoE/ARTplus centrewill send the feedback form (lower half of the referral form) to thereferringcentreandinformthemaboutthefinaldecisionoftheSACEP.

• Ifthepatientistobestartedon2ndlineART,theCoE/pCoE/ARTpluscentrewillaskthereferringcentretotransferoutthepatienttothatparticularCoE/pCoE/ARTpluscentreandpatientmaybesentbackbefore6month(maybeat3month)toNodalARTCentreonrequest,ifclinicallystableandimproving


1.7 MANAGEMENT PROTOCOL BASED ON SACEP DECISION AND VIRAL LOAD TEST RESULTS

OncepatienthasbeenreferredtoSACEPforevaluationaccordingtothetechnicalprotocol(A1.2),theSACEPwillreviewthepatientwithhisrecordanddocumentitsdecision,whichcan be

o Provide2nd line ART

o Not eligible for 2nd line ART

o ContinueFirstline,reinforceadherenceandre-evaluate

o EvaluateforHIV2

AfterthedecisionoftheSACEPtoprovide2nd lineARTtothepatient,theCOEstaffwillensurethenecessaryworktopreparethepatientforinitiationofSecondlineART.

TheSACEPcoordinator/DataManagershallcommunicatethedecisionoftheSACEPtothereferringARTcentrefortheirreference,andARTcentreto‘transferout’thepatienttoCOE/pCoE/ARTplusCentre.(SeeM&Esection).Thecentershallensurebaselinelaboratoryandclinicalscreening isdoneandrecordedbefore initiationofSecond lineART.AsapartofTreatmentpreparedness,thepatientshouldundergoaminimum of 3 counseling sessions. Treatment supporter should ideally be present. Consent form for 2nd line ART initiation shouldbesignedbythepatient–ANNEX III

The CoE/pCoE/ART plus center shall also ensure linkage with NGO/CBO/FBO/positivenetwork/CareandSupportCentre/ICTCforoutreachandcommunity/homebasedcare

Only the Programme Director/nodal officer of the COE/pCoE/ART plus Centre are authorized to prescribe Second-line ARVsafterapprovalofSACEP.ThedecisiontoswitchfromFirstlinetoSecondlinetherapyresidesonthedecisionoftheSACEPwhichwillmeeteveryTuesday(orthedesignateddayofthecentre),toreviewthecasehistory,ordertheViralloadtestingandapproveinitiationofSecondlineARTfortreatmentfailureanduseofalternativeregimens.

DetailsinthereportingandrecordingformatsshouldbecompletedbytheCOE/ARTplusCentre staff so that good documentation is present. Thiswill enable the COE/ART plusCentreandthenationalprogrammetolearnfromthenationalrolloutofSecondlineART.

Routinedrug resistance testing isnotpartof thenationalprotocol for Second-lineART,howeveritmaybedoneforresearch/surveillanceandmonitoringpurposes.Bloodsampleson dried blood spots (DBS)shallbecollectedandstoredforuseata laterdatefordrugresistancegenotyping.(SeeLaboratoryguidelinessectionbelow)


Suspect treatment failure by clinical and/or CD4 criteria

(Exclude other factors: poor adherence, intercurrent illness, TB, OIs, IRIS etc.)

In 5-10% of the patients, there may be discordance between the Viral load and the clinical assessment/CD4.

Ithasbeennotedinsomecases,VL<400copies/mlorVLis400-5,000copies/mlbutthepatientshaveclinicaleventsandCD4isdecreasing.SuchcasesshouldbedocumentedandsenttoNACOforexpertopinion(NACEP).

Reviewpatientclinically.Continue1st line ART

InvestigateforothercausesforclinicalsignsorCD4fall.

EvaluateforOI/IRIS/non-HIVrelatedconditions

Reinforceadherenceto1st line ART.

“Transferout”fromreferringcentertoCoE/pCoE/ARTpluscenter

Counselpatientfor2nd line ART (minimum 3 sittings)preparednessandadherence.

ScreenforOIs/TB.

Givecotrimoxazoleifrequired.

Investigateandcorrectanaemia.

Initiate2ndlineARTwhenpatientisprepared.

VL<400

Transfer back to original (referring) ARTcenterwithtreatmentplan,oncase-to-casebasisdependingoncapacityofreferring ART centre

IfVL>400withnoOI,stilltransferthepatientbacktothereferring centre andcallthepatientbackforVLtestingafternext6monthsorelseretainthepatient,ifrequired

VL > 400

SACEPreferspatientbackto original ART center withappointmentdatefornext evaluation/VL test at 6 months withwrittentreatmentplanandfeedbackform.

Monthlyfollow-upatARTcentre.

Reinforceadherence

Strict CD4 follow-up3 monthly to monitor CD4 trend and if CD4 criteria forfailureisnotthereCD4followupisenough.

Counselpositiveprevention,condomuseandnutrition

ContinueARTatreferring (original) ART Centre

RepeatCD4andVLin3monthsthenSACEPreview

Counselpositiveprevention,condom usage and nutrition

VL < 400 copies/ml

VL >5,000 Copies/ml

VL 400 – 5,000 Copies/ml

FU at COE/pCoE/ART Plus Centre for at least 6 monthstostabilizepatientandadherenceto2nd lineART,reviewthe6-monthVL

Counselpositiveprevention,condomuseandnutrition

Protocol A1.2: SACEP Management according to viral load results

VLafter6months ofIIndlinetherapy

Nochangein1st line ART

Virologicallyconfirmedtreatmentfailure.Switchto2nd line ART regimen

Nochangein1st line ART

Viral load test


1.8 INITIATING THE STANDARDIZED NACO SECOND-LINE REGIMEN

AftertheSACEPhasapprovedSecondlineARTforthepatient,theclinicalmanagementshallbetheresponsibilityoftheCOE/pCoE/ARTPlusCentreandthepatientwillbe‘Transferredout’fromthereferringARTcentretotheCOE/pCoE/ARTPlusCentre.

TheobjectiveoftheSecond-lineis:

• ToprolongsurvivalofthePLHIV

The NACO standard Second line regimen (TDF + 3TC + ATV/r) (for those on AZT/d4T in First line regimen) aims to achieve viral suppression for as long as possible, so that survival can be prolonged.

Under thepublic health settings in India, theobjectiveof the Second-line is toprolongsurvivalofthePLHIVratherthanacompleteviralsuppressionas indevelopedcountrieswheremultipleSecondlineoptionsandsalvageregimenareavailableandearlyswitchingisthenorm.TheNACOtechnicalresourcegrouponARThadextensivediscussionsontheregimenwhichisoptimumforthenationalsettingandon‘early’vs‘late’switchingaswell.SincewehadonlyoneSecondlineregimenwithnosalvageregimen,itwasdecidedtogoforlateswitchingtogivethebenefitofFirstlineARTforaslongaspossible.

Table 6: NACO Second Line Regimen:

ARV drugs for 2nd line

Dosage Dosing schedule

TDF + 3TC Fixeddosecombinationof

Tenofovir300mg+Lamivudine 300 mg

oncedailyintabletform

Please advise thepatients toconsume all the three pillssimultaneously after meal(preferablydinner).(Keepthedruginteractionsinmind)

ATV/r Tab.Atazanavir300mg,Tab.Ritona-vir100mg

Eachtabtobetakenoncedailysimultaneously

The major side effects of Second line ART are described below in Table 7.


Table 7: Side effects related to the NACO Second Line Regimen:

ARV drug Side effect/toxicity Management

TDF Usually well tolerated

Minor:weaknessandlackofenergy,headache,diarrhea,nausea,vomitingandintestinalgas.

Moreserioussideeffectsincludeliveror kidneyfailureandpancreasdisease.

TDFcanreducebonemineraldensity

Symptomaticmanagementof minorsideeffects

MonitorLiverandRenalfunctiontestasperNACOlabmonitoringprotocol

Calciumsupplementsmaybeusedinpatientswithosteoporosis

ATV* ApartfromthePI-classspecificside-effectslikehyperglycemia, fat maldistribution, hyperlipi-daemia(especiallywithRitonavirboosting),in-creasedbleedingepisodesinhemophiliacsetc.the unique side-effects of Atazanavir includeindirecthyperbilirubinaemia(producingyellowdiscoloration of eyes), skin rash and nephroli-thiasis(rare).

Unique drug interaction involving Atazanavir:

InadditiontoallthedruginteractionsinvolvingPIclass,Atazanavir hassignificantdruginterac-tionwithantacids,H2Receptorantagonistsandprotonpumpinhibitors*

Thepatientsneedtobecounselledthattheymayappeartobejaun-dicedwithyelloweyesbuttheyshouldnotbeafraidasitwillbeacosmeticproblemonly(likeGilbertdisease).Itshouldnotbetakenashepatotoxicity.However,LFThastobedoneshouldsomeoneappearstohavejaundice.Also,theyshouldbeadvisedtoconsumeplentyofwater.

Antacid:GiveAtazanaviratleast 2hoursbeforeor1hourafter antacidsoranybufferedmedications.

LPV/r Sideeffectsincludeabdominalpain,abnormalstoolsorbowlmovements,diarrhea,feelingweak/tired,headacheandnausea.Inaddition,patientstakingLopinavirshouldbemonitoredforpossibleliverproblems.Peopletakingthedrugwhohaveliverdisease,suchashepatitisBorhepatitisC,mayexperienceaworseningoftheirlivercondition.Asmallnumberofpa-tientshaveexperiencedsevereliverproblems.

Symptomaticmanagementofminorsideeffects.

SupportivecounselinganduseofotherdrugstomanageGIeffectsshouldbedone.Thesesymptomsimproveafterafewweeks.

MonitorLFTs,Lipidprofileandbloodsugarregularly

3TC Usually well tolerated

Sideeffectsmayincludecough,diarrhea, dizziness,headache,lossofappetite,mildstomachcrampsorpainandtroublesleeping.

Moreserioussideeffectsincludeburning,tingling,orpaininthehands,arms,feet,orlegs;chills;ear,nose,orthroatproblems;fever;muscleaches;nausea;paleskin;severestomachpain;skinrash;unusualtirednessorweakness;vomiting;andyelloweyesorskin.

Symptomaticmanagementof minorsideeffects


CAUTION : (WE SHOULD BE CAUTIOUS IN RECOMMENDING THE USE OF H2RA & PPIs WITH ATV/r AS MOST OF OUR PATIENTS ARE ARV-EXPERIENCED; THIS IS A BLACK BOX WARNING FOR ATV; ONLY SYSTEMIC ANTACIDS CAN BE CO-PRESCRIBED)

Side-effects of Atazanavir:ApartfromthePI-classspecificside-effectslikehyperglycaemia,fatmaldistribution,hyperlipidaemia(especiallywithRitonavirboosting);theuniqueside-effectsofAtazanavirincludeindirect hyperbilirubinaemia (producing yellow discolouration of eyes),skinrash,prolongationofPRintervalandnephrolithiasis.

1.9 DRUG INTERACTION:

Avoid concurrent use of the following drugs:

Astemizole, Cisapride, Fluticasone, Indinavir, Lovastatin, Simvastatin, Midazolam,Terfenadineetc

Unique drug interaction involving Atazanavir:

In addition toall thedrug interactions involvingPI class,Atazanavir has significantdruginteractionwithantacids,H2Receptorantagonistsandprotonpumpinhibitors.

S NoPatient on following drugs concomitantly

Recommendation/points to remember for ATV

1 Antacids GiveATVatleast2hoursbeforeor1hourafterantac-idsorbufferedmedications

2 H2ReceptorAntagonist 1. H2 receptor antagonist dose should not exceed adose equivalent to Famotidine 40mgBID inART-naïvepatientsor20mgBIDinART-experiencedpa-tients.

2. GiveATV300mg+RTV100mgsimultaneouslywithand/or>10hoursaftertheH2receptorantagonist.

Example: If a PLHIV on Zidovudine + Lamivudine + Ata-zanavir/Ritonavir (Regimen IV) requires to be treated with Famotidine 20 mg BID or Ranitidine 150 mg BID, S/he should be instructed to take Tab. Famotidine/Ra-nitidine with Zidovudine + Lamivudine at 8.00 AM and in evening give ZL and ATV/r at 8 p.m. and ensure that there is a gap of at least 2 hours before or 1 hour after Famotidine/Ranitidine evening dose.


S NoPatient on following drugs concomitantly

Recommendation/points to remember for ATV

3 ProtonpumpInhibitor 1. H2 receptor antagonist is not recommended with Tenofovir+Lamivudine+Atazanavir/Ritonavir

2. PPIs should not exceed the dose of Omeprazole20mg daily or equivalent dose of Esomeprazole20mg/Pantoprazole40mg/Rabeprazole20mg inPI-naïve patients, along with Ritonavir boostedAtazanavir.PPIsshouldbeadministeredatleast12hourspriorto Atazanavir/Ritonavir.

3. PPIs are not recommended in PI-experienced patients.

Example: If a PLHIV is on Tenofovir + Lamivudine + Atazanavir/Ritonavir requires to be treated with PPI, S/he should be instructed to take Tab. Omeprazole 20 mg/Esomeprazole 20mg/Pantoprazole 40 mg/Rabe-prazole 20 mg OD at 8 AM and Tenofovir + Lamivudine + Atazanavir/Ritonavir after 8 PM.

a. Prolongation of P-R and Q-Tc interval in the ECG can occur. So PR interval needs to be monitored in patients with known conduction defects or with concurrent use of other drugs that alter conduction abnormalities (like diltiazem, clarithromycin, cisapride, ketoconazole etc.). However, routine ECG before starting Atazanavir based ART is not mandatory.

b. Atazanavir induced urolithiasis is also reported; presumably due to precipitation of the drug resulting in crystalluria in a manner analogus to Indinavir.

c. If the serum total Bilirubin is > 7 mg/dl or the Child-Pugh Score is ≥ 7, then ATV/Ritonavir cannot be used and the details of such cases should be mailed to National AIDS Clinical Expert Panel (NACEP).

Counseling issues:

ThereisaneedforenhancedcounselingofthePLHIVontheseregimensparticularlyuniquesideeffectsofAtazanavir/Ritonavir.

So,thepatientsneedtobecounseledthattheymayappeartobejaundicedwithyelloweyesbuttheyshouldnotbeafraidasitisonlyacosmeticproblem.Itshouldnotbetakenashepatotoxicity.However,LFThastobedoneshouldsomeoneappearstohavejaundice.Also,theyshouldbeadvisedtoconsumeplentyofwater.


AsweareusingtheATVandRTVasseparatepills,duringcounselingweneedtoimpressupon thepatients to takeboth thepills togetherasourpatientsaregoing to takeATV,RTValongwithTDF,iftheymissRTV,thentherewillbedecreasedATVbloodlevelanditmayleadtotreatmentfailure.Soduringthecounselingsession,thesepointsneedtobestressedadequately.TheyshouldalsobecounselledthatATV/rshouldalwaysbetakenonafullstomachasotherwisetheabsorptionofATVgoesdown.

AlltheNodalOfficers,SMOs&MOsarerequestedtosensitizethecounselors,pharmacists,nurseandotherARTCentrestaffonuseofAtazanavir/Ritonavir.

Important consideration in pregnancy

RitonavirboosterLopinavir(notATV)istobeusedforpregnantwomenexposedtosd-NVPinthepast

1.10 SECOND-LINE ART AND TB TREATMENT

TuberculosisisthemostcommonlydetectedseriousopportunisticinfectionamongPLHIVsinIndia.Whiletuberculosishastobetreatedappropriatelyandonpriority,inthecontextof Second-line ART drug-drug interactionsmust to be considered. Rifampicin alters themetabolismofProteaseInhibitors,includingLopinavir,AtazanavirandRitonavir,andreduceseffectivenessof standarddoses.However,Rifamycin-classdrugsarehighlyefficacious intreatment of tuberculosis. Annex V

AnotherRifamycin,Rifabutin,canbeadministeredinthepresenceofPI-containingSecondlineARTregimenwithoutcompromisingtheefficacyofARTorAntiTBtreatment.ThereforeNACPandRNTCPhaverecommendedthesubstitutionofRifabutinforRifampicinforthedurationofTBtreatment.InthepresenceoftheboostingdruglikeRitonavir(PI),Rifabutinmetabolism is altered, and less Rifabutin is needed than would be without Ritonavir.Therefore, the dosage of Rifabutin during the administration of Second line regimencontainingLPV/rshallbe150mgthriceweeklyforallpatients,weighing>30kgweight.TheremainderoftheTBtreatmentregimens,includingdosingandduration,remainunchangedasperRNTCPguidelines.

Aswithallanti-TBtreatment,supervised treatment under DOTS is required.Thepatients’DOTSprovidershouldbeinformedandcounseledregardingthesubstitutionusingRifabutin,bythetreatingmedicalofficer.

Rifabutin dose: 150 mg OD, three times a week

SomeofthecommonsideeffectsofRifabutinincludeorange-browndiscolorationofskin,tears,saliva,sweat,urine,andstoolsandwillstopwhenyoufinishtakingRifabutin.TheARTcentreSMO/MOshouldbecontactedincaseofh/ochestpain,muscleaches,severeheadache, fatigue, sore throat, flu-like symptoms, vision changes, unusual bruising orbleeding,nausea/vomiting,yellowingoftheskinoreyes.


Initiation of 2nd line ART in patient already on anti-TB treatment

Ifapatientisalreadyonanti-TBtreatment,andneedstobeinitiatedonSecond-lineART,thensubstitute Rifabutin for Rifampicin within the RNTCP regimen for 2 weeks prior to initiation of Second-line ART.Thisistoallowhepaticmetabolism(inducedbyRifampicin)tonormalizepriorto initiationofPI-containingregimens.Whilethepatient iscounseledandpreparedforinitiationof2ndlineregimen,thepatientshouldstillbegiventhe1st line ARTregimen.ThereisnoneedtoincreasethedoseofEFVwithRifabutincontainingATT

RNTCP recording and reporting:TBtreatmentcategorizationdoesnotchangewiththeuseofRifabutin,whichisasimplesubstitutionforRifampicin.ThesubstitutionofRifabutinforRifampicinshouldbenotedontheTBtreatmentcard,andintheTBregister“Remarks”column.

Initiation of Anti-TB treatment in patients already on 2nd line ART

Ifthepatientisalreadyon2ndlineART(Atazanavir/Ritonavircontainingtreatmentprotocol),anddetectedtohaveTB,subsitute Rifabutin for RifamipicinwithinthecategoryIorIIanti-TBregimenfromthestartofTBtreatment.

InregardstotheavailabiltyofRifabutinattheDOTScentresajointletterhasbeenissuedbyDDG(TB)andDDG(NACO)dated,19thFeb2013.TheletterisenclosedatAnnexX.

Initiation of Second line ART/Anti TB Treatment in the presence of TB co-infection (Protocol A 1. 3)

PLHIV on 1stlineARTreviewedbySACEP,hastreatment failure and eligible for 2nd line ART

SubstitutewithRifabutinforRifampicin,withintheanti-TBtreatmentregimen

•Treatmentpreparedness&counseling

•InitiateRifabutincontainingAnti-TBregimenonpriority

•Treatmentpreparedness&counseling

•InitiateRifabutincontainingAnti-TBregimenonpriority

•Initiate2nd line ART regimen whenpatientisstabilizedonTBtreatmentafter2weeks

•Treatmentpreparedness& counseling

•Initiate2nd line ART

AlreadyoncategoryIorIIAnti-TBtreatmentWithorwithoutEFV-basedARTregimen

Needtoinitiate2ndlineARTwithconcurrentdetectionofTBco-infection

Patientalreadyon2ndlineandthendetectedtohaveTBco-infection

After 2 weeks of Rifabutina

Note:

aThe2weekperiodallowshepaticfunctiontonormalizeafterinductionofP450cytochromeenzymes byRifampicin

bPatienttobecounseledwellforbothanti-TBand2ndlineART.Pillburdenishigh.Ifpatientisnotstartedon2nd lineARTimmediately,thencontinue1stlineregimentillpatientisswitchedtoswitchto2nd line ART occurs.


1.11 LABORATORY MONITORING OF PATIENTS ON SECOND LINE REGIMEN

TheprotocolforlaboratorymonitoringofpatientsonSecondlineARTisdescribedintable9below

Table 9: Protocol for laboratory monitoring of patients on Second line ART

TestsBase-line0

3 6 12 18 24

Hb, CBC Then annually

LFT

Renal function test Then every 6 -monthly

Fasting blood sugar Then annually

Fasting lipid profile

Viral Load (VL) Then no more VL unless indicated in protocol A1.2

CD4

More frequently if required.

Note: Resistance testing is for operational research/surveillance/monitoring only, undercurrentnationalprogramme.

Abaselineandannualcheckupoffastingbloodsugarandlipidprofileisrecommended.Thisistounderstandthebaselineandmonitorthepossiblemorbidities/sideeffectsofPIs.However,thenationalprogrammewillnotbeprovidingstatinsorfibratesfortreatmentofdyslipidemia.

1.12 ADHERENCE AND SECOND-LINE ART

NACO 2008 tools to support counseling and treatment adherenceforallpatientsandespeciallyforpatientswhohavedifficultywiththeirFirstlineARTandthosetakingSecond line ART:

1. Patientcounselingdiary(individual)

2. UsetheVisualAnalogueScale(VAS)tohelpunderstanddrugadherence

3. Patienteducationinformationleafletsfortheirprescribedregimens

4. Patientpill-takingmonthlycalendar

Long termadherence continues to be challenge to PLHIV taking lifelongART. Themostcommon reason for HIV drug resistance is due to non-adherence and missed doses.Adherenceapproaching100%isrequiredforoptimalviralsuppressionbothinFirstlineandSecond line ART.


Theexperienceofthenationalprogrammetodateisthatingeneral,socio-demographiccharacteristicssuchasage,sex,socialclass,maritalstatusorpersonalitytraits,race,religionandeducationallevelsarepoorpredictorsofadherence.Patients’beliefs,knowledgeandexpectations (sometimes shared by friends and community), strongly influencemedicaldecision-making and willingness to begin and then adhere to prescribed treatments.Adherence is found to be greater when the person perceives the need for treatment,believes thetreatmentwillbehelpfulandunderstands thepurposeof themedications.Attitudesoffriends,trust inphysiciansandconfidenceinone’sownabilitytofollowtheagreed-upontreatmentsarealsoassociatedwithadherence.Lackofbeliefintheefficacyoftreatmentmayleadtoeithertreatmentrefusal,orinadequateadherenceonceinitiated.

Itisforthisreasonthatthe initial detailed counseling by the doctor about combination therapyiscrucialforlatersuccess.Simplytellingthepatientthatit’stimetobeginantiviraltherapy,writingoutprescriptionsandhandingthemtoapatientwhoasksnoquestionsandexpressesnoopinionsislikelytoleadtoadherenceproblemsandtreatmentfailure.Occasionally,well-meaningphysiciansurgereluctantpatientstostart treatment,despitethepatients’reservations.Themoreassertivepatientmaystatethatheorsheisnotreadytostart,butothersmayacquiescetoaregimenthattheyconsiderofdoubtfulvalueornotcompatiblewiththeirlifecircumstances.Do not start Second line ART if the patient is not ready to comply with adherence and follow up schedule.

HIV/AIDSisassociatedwithneurocognitive problemssuchasmemoryloss.Thiswillcauseadherence problems. Some patientsmay have trouble sorting their pills for the day ortheweek,whileothersmayhavetroublekeepingtrackofthetime,ormaysimplyforget.Evenamongasymptomaticpatients,memoryproblemsarepresent.Whenmemory isasignificantproblem,prescriptionofcomplexmedicalregimensisunlikelytosucceedunlesssocial(e.g.,familymember)orinstitutional(e.g.,homeattendant)resourcesareregularlyavailabletohelpwiththeschedulingandtakingofmedications.

Psychiatric disordersalsomayconstitutebarrierstoadherence.Evenmildconditionssuchasdepressedmood,aselicitedonself-reportratingscales,maybeassociatedwithmedicationnon-adherence,eitherbecauseofimpairedconcentration,whichisoneofthecriteriafordiagnosingmooddisorders, or becauseof feelings of hopelessness anddespair. Amongthose with chronic and severe psychiatric disorders, noncompliance with psychotropicmedication often contributes to relapse.When substance abuse is also present in HIV-infectedpatientswithseverementalillness,manyofwhomlivealoneinunstablehousing,theprobabilityofeffectivemanagementofcombinationtherapyispoor.

Two-waycommunicationbetweentheclinical teamandpatient iscritical to thesuccessofadherence.The patient has to believe that combination therapy will make a profound difference in extending life, or else the regimen’s burdens will outweigh the perceived rewards.Initiatingcombinationtherapyisnotusuallyregardedasanimmediateneed.Ifit takesextratime,oradditionalvisits, fortheclinical teamtoconvincethepatientthatcombination therapy shouldbe initiatednow,or for thepatient to convince thedoctorthathisorhercurrent lifecircumstancesaresimplynotconducivetostartingnow,thenextratimemustbeprovided.However,thereareafewurgentsituationswhenimmediateinitiation may be considered imperative. One example is a patient with an essentiallyuntreatableconditionsuchasPMLwho is rapidlygettingsicker. In thesecases,ARTcanleadtolife-savingremission.Inlessurgentsituations,treatmentcanbesafelyputoffwhiledoctor-patientdiscussionscontinue.


Attheoutset,beforeevenbeginningcombinationtherapy,itishelpfultoreview anticipated problems and barriers to adherence, which then permits the patient to work out solutions on his or her own or with assistance.Forthispurpose,someprovidersgivetheirpatients1-2 weeks of cotrimoxazole and to use this time to reinforce adherence.Which dosesareproblematic?Whatarethecircumstances?What isthepatientthinkingwhenerrorsoccur?Whatisthepatient’sattitudeaboutmistakes?Doesheconsiderafifteen-minutedelayacatastrophesignifyingirremediablefailure?Alternatively,whatdotheythinkaboutmissingaweekend’sworthof“medications”?Suchrehearsalisoftenextremelyhelpfulinanticipatingandcorrectingpotentialpitfalls.

Somepatientsfindithelpfultohaveawritten treatment planthatshowsthenameofthemedication,timeofeachdose,numberofpillsorcapsulesperdoseandmealrestrictions,ifany,alongwithatelephonenumbertocallwithquestionsandforthenextappointmentdate.Bothdoctorandpatientshouldkeepacopyoftheplanforreviewatthenextvisit.Othertechniquesforpromotingadherenceincludeidentifyingdailyactivitiesthatcanbelinkedtopill-taking(e.g.,aregularTVshow),keepingamedicationdiaryorlog(preprintedformscanbeprepared),preparingpillsfortheweekatfixedtimes(e.g.,Sundayevening),andotherwiserelatingpill-takingtothenormalrhythmsofdaily life.Planningaheadforchangesinroutineorforweekendscanforestalllapsesatsuchtimes.

Mechanical aids are often useful. These range from pill boxes with dividers in whichmedicationscanbesortedbytheweekandtimeofdaytotimers,alarms,beepersthatcanbesettoringwhenitistimetotakepills,tosignsandchecklistspostedonrefrigerators.

Socialassistancecanmakeamajordifference,especiallyatthebeginningoftheregimen.Somepeoplehaveafamily member/treatment supporterwhoagreestoprovidereminderseverytimemedication isscheduled.Childrenremindtheirmothers;sometimesmothersremindtheiradultchildren.

Overtime,initialenthusiasmcandwindleastheincessantdemandsofschedulingpersist.Aspeoplefeelbetterandreturntowork,newproblemsarise.Amongthesearemaintainingconfidentiality, arranging schedules to accommodate pill-taking, frequent trips to thebathroom (if takingmedication that requires a high liquid intake), occasional dayswithsignificantsideeffectssuchasdiarrhoea,theconstantreminderofillnessandsimplytheongoingburdenoftheregimen.Itisimportanttoknowinmoredetailaboutthehurdles,questionsandworriesthatariseovertimewithART,andaccordinglytodevelopindividual interventionstomaintainadherenceoncetherapyisestablished.

ForpatientswhohavedifficultieswithadherencetoFirstlineARTorwhoaresuspectedoftreatmentfailure,orwhowillstartSecondlineART,the objectives of adherence counseling are:

• ToimprovetheadherencetomedicationssothatARTissuccessful

• To encourage self management of medications

• To foster honest communicationbetweenproviderandpatient

• To respect patient choices and decision-making related to their HIV relatedmedical care

Patients don’t want to disappoint their health care provider. The challenge is: how do you make it okay to say ‘no’ to doctors/counselors/nurses; or make it okay to say ‘I can’t do this’



Section II: OPERATIONAL GUIDELINES

2.1 STATE AIDS CLINICAL EXPERT PANEL (SACEP)

a. StateAIDSClinicalExpertPanels(SACEP)havebeenconstitutedatallCOEsandARTpluscentretoreviewthepatientsreferredtothemwithneedforalternativeFirstlineandSecondlineART.EachCOE/ARTpluscentrehasARTcentreslinkedtoitandpatientfromthesecentersonlywillbereviewedbyaparticularCOE/ARTpluscentre.

b. TheSACEPwillreviewthepatientandhis/herrecordsandwillapprovetheCOE/ART plus to provide PI based Alternate First line drugs if the patient is foundtohaveseveretoxicitiestotheFirst lineARTorSecondlineARTasperclinicalprotocols.

c. OncethedecisionismadebySACEPtoprovidealternativeFirstlineARTtothepatientreviewed,patientswhoarerecommendedforPIbasedalternateFirstlineare‘transferredout’totheCoE/ARTpluscentrefromthereferringcentre.

d. ThepatientshallbestartedalternativeFirst/SecondlineARTonlyafteradherencecounselinghasbeendoneandpatienthasbeenassessedtobepreparedfor100%adherencetotheregimen.

e. Patients who have not been found eligible for Second line ART afterSACEP review a detailed follow up plan should be given to the referringARTcentreinthereplybackform.

State AIDS Clinical Expert Panel (SACEP) havebeenestablishedateachcentreofexcellence/pCoE/ARTpluscentre.Itconsistsof:

1. ProgramDirector/DeputyProgramDirectorofCOE/pCoE,NodalOfficerofARTpluscentre

2. OnemoreARTexpert(preferablynotfromthesameARTcentre)-PaneltobeformedbyNACO

3. RegionalCoordinator/JointDirector(CST)/Consultant(CST)atSACS/DPM.

Inadditiontotheabove,therewouldbeobserversfromcentral levelregularlyformonitoringpurposes.


The Terms of reference of SACEP/are:

• ReviewanddecideonallcasesreferredbythereferringARTcentreforPIbasedalternateFirstline/Second-lineARTprovision–bothforeligibilityforViralloadtestingandstartingSecondlineoralternativeFirst-lineARTregimen

• MeetattheCOE/ARTpluscentretoreviewcaseseveryTuesday(oraprefixedday)(nextworkingdayincaseofaholiday).Thisistoensurethatthereisnodelayinreviewandprocessingofthecasereferredforreviewofsuspectedtreatmentfailure.Amaximumof15-20patientsshallbereviewedateachmeeting(oldandnew).Howeverifthereare too fewpatients, themeetingmaybedeferredto thenextweek. If thenumberofpatientsonnextweekisagaintoosmall,themeetingstillshouldbeheldtoavoiddelay. It shouldbeensured that there isminimumtimetaken for reviewofpatientsandprovisionofdrugs.Alleffortsshouldbemadetoensurethatthisperioddoesnotexceedfourweeks.

• MentoringandensurehighqualitycasemanagementofthePLHAonSecond-lineARTbythereferringARTcentre

• DocumenttheregistrationandmonitorprogressofallpatientssuspectedoftreatmentfailuresentforSACEP/review

The SACEPwill follow the technical protocols as laid out byNACO in section I of theseguidelines.

Howeverforalltechnicalissues,theARTpluscentrescanreferdifficultcasestoSACEPoftheirCoE intheir region.Forpatientsrequiringanyfurthertechnical/operationalclarification,COE/ART plus centres can refer cases toNACEP (National AIDS Clinical Expert Panel) [email protected] and [email protected] coordinatedbyDrBBRewari,NPO (ART). Thispanel canhave representatives fromTRG,institutionsorindependentexpertsthatwouldbedeemedmostappropriateforthequeryunderconsideration.Hence,thecompositionoftheNACEPwillbedynamicanditscompositionwillvarydependingonthetypeoftechnicalquery.ThiswillensurethatmostappropriateresponseandguidanceisprovidedforthequerybythevarietyofexpertsandexpertiseonvariousareasundertreatmentandcareforHIV.


Referral to SACEP

OnceapatientonART is suspected tohave toxicity toanyARVor is suspected tohavetreatmentfailure,theARTcentreSMO/MOshouldfollowthestepsmentionedbelow:

Step1 • The referringART centre should go through sectionon “Suspecting drugtoxicitiesamongpatientsonFirstlinetherapy”/Suspectedtreatmentfailure(Protocol A1.1).

• GothroughthetoxicitiesgradinginARTguidelines.

• ReferringARTcenterwillsendphotocopiesofpatient’srecordsandphotodocumentationfortypeoftoxicitiestoSACEPcoordinatoratCoE/ARTpluscentretogetherwithReferral/ReplyForm(Annex II) andconfirmthatSACEPcoordinatorhasreceivedit.

Step2 SACEPcoordinator/COEresearchassociatewillFirstenterthepatientdetailsintheSACEPregisterandthengetthepatientshistoryreviewedandifeligiblegiveappointmentdate/time(2alternativedates)tothereferringcentrebye-mail.

BeforegivingappointmenttheCoE/ARTpluscentremayrequestforanyotherpatienttreatmentrelateddocuments.

Step3 The referringARTcenterwill thencommunicate thedate/time topatientbyphone/personalcontactbyORW

Step4 OnlyaftertheSACEPhasreviewedthepatientandrecommendedinitiationofSecondline/AlternateFirstlineART(PIbased),initsreplyform,willthepatientbe‘transferredout’totheCoE/ARTpluscentre.

Note: For alternate First line ART:onlythosepatientswouldbe‘transferredout’toCoE/ARTplus centrewhoarebeing initiatedonPIbasedalternateFirst lineART. ForotherpatientsforwhomsubstitutionisbeingdonewithinNNRTIorNRTIclassofdrugsno‘transferout’isrequiredandtreatmentcanbechangedatthatARTcentreitselfafterSACEPrecommendations.SACEPreview isnotrequired forTDFbasedregimen.HowevereSACEPapprovalshallberequiredford4Tbasedregimenasonlylimitedquantitiesofd4Tshallbeprocuredinfuture

For Second line ART:allpatientsstartingSecondlineARTneedtobe‘transferredout’toCoE/ARTpluscentres.


2.2 ELIGIBILITY AND CRITERIA FOR PROVISION OF SECOND LINE ART

AllpatientswhorequireSecondlineARTshallbereviewedbySACEPasperlaiddownreferralprocedure,irrespectiveofthefactwhethertheystartedtreatmentinprivatesectororNACOcentres

TheSACEPreviewwillbebasedonthereferralfromtheARTcentreprovidingFirstlineARTtothepatientsuspectedoftreatmentfailure.Each COE/ART Plus Centre will have defined ART centres linked to it and patientsfromthesecentres only will be reviewed by a particular COE/ART Plus Centre.

CriteriaforprovisionofSecondlineART:• Referred by the NACO ART centre following the NACO protocol on determining

treatment failure (section 1.6)

• ReviewedbytheSACEPanddeterminedtobemedicallyeligibleaspertheNACOprotocolforSecondlineprovision

• Hasbeenassessedbycounselor/nurse/doctor foradherenceand isprepared forSecond line treatment

• Shouldhavefamilysupport/treatmentsupporter,andlinkedtoNGO/CBO/CSC/ICTCforoutreach/community/homebasedcareservicesandmonitoringofadherence

Furthermore, the patient to be provided Second line ART shall need to sign a consentform for informed consent (ANNEX III)forhomevisits/followedatthecommunitybylinkworker/NGO/positivenetwork/ICTCwhichwillsupporttheadherenceatcommunitylevelforSecondlineprovision.

The SACEP coordinator at COE/Data Manager at ART Plus Centre shall coordinate themeetingoftheSACEPtobeheldattheCOE/ARTPlusCentremeetingroom.TheCOE/ARTPlusCentrewillrequestthepatienttobephysicallypresentforthereviewpanel.TheSMOatARTcentreshouldalsobeinvolvedinthemeeting.

2.3 PROTOCOL FOR SACEP REVIEW

Step1

FollowProtocolA1.1for‘Suspectedtreatmentfailure’andthene-mailthedetails(briefART

history,clinicalstageandserialCD4values,reasonsforreferrals)ofpatienttoCoE/pCoE/

ARTpluscentretogetappointmentdates

Step2

CoE SACEP coordinator/ART plus centre’s datamanagerwill enter patient details intoSACEPregister(1SL+AL)CoESACEPcoordinator/CoEresearchassociate/ARTpluscentre’sdatamanagerwillreviewpatienthistorydetailssentbycentreandgiveappointmentdate(twoalternatives)andtimetothereferringcentrebye-mailforreviewbySACEP

Step3ThereferringARTcentrewillthencommunicatethedate/timetopatientbyphoneand

personalcontactbyORW/DLNvolunteer


Step4

ReferringARTcentrewillsendphotocopiesofpatientrecordstogetherwithReferral/Reply

FormVI and confirm thatCoE SACEP coordinator/ARTplus centre’sdatamanagerhas receivedit.CoESACEPcoordinator/ARTpluscentre’sdatamanagerpreparesweeklySACEPmeetingformats(2SL)

Step5 TheSACEPwillreviewthecasenotesonlyinthepresenceofthepatientandguardian

Step6

TheSACEPwillorderaViralloadtestaccordingtoProtocolA1.2.

BloodsampletobetakentothelinkedViralLoadLabwillbeprocessedaccordingto

Laboratoryguidelinessection

Step7

TheSACEPwillreviewtheViralloadresultsinnextmeetinganddecideonmanagementofthepatientsandwilldocumentoneofthefollowingdecisions:

• ProvideSecondlineART

• Not eligible for Second line ART

• Re-evaluate/others

Step8

OncethedecisionismadebytheSACEPtoprovideSecondlineARTtothepatientreviewed,theclinicalmanagementofthepatientwillbedoneattheCoE/pCoE/ARTpluscentreitself.OnlytheProgramDirectororDeputyProgramDirectorofCoE/pCoEand/orNodalofficerofARTpluscentreprescribeSecondlineART

Step9

TheCoESACEPcoordinator/ARTpluscentre’sdatamanagershallinformthereferringARTcentreforthefollowingactions:

• ‘Transfer-out’thepatientintheM&Eformats,toCoE/pCoE/ARTpluscentre,

• SendthecompletedreplyformtothereferringARTcentre

Step10The patient must undergo 3 counseling sessions (minimum) to ensure treatment preparednessattheCoE/pCoE/ARTpluscentre

Step11 ThefollowupvisitsshallbemonthlyattheCoE/pCoE/ARTpluscentre

Step12

After6-monthsofSecondlineART,thefollowupViralloadtesthastobeperformed.TheresultwillbereviewedbyCoE/pCoE/ARTpluscentre.ThepatientswhohavesuppressedviralloadswithclinicalstabilitymaybetransferredbacktothereferringARTcentre,afterascertainingpatent’swillingness

Step13CoE SACEP coordinator/pCoE/ART plus centre’s datamanager to send SACEPMonthly reporttoNACObye-mailby4thofeverymonth([email protected])underoverallsupervisionofProgramDirector/DeputyProgramDirector&/orNodalofficer

TheCOEProgramDirector/DeputyProgramDirector&/orNodalofficerofARTPlusCentrewillbethephysicianresponsible;backedupbytheCOE/ARTPlusARTcentrestafftoensurehighqualityofcareforthepatienton2ndlineART.Prescriptionofthe2ndlineARTshallbedoneonlybytheProgramDirectororDeputyProgramDirectorofCoE/pCoEand/orNodalofficerofARTpluscentre.

Thepatientwhoisconfirmedtreatmentfailureandistobestarted2ndlinemaybeadmittedattheCOEfortreatmentofanyOIorforreinforcingadherence,ifrequired.TheCOEART


teamshallensurethatthepatienton2ndlineislinkedtoaNGO/CBO/ICTC/CSCforcareandsupportaswellasthepositivenetworkforothersupport.Condomuse,nutritionadviceandpositivepreventionaretobeemphasized.

DetailsinthereportingandrecordingformatsshouldbecompletedbytheCOEstaffsothatgooddocumentationispresent.

2.4 TOR OF ADDITIONAL MANPOWER: SACEP COORDINATOR

Forcarryingouttheseactivities,eachCOEshallbeprovidedwithanadditionalmanpowerinformofaSACEPcoordinator.TheTORsforSACEP Coordinator are:

1. ScreenandreviewallrecordsandcommunicationsofthereferralsmadetotheSACEP

2. MaintainingSACEP-schedulediary,scheduleandcommunicateappointmentdates

ofpatientstothereferringcentres

3. OrganizeSACEPmeetingsandcoordinatewithmembersoftheSACEP

4. EnsurelaboratorytestresultsofpatientsattendingareavailableforSACEPmeetings

5. Coordinatewithpharmacistforpatientdrugtransfers

6. Ensurefollow-upofpatientsattendingSACEP

7. Beresponsibleforpatients’registration,maintainingallformsandregistersrelated

to SACEP

8. PrepareandsendSACEPreportstoSACSandNACO.

9. CoordinatedactivitiesofintheregionlinkedtotheCoE

10. Beresponsible forreceivingandsendingcommunications fromandtothe linked

ART Centres

11. Beresponsibleforalldataentries,maintainingandupdatingallrecords,registers

andfilespertainingtotheCoE

12. AssisttheProgramDirectorandtheDeputyProgramDirectorofCoE inreceiving

andsendingallcommunicationsrelatedtotheCoE

13. Work in the ART centre and perform the duties of DataManager, if and when

required.


14. Responsibleforprocurements,maintainingaccounts,audits,handlingcontingency

pettycashoftheCoE

15. Assistthetrainingandmentoringcoordinatorincommunicationsandmaintaining

records

16. PerformanyotherjobasassignedbytheProgramDirector/DeputyProgramDirector

oftheCoE.

For SACEP meetings at the ART plus centres, the coordinator shall be one of the data managers at the centre and no additional staff shall be provided presently.



Section III: M & E TOOLS

The soft copies of revised M&E tools have been sent to all COE and ART plus centres with instructions on how to use them and only those are to be used. The formats are enclosed at Annex IX.

ThemonitoringplanforSecond-lineARTfocusesontwomainaspectsofNationalART Programme namely – Clinical Monitoring of the Patients and ProgrammePerformance.Thesystemdeveloped;triestobuildontheexistingmonitoringsystemsexisting at ART centres. Refinements are added in current tools to record details of Secondlineandadditionaltoolsaredevelopedforcriticalareasofmonitoring.

Thesetoolswouldallow:

• Clinicianstoeffectivelymonitorthepatienton2ndlineclinically,and

• The ART programme to monitor the progress in implementation, identifyproblems, refine and adapt the implementation strategies; assess theeffectivenessoftheinterventions.

3.1 INSTRUCTIONS FOR MONITORING/RECORDS KEEPING FOR SECOND LINE ART

1. When the patient is referred from any ART centre to COE for evaluation, the patient is NOT ‘Transferred Out’ and would continue to receive the First line drugs from referring ART Centre till recommended otherwise.SACEP/COE(/ARTPlusCentre)willinformthereferringcentreoncedecisionismadeifpatientistobe transferred out or not.

2. Thepatientoncerecommendedfor2ndline;isthentransferredout(T/O)toCoE/ARTpluscentre.ThenormalprocedureofT/Oisfollowed.Therecordsarethustransferredaspertheusualprocedure,ifnotalreadydone.

3. AttheARTcentreofCOE/ARTPluscentres,thecurrentARTenrollmentregisterisusedforrecordingtheclinicaldetailsofthepatientonSecond-linebyfillingtheinformationonswitch

4. InthesameARTenrolmentregistera post fix to the ART registration–S(Secondline)canbeindicatedintheFirstblankcolumnbefore“ARTdateofstart”and“A”foralternativeFirstlineandregistrationnumberaregiveninasequentialorderincontinuationtothepatientsonFirstlineART.


ThesummaryofSecondlineandalternativeFirstlineformatsisasbelow:

Monitoring and Evaluation tools for Second line and Alternative First line ART (Adults and Children)

(To be maintained at CoE/pCoE/ART plus centres)

Tool/Abbreviations M & E Tool- formats/Registers Directions

1

RRFSACEP Referral and Reply form

TobegeneratedatARTCentrewhenreferringthepatient.Thereplyportionto be sent back to referring centre bySACEPafter theevaluationof thepatient.(computerprintedformonly)

1SL*+AL**SACEP register (forallpatientsbeing referred to SACEP )

To bemaintained at CoE/pCoE/ARTplus Centre by SACEP coordinator/datamanager (Hard bound printedregistertobesuppliedbytheSACS).There should be no more than sixrowsperpageinordertoensurethatthere is adequate space forwritingthedetails.

2

2 AL

SACEP Meeting format (alternative First line) Thisformat should be preparedbeforeeverySACEPmeetingforallpatients(childrenandadults)tobereviewedinthatparticularmeeting for consultation forAlternativeFirstlineART

TobepreparedbeforeeverySACEPmeeting;giventoallmembersdur-ingthemeeting;andmaintainedatall CoE/pCoE/ART plus centres (infileringbinderandsoftcopy)

2 SL

SACEP Meeting format (Sec-ond line)

Thisformatshouldbepreparedbefore every SACEP meetingfor all patients (children andadults) to be reviewed inthat particular meeting forsuspectedtreatmentfailure.

TobepreparedbeforeeverySACEPmeeting,giventoallmembersdur-ing themeetingandmaintainedatall CoE/pCoE/ART plus centres (infileringbinderandsoftcopy)

3 3 AL+ SL

Monthly reporting format (Second line and alternative First line)

Combinedmonthly reportingformat for Second line and alternative First line ART foradultsandchildren

To be submitted to NACO byemail by 4th of every month at [email protected].


Tools to be maintained at all CoE/pCoE/ART plus centres (in ring binder file and/or soft copy):

4

4 AL

Line list (alternative First line)

Cumulative list of patientsever initiated on alternativeFirst line ART

To bemaintained at all CoE/pCoE/ARTplusCentresinonecontinuousexcelsheet(softcopyonly)

4 SL

Line list (Second line)

Cumulative list of patientsever initiatedon Second lineART

To bemaintained at all CoE/pCoE/ARTpluscentresinonecontinuousexcel sheet (soft copy only). To bemaintained at referring ART centre also after transfer back of the pa-tientafter6months.

5 5 SL

Centre wise (linked centre information) break up for PL-HIV initiated on Second line ART

LinkedCentrewisecumulativeinformationaboutPLHIV.TobemaintainedatallCoE/pCoE/ARTpluscentresinonecontinuousexcelsheet(softcopyonly)

6 CFConsent form for Second line ART

To be obtained from each patientby SACEP coordinator/data man-agerwhenstartingSecondlineART(computerprintout,signedformtobekeptinringbinderform)

Note: Out of this only SACEP register is to be printed as hard bound register as per printing instructions sent to SACS.RestaretobeusedassoftcopiesandprintoutofsoftcopiestobekeptatCoE/pCoE/ARTpluscentresinseparateringbinderfilesyear-wise.

*SL-SecondlineART**AL-AlternativeFirstlineART

All Second line treatment related formats are enclosed at Annexure IX.

1. SACEP Register (1 SL + AL)wouldbemaintainedbyallCoEandARTPluscentersthatconduct SACEP meetings. The SACEP register is a clinic administration tool whichhelpstotrackpatientsfromreferraltooutcomes,provideinformationforweeklyandmonthlyreportingtoNACO.

• The SACEP coordinator (COE)/datamanager (ART Plus Centre) is responsible formaintainingandupdatingtheregister

• Tofillintheregister,pleasenotethat:

o IthastobeprintedintheformofaregisterandallpatientswhoarereferredtoCoE/ARTpluscentreforSACEP;shouldbeenteredinthisregister


o PatientistobeenteredonlyONCEinSACEP/registerwithdetailsinsamerow.Nomultipleentriesforsamepatientshouldexist(unique)butifthepatientwasnotfoundeligibleforrevieworafterreviewitwasdecidedbytheSACEPthatitisawrongreferralthenanewSACEPnumberwouldbegiventhenexttimethepatientisreferredtoSACEP.

2. SACEP Meeting format (2 SL & 2 AL)recordsthedetailsofeverymeetingandistobemaintainedatCOE/ARTpluscentre

3. Second line monthly ART centre report (3SL + AL) -thisreportistobesentonamonthlybasistoNACObyallCoE’sandARTpluscentres.ThisreportshouldbegeneratedaftercompilationoflinelistsfromallthelinkedARTcentres.

AllCOE/ARTpluscentrewillsentmonthlyreportforalternativeFirstlineandSecondlinecombinedformatsforadultsandchildrentoNACOatSecondline2008@gmail.com latest by 4th of every monthinprescribedformat.

4. Line Lists (4SL/4 AL):AllARTcentresshouldmaintainalistofpatientsonSecondlineandAlternativeFirstlineARTinprescribedformatandsendittotheirlinkedCoE/ARTpluscentre,sothatSecondlinemonthlyARTcentrereportcanbegenerated.

5. Centre wise information (5SL)-linkedcentrewisedetailedinformationonpatientsonSecondlineshouldbeavailablewithallCoEsandARTpluscentres.

Note: Electronic copies (excel) are available for the above formats fromNACO. [email protected]


ARTcenterreferspatientstoSACEP(email).DonotstopFirstlineART

Patientforre-evaluation

SendpatientbacktooriginalARTcenterwithwrittentreatmentplanandSACEPadvice

Refer back to originalARTcenter,withtreatmentplan

“Transfer-Out”

VL>400

VL<400

IfnoOIsendthepatientbacktothereferringARTcentre or else retainthepatientandrepeatviralloadatanother 6months

PatientsentforVLtests

SACEPreviewsVLresults&decidestreatmentplan

2nd line ART initiatedandcontinuedfor 6monthsatCOE/ARTPlusCentre

COE/ARTPlusCentre

(1) Informs ART center to ‘transfer out’ patient

(2)EntryintoCOE/ARTPlusCentrePreART and ART enrollment register as ‘transfer–in’;

(3)Counseltreatmentpreparedness&usecounsellingdiary

SACEP Referral form (ANNEX II) &photocopyofrelevantdocuments(courier)

Replyform, (ANNEX II)

Informsappointmenttime(email)

Labrequestform(ANNEX VII)

Patientnoteligiblefor 2nd line ART

Patienteligiblefor 2nd line ART: Returns for 2nd LineARTinitiation

6month VL and CD4

DATA FLOW

SACEP coordinator:

–Vetsreferrals&ensuredocuments/testsready

–InformARTcenterappointmentdateforSACEP

–EnterspatientdetailsintoSACEPregister (SL-1)

SACEPmeeting:

–WeeklySACEPmeetingsheets(SL-2)

–Updatedetails/decisioninSACEPregister (SL-1)



Section IV: LABORATORY GUIDELINES

4.1 INTRODUCTION:

HIVinfectionhasbecomeapandemicinthelast20years.ThedynamicsoftheHIV/AIDSepidemicinIndiawillhaveamajorimpactontheoveralldiseaseburdenofHIVintheAsia-Pacificregionandtheworld.NationalestimatesindicatethatIndiahas2.1to2.09millionpeoplelivingwithHIVinfection(2011).TheoverallaverageadultprevalenceinIndiais0.27%.

Theviralloadassay(estimationofcopiesofHIV-1ribonucleicacid(RNA)inplasmaofinfectedindividuals)iscriticalinmonitoringpatients’responsetoART(Antiretroviraltherapy)andprogressiontowardsAIDS.Hence,HIV-1viralloadassaywouldbeoneofthekeyparametersforassessmentofpatientswithsuspectedtreatmentfailureonFirstlineART(whomayberequiringSecondlineART).HIV-1viralloadassayresultswillhelptoinitiateSecondlineARTatdesignatedcentersasperNACOguidelines.

Viral loadassaysquantify theamountofHIV-1RNAcirculating in thebloodofaninfected individual. Although total quantification includes cell-free virus, virus ininfectedcells inall compartmentsof thebodyaswellas integratedprovirus, theeasiest measurement of viral load is of cell-free virus in an individual’s plasma.Currentlythereisnoclinicalindicationforviralloadtestingoftissues.HIV-1plasmaviralload(PVL)levelisbeingsuccessfullyusedtopredicttimetoprogressiontoAIDSand to assessefficacyofART.During treatment, thedecayof viral load in tissuestypically corresponds with virologic responses in plasma,making blood plasma ausefulsentinelforvirologicresponseingeneral.

4.2 INTENDED USE OF HIV-1 PVL ASSAY IN NACO’S SECOND LINE ART INITIATIVE:

TheHIV-1PVLassaywillbeperformedinHIVinfectedindividualsthatfailFirstlineARTatNACOdesignatedARTsites.TheresultsofPVLassaywillbeusedtodecidetheinitiation of Second line ART.

ThePVLassaywillbeperformed:

• BeforestartingSecondlineARTtogetthereferencevaluetodecideonfurthercourseofaction.APVLmeasurementwillbeperformedonpatientsreferredbySACEP.ThedecisiononwhethertoswitchARTornotwillbemadebasedontheviralloaddetectedasdetailedbelow:

- PVL < 400copies/ml:Nochangein1st line ART


- PVL 400-5,000 copies /ml:RepeatPVLafter3monthswithstringentmonitoringofpatientforadherencetoFirstlineARTregimen

- PVL >5000 copies/ml:StartpatientonSecondlineART.RepeatPVLafter6monthstoassesssuppressioninviralload

- RepeatPVLassayat12monthsif6monthsPVLismorethan400

• Repeat PVL on the same patient must be done at the same laboratory with the same technique/procedure, using the same platform

* This must be especially noted for laboratories which are initially linked to other laboratories and likely to have their own viral load assay set ups in the near future

If treatment failure is suspected based on immunological (Second confirmation of CD4T cell levels) and/or clinical criteria, theART centremust follow theNACOprotocol formanagementasdetailedinpages19(protocolA1.1).

TheARTcentrewillsuspecttreatmentfailureinpatientswhoareonFirstlineARTforatleast6monthsandhave:

AnewOI(clinicalfailure)

SlowriseofCD4cellsorfailureofCD4cellstoriseafter6-12monthsoftreatment

DeclineinCD4cellsby50%afteraninitialrise,asperNACO/WHOguidelines

PerformCD4cellestimationimmediatelyincasesofsuspectedclinicalfailureandrepeatafter4weeksforconfirmationoffailureasperprotocolA1.1

Simultaneouslyundertakethefollowing:

o EvaluatepatientforARTadherence

o RuleoutpresenceofOIsliketuberculosis,oesophagealcandidiasis,etc.

o Ensurepatienthasbeenoncotrimoxazoleprophylaxis.

o TreatandreviewOIsifpresent.

o TheARTcentretosendtherequestformwithcompletepatientdetailsalongwiththeconfirmedcontactphonenumbertothenodalofficer.

ThenodalofficerreferssuchapatienttoStateAIDSClinicalExpertPanel(SACEP)atCOEsand/orARTplusCentresfordecisiononHIV-1viralloadtesting.

Eligibility

AllHIVpositivepatientsshowingsignsoffailureonFirstlineARTwillbeeligibleforreviewbySACEPfollowingtheproperreferralproceduresfromtheARTcentres:


State-wiselistofCoEsandARTpluscentres

State COE*/ART Plus centre

Tamilnadu GovernmentGeneralChestHospital(GGCH),Tambaram*GovernmentMohan Kumaramangalam Medical College, Salem MaduraiMedicalCollege,MaduraiTirunelveliMedicalCollege,Tirunelveli

Maharashtra GrantGovt.MedicalcollegeandSirJJHospital,Mumbai*Govt.MedicalCollege,AurangabadGovernmentMedicalCollege,Sangli,MaharashtraB.J.MedicalCollege&SassoonHospital,PuneGovt.MedicalCollege,Nagpur

Gujarat B.J.MedicalCollege(BJMC),Ahmadabad*Govt.MedicalCollege,MajuraGate,SuratPanditDindayalUpadhyayHospital,Rajkot

Karnataka BowringandLadyCurzonHospital,Bangalore*KarnatakaInstituteofMedicalSciences,Hubli,KarnatakaVijayanagaraInstituteofMedicalSciences,Bellary,KarnatakaDistrictHospital,Gulbarga,KarnatakaDistrictHospital,Udupi,Karnataka

AndhraPradesh GandhiHospitalandMedicalCollege,Hyderabad*GovernmentGeneralHospital,Vijayawada,AndhraPradeshRajivGandhiInstituteofMedicalSciences,Kadappa,AndhraPradeshKingGeorgeHospital,Visakhapatnam,AndhraPradesh

WestBengal SchoolofTropicalMedicine(STM),Kolkata*

NewDelhi MaulanaAzadMedicalCollege(MAMC),NewDelhi*

Kerala Govt.MedicalCollege,Trichur

Assam MedicalCollegeandHospital,Guwahati

Manipur RegionalInstituteofMedicalSciences(RIMS),Imphal*

Bihar RajendraMemorialResearchInstituteofMedicalSciences,Patna

MadhyaPradesh GandhiMedicalCollege,Bhopal,MadhyaPradesh

Rajesthan SawaiManSinghMedicalCollegeandHospital,Jaipur

UttarPradesh KingGeorgeMedicalCollege,Lucknow

Mizoram CivilHospital,Aizwa

Punjab GovernmentMedicalCollege,Amritsar

Panjab/Haryana PostGraduateInstituteofMedicalEducationandResearch(PGI),Chandigarh*

UttarPradesh InstituteofMedicalSciences(BHU),Varanasi*

Uttaranchal DoonHospital,Dehradun

Jammu&Kashmir GovernmentMedicalCollege,Jammu

Orissa ShriramaChandraBhanjMedicalCollege,Cuttack

13moreARTpluscentreshavebeensanctionedsoastohaveatleastoneARTpluscentreineachstatetoprovideSecondlineART


NOTE:Bloodisnottobedrawnforaviralloadtestwithinfourweeksofanyinfectionorimmunization.

Protocol for the review panel

TheSACEPwillreviewthecasenotesalongwiththepatient.

Thepanelwillthenorderaviralloadtestifrequired.Specimens(wholebloodandDBS)willbecollectedfromthepatientattheCOEonadesignateddayandsenttotheidentifiedviralloadlabasdetailedbelowinthesectiononspecimencollection,storageandtransport.TheSACEPwillmeetonthefollowingdesignatedday(whichifhappenstobeaholidaythenonthenextworkingday)toreviewtheresultsofviralloadassayand,basedontheresultofPVL,decideonfurthermanagementofthecase.

4.3 TECHNIQUES OF HIV – 1 PVL ASSAY:

ViralloadassaysmeasuretheamountofHIV-1RNAinthecollectedplasmaspecimen.HIV-1RNAisresponsibleforHIVreplication.TheamountofHIV-1RNAinplasmacanbemeasuredbythefollowingdifferenttechniquesformeasurementofHIV-1RNA.

Quantitative PCR (polymerase chain reaction) is themost frequently used test.ForPCRtheviralRNAisextracted;anenzymeconvertstheextractedRNAtoDNA(cDNA);thisDNAisthenmultipliedmanyfoldsbythehelpofanenzymepolymerase;theproductisdetectedthroughchangesintheintensity/colorofcertainchemicalmarkers.ThisprocessmakesthedetectionofviralRNAeasier.TheoriginalnumberofRNAcopieswouldbethenquantifiedbasedonthefinalnumbersofcDNAobtained.TestresultsarereportedasHIV-1RNAcopies/ml.

The bDNA (branched DNA) isafairlyfrequentlyusedtest. Itmakesuseofsignalamplification (lightemittingmaterial). Thismaterialbindswith theHIVparticles.Theamountoflightismeasuredandconvertedtoaviralcount.

NASBA (Nucleic Acid Sequence Based Amplification Assay) is an in vitro nucleic acidamplificationtestforquantificationofamplifiedHIV-1RNAwhichismeasuredbymeansofelectrochemiluminescence.

The PCR test results are often different from the bDNA results for the same specimen. Because the tests are different, only one kind of test (PCR or bDNA) should be used to measure a person’s viral load over time.

ViralloadassayresultsarereportedascopiesofHIV-1RNAinonemilliliterofblood.ThebestviralloadassayresultinpatientsonARTis“undetectable”viralload.Thisdoesnotmeanthatthereisnovirusintheblood;itjustmeansthatthelevelisnotenoughtobedetectedthroughthetestused.“Undetectable”level(Noofcopies/mlofplasma)willdependonthesensitivityoftheassaysystemused.


Some relevant terminologies

Sensitivity: Sensitivityisdefinedasthelowestviralloadlevelthatcanbedetectedinthespecimen95percentofthetime.Thestatisticalmethodofassessingsensitivityisgenerallyconsideredtobethestandardtodeterminethequantitative“limitofdetection”(LoD)forquantitativeHIV-1RNAassays

Precision: Theprecisionor reproducibility of an assay is definedby its ability toobtainthesamevaluewhentestedrepeatedly.Inviralloads,precisionismeasuredbytheabilitytodetect“foldchanges”inthelevelsoftheviralloads.

Dynamic Range: Thedynamicrangeofanassayisdefinedasthequantitativerangeoverwhichtheresultsarereliablyreported.

4.4 PLASMA VIRAL LOAD ASSAYS CURRENTLY IN USE IN NACO’S SECOND-LINE ROLL OUT:

4.4.1 AMPLICOR HIV-1 MONITOR TEST, VERSION 1.5

TheAmplicorHIV-1MonitorTest,version1.5(v1.5)isanin vitronucleicacidamplificationtestforthequantificationofHumanImmunodeficiencyVirusType1(HIV-1)RNAinhumanplasma.TheAmplicorHIV-1Test, version1.5usesPCR technology toachievemaximumsensitivity anddynamic range for thequantitativedetectionofHIV-1RNA inEDTAanti-coagulatedplasma.

TheAmplicorHIV-1Monitorversion1.5(v1.5)isprogrammedon,andapprovedforuseonAppliedBiosystemsGene-AmpPCR system9600/9700 thermal cycler. InAmplicorHIV-1monitorthespecimenpreparation ismanual, theamplification isautomatedontheABI9600/9700anddetectionisbymanualELISAorautomatedELISAreader.

The test can quantitateHIV-1 RNAover the range of 50-750,000 copies /ml by using acombination of two specimen preparation procedures, the Standard (dynamic range 400-750,000 copies /ml) and Ultra Sensitive (dynamic range 50-1,00,000 copies/ml)procedures.Testresultslessthan400arebelowthelowerlimitofdetectionoftheStandardtest. If quantitative results are desired for such specimens, original plasma specimensshouldberetestedusingtheUltrasensitivespecimenpreparationprocedure

This test is based on five major processes: specimenpreparation, reverse transcriptionoftargetRNAtogeneratecomplementaryDNA(cDNA);PCRamplificationoftargetcDNAusing HIV-1 specific complementary primers; hybridization of the amplified products tooligonucleotideprobesspecifictothetarget(s);anddetectionoftheprobeboundamplifiedproductsbycolorimetricdetermination.

TheAmplicorHIV-1MonitorTest,v1.5canbeusedwitheitheroftwospecimenpreparationprocedures, the Standard procedure or the Ultra Sensitive procedure. In the Standardspecimen preparation procedure,HIV-1 RNA is isolated directly fromplasmaby lysis ofvirusparticleswithachaotropicagentfollowedbyprecipitationoftheRNAwithalcohol.WiththeUltraSensitivespecimenpreparationprocedure,HIV-1viralparticles inplasma


areconcentratedbyhighspeedcentrifugation,followedbylysisofthevirusparticleswithachaotropicagentandprecipitationoftheHIV-1RNAwithalcohol.Aknownnumberofquantitation standard RNAmolecules are introduced into each specimenwith the lysisreagent. The HIV-1Quantitation Standard is carried through the specimen preparation,reversetranscription,amplificationanddetectionstepsandisusedforthequantitationofHIV-1RNAinthetestspecimen.

4.4.2 COBASAMPLICOR HIV-1 MONITORTM TEST, VERSION 1.5

The CobasAmplicor HIV-1 Monitor Test, version 1.5 (v1.5) is an in vitro nucleic acid amplification test for thequantitationofHuman ImmunodeficiencyVirusType1 (HIV-1)RNAinhumanplasmaontheCobasAmplicorTManalyzer.

InCobasAmplicorthespecimenpreparationismanualandtheamplificationanddetectionstepsareautomated.

The test can quantitate HIV-1 RNA over the range of 50-750,000 copies/mL by using acombinationoftwospecimenpreparationprocedures,theStandard(dynamicrange400-750,000copies/ml)andUltraSensitive(dynamicrange50-100,000copies/ml)procedures.Test results less than400arebelowthe lower limitofdetectionof theStandardtest. Ifquantitativeresultsaredesiredforsuchspecimens,originalplasmaspecimensshouldberetestedusingtheUltrasensitivespecimenpreparationprocedure.

This test is based on five major processes: specimenpreparation; reverse transcriptionoftargetRNAtogeneratecomplementaryDNA(cDNA);PCRamplificationoftargetcDNAusing HIV-1 specific complementary primers; hybridization of the amplified products tooligonucleotideprobesspecifictothetarget(s);anddetectionoftheprobeboundamplifiedproductsbycolorimetricdetermination.

The CobasAmplicor HIV-1Monitor Test, v1.5 can be usedwith either of two specimenpreparationprocedures,theStandardprocedureortheUltraSensitiveprocedure.IntheStandardspecimenpreparationprocedure,HIV-1RNAisisolateddirectlyfromplasmabylysisofvirusparticleswithachaotropicagentfollowedbyprecipitationoftheRNAwithalcohol.WiththeUltraSensitivespecimenpreparationprocedure,HIV-1viralparticlesinplasmaareconcentratedbyhighspeedcentrifugation,followedbylysisofthevirusparticleswithachaotropicagentandprecipitationoftheHIV-1RNAwithalcohol.AknownnumberofquantitationstandardRNAmoleculesareintroducedintoeachspecimenwiththelysisreagent. The HIV-1Quantitation Standard is carried through the specimen preparation,reversetranscription,amplificationanddetectionstepsandisusedforthequantitationofHIV-1RNAinthetestspecimen.

4.4.3 COBAS TAQMAN HIV-1 TEST

TheCOBASTaqManHIV-1Testisanin vitro nucleicacidamplificationtestforthequantitationofHumanImmunodeficiencyVirusType1(HIV-1)RNAinhumanplasmawithEDTA,usingtheHighPureSystemViralNucleicAcidKitformanualspecimenpreparationandtheCOBAS


TaqMananalyzerforautomatedamplificationanddetection.ThetestcanquantitateHIV-1RNAovertherangeof47-10,000,000copies/ml

The COBAS TaqMan HIV-1 Test utilizes real time PCR technology to achieve maximumsensitivity anddynamic range for thequantitativedetectionofHIV-1RNA inEDTAanti-coagulated plasma. The use of dual-labeled fluorescent probes provides for real-timedetection of PCR product accumulation by monitoring of the emission intensity offluorescentreporterdyesreleasedduringtheamplificationprocess.TheCOBASTaqManHIV-1Testaccuratelyprovidesquantitativeresultsoveraverywidedynamicrangesincethemonitoringofamplicon isperformedduringtheexponentialphaseofamplification.ThehighertheHIV-1titerofaspecimen,theearlierthefluorescenceofthereporterdyeoftheHIV-1proberisesabovethebaselinefluorescencelevel.

The COBAS TaqMan HIV-1 Test is based on four processes: Specimen preparationto obtain HIV-1 RNA; Automated reverse transcription of the target RNA to generatecomplementaryDNA(cDNA);SimultaneousPCRamplificationoftargetcDNAusingHIV-1specific complementary primers; and detection of cleaved dual fluorescent dye-labeledoligonucleotidedetectionprobes.

TheCOBASTaqManHIV-1TestprocessesEDTAcontainingplasmaspecimensandisolatesHIV-1 RNA through a generic manual specimen preparation (in case ampliprep is notavailable)basedonnucleicacidbindingtoglassfibers.TheHIV-1virusparticlesarelysedbyincubationatanelevatedtemperaturewithaproteaseandchaotropiclysis/bindingbufferthatreleasesnucleicacidsandprotectsthereleasedHIV-1RNAfromRNAs inplasma.AknownnumberofHIV-1‘QuantitationStandardArmored’RNAmoleculesareintroducedinto each specimenalongwith the lysis reagent. Subsequently, isopropanol is added tothe lysismixturewhich is then centrifuged through a columnwith a glass fiber insert.Duringcentrifugation,theHIV-1RNAandHIV-1QuantitationStandardRNAareboundtothesurfaceoftheglassfiberfilter.Unboundsubstances,suchassalts,proteinsandothercellularimpurities,areremovedbycentrifugation.Theadsorbednucleicacidsarewashedandelutedwithanaqueoussolution.Thedisposablesallowforaparallelprocessingof12specimensormultiplesthereof.Theprocessedspecimen,containingHIV-1RNAandHIV-1QuantitationStandardRNA,isaddedtotheamplification/detectionmixture.TheHIV-1targetRNAandtheHIV-1QuantitationStandardRNAarethenreversetranscribed,amplifiedanddetectedontheCOBASTaqMan-analyzerusingtheamplificationanddetectionreagentsprovidedinthetestkit.

4.5 SPECIMEN COLLECTION, STORAGE, AND TRANSPORTATION:

4.5.1 COLLECTION DAYS AND TIMINGS

Specimencollection is tobedonebetween11.00A.M to1:00PMonSACEPdayasdecidedbythecentre.


Incasethespecimencollectiondayisaholiday,specimencollectionistobepostedonanalternatedaywithpriorarrangementwiththereceivinglaboratory.

Donot collect specimen if nextday to SACEP is aholiday (as specimenshave tobeprocessedforHIV-1PVLbythereceivinglaboratorywithin24hoursofcollection)

Previousarrangementwithtestingcentretobemadeincasethespecimenistobecollectedonadaynotscheduledforthepurpose(Collectionandtransportofspecimen)

4.5.2 SPECIMEN COLLECTION

Standardworkprecautionsaretobefollowedstringently

Page 1 of theVL-1 form (as perAnnex VII) is to be filledmandatorily induplicate/photocopy.(Specimensaccompaniedwithincompleteformswillberejected)

ConfirminformationonVL-1form(patient’sname,registration/accessionnumber,testneeded, date and time of collection, and physician’s/clinic’s name, etc)mandatorilybeforecollectionofspecimens

SterileEDTA(lavendertop)evacuatedbloodcollectiontubesaretobeused.

Thebloodcollectiontubesaretobelabeled (cryolabel)withpatient’sname,registration/accession number, test needed, date and time of collection, and physician’s/clinic’sname. The informationon the form shouldmatch the informationon the specimencollection tube

4ml blood is to be collected and placed in prescribed sterile tubes using EDTA(lavendertop)astheanticoagulant.Do not collect blood in heparin vials. (Thechoiceofanticoagulantusedinbloodcollectiontubescansignificantlyalterviralloadresults,byaffectingeithertheviriondecayrateex vivoorthedetectionbytheassaytypeused.PlasmatreatedwithsodiumheparinisnotappropriateforPCRassaysbecauseheparinisapotentinhibitorofPCR)

In case the linked HIV-1 PVL laboratory is in a different city, Dried Blood Spot (DBS) Preparation and Storage (as per Section 4.13) and then plasma separation (as per below) are to be performed by the ART Centre itself.

In case the linked laboratory is in the same city or same hospital, DBS Preparation and Storage (as per Section 4.13) and then plasma separation (as per below) are to be performed by the PVL laboratory within 6 hours of receipt of specimen.

4.5.3 PACKAGING AND TRANSPORTATION

All specimens will be transported by hand by lab technicians of the centre ofexcellence


Thespecimenistobepackagedcarefullytoprotectfrombreakage,andleakageandinsulatedtoprotectfromextremetemperature.Coolpacksaretobeusedtomaintaintemperatureof2-80C.Ensurewholeblooddoesnotfreezeduringtransportation.

Forpackaging,thetubecontainingthespecimenisplacedinaleakproofcontainer(e.g.asealedplasticbag).

Thecoolpacksaretobeplacedaroundandthepackageistobeplacedinsideapunctureproof containerwith sufficientmaterial to absorb all the contents in case the tubebreaks or leaks.

Capthecontainertightly.

PlacetheVL-1forminanenvelopeandfastensecurelytotheoutsideofthecontainer.

Abiohazardlabelshouldbepastedonthevisibleoutersurfaceofthepackagecontainingthespecimens.

Incasethelaboratoryislocatedinthesamecity:TheLabtechnicianoftheARTcentreshouldtransportthespecimenwiththeVL-1forminduplicateandensuredeliverytothetestinglabofthewholebloodspecimenat2-8oCwithin3hoursofcollection(i.e.by2.00P.M.onMonday/Tuesdayafternoon).

Incasethelaboratoryislocatedinadifferentthecity:TheLabtechnicianoftheARTcentre should transport theplasma specimen (First having prepared, packaged andstoredDBS;andthenseparatedtheplasmaattheARTcentre)withtheVL-1forminduplicateandensuredeliverytothetestinglaboftheplasmaspecimenat2-8oCwithin24hoursaftercollection(i.e.by10AM.onTuesday/Wednesday).

ThetechnicianfromthecentreofexcellencecarryingthespecimensmustparticipatewiththetechniciansatthePVLlaboratoryintheprocessesofestimationofHIV-1PVLinordertolearnthetechniquesinvolved.

The DBS samples will be collected and stored as per section 4.13. It is recommended that the DBS samples be stored at 2-8oC for 20 days and then be couriered to NARI, Pune along with the consent forms. It is important to note that the consent form must be sent to the lab making DBS in case of intercity linkages for sending to NARI, Pune. The details on the envelope may be as follows:

For Second Line roll out

Dr R Paranjape

National AIDS Research Institute (NARI)

73 G Block, MIDC

Bhosari, Pune-411026

Maharashtra, India


4.5.4 RECEIVING SPECIMEN AT THE HIV-1 PVL TESTING LABORATORY

Receivinglabtoidentifythespecimenproperly.Ifthereisdiscrepancyinthetestrequisitionformversusthelabeledtube,DO NOT PROCEED.Takecorrectiveactiontoensurethatthepatient’snameandnumberontherequestformarecorrect.Incaseofanyconfusioncheckbackwiththecollectionsite.

Receiving lab to checkand therebyensureat the timeof specimen receipt that thetemperatureofthespecimenneverexceeded8°Candthewholebloodspecimenwasnotfrozen,duringstorageatthecollectionsiteandtransporttothetestingsite.Leakageisalsocheckedfor.

In case,of anydoubt sendback the specimenandVL-1 formback to theCOE,dulysignedbylabin-charge,withtheCOEtechnician.Anotherspecimenmustbecollectedfor PVL.

ThereceiptofthespecimenstobedulydocumentedonboththecopiesoftheVL-1.

Incasespecimenisrejected,onecopyoftheVL-1formwithsignaturesoflabinchargetobesentbackwiththecenterofexcellencetechnicianbyhandonthesameday.

Receivinglabtorecordthetime/dateofspecimenreceipt.

Do not freeze whole blood. Do not storewhole blood formore than 6 hours aftercollection-evenattemperaturerangeof2-25° C.Plasmaatthereceivinglabhastobeseparatedfromthewholebloodwithin2hoursofspecimenreceipt,within6hoursofspecimencollection(i.e.by4.00P.M.onthesamedayMonday/Tuesday).

4.5.5 PROCESSING OF THE WHOLE BLOOD SPECIMEN IN THE RECEIVING LAB:

AfterpreparationofDBS, theremainingwholebloodspecimen isbecentrifuged forseparationofplasmaasdetailedbelowandprocessedfurtherforestimationofHIV-1PVLaspertheinstructionsofthemanufacturerofthekitbeingused.

o Separationofplasmafromwholeblood:

• Centrifugewholebloodat800-1600xgfor10minutesatroomtemperature.

• Removetheplasmaandrecentrifugeat800xgforanother10minutes.

• Aliquot and store 800-900µl of plasma in a sterile 2 ml polypropylene screw-cappedtube.

• In caseof inadvertentdelay,plasmaspecimen tobeseparatedandstoredat2-8°Covernightandtransportedto thetestingsitenextmorningat2-8°C forperformanceof the teston thesameday (tobeprocessed forPVLwithin24hoursaftercollection).

• Plasmaspecimenistobekeptat2-8°Ctillprocessed.


• Receivinglabmustprocessthespecimenwithin24hoursafterspecimencollection.

• The plasma specimen must be brought to ambient temperature beforeperformingthetestasperthemanufacturer’sprotocol.

o PerformPVLassayaspermanufacturersprotocolontheavailableplatform

4.6 FACTORS TO BE CONSIDERED WHILE INTERPRETING THE VIRAL LOAD RESULTS:

TheHIV-1PVLquantificationassayisinfluencedbymanyfactors.Thustheinterpretationofabsoluteviralconcentrationmeasurementresultsisnotstraightforward.Oneimportantissue to consider iswhethermeasured change in viral loadactually reflects abiologicalevent,orwhether thechange iswithin thevariability limitof theassay.Repeat testsofthe sameblood specimencangive results that varybya factorof3. Thismeans thatameaningfulchangewouldbeadroptoless than 1/3 or an increase to more than 3 times thepreviousviralloadresult.Forexample,achangefrom200,000to600,000iswithinthenormalvariabilityofthetest.Adropfrom50,000to10,000wouldbesignificant.However,themost importantchange inapatientrespondingwell/optimallytoART isreachinganundetectableviralloadlevel.

There is a considerable variation in the results of various types of assays used inquantification of the same specimen but if performed proficiently, a commercial assayshows reproducibilitywithin approximately 0.2-0.5 log10, (varying in different regions oftheassays’dynamicrange).Dailyvariationinviralloadsamongclinicallystablepatientsisminimalatapproximately0.4log10.Thereforeachangeinviralload,greaterthan0.5log10 RNAcopies/ml (approximately3-fold),exceedsassayanddiurnalvariations,andmaybeconsideredtorepresenttruebiologicalevents,whilechangesoflessthan0.5log10 cannot be distinguished whether these are from random variability or a biological event. It isimportanttonotethatinthelowendofthedynamicrange,assayvariabilityhasgreaterimpactoninterpretationofabsoluteviralloadchange.

How are the changes in viral load measured?

Viralloadchangesareoftendescribedas“log”changes.Thisreferstoscientificnotation,whichusespowersof10.Forexample,a2-logdropisadropof102or100times.Adropfrom60,000to600wouldbea2-logdrop.Smallchangesof10,20,30copiesareoftennotconsideredtobeasignificantchangeinviralloadandcanreflectnormalviral“blips,”notachangeintreatmentresponse.

What do the numbers mean?

ItisnotknownhowlongaHIVpositivepatientwouldstayhealthywithanyparticularviralload.AllthatisknownsofaristhatlowerPVLisbetterandseemstomeanalonger,healthierlife.Theviralloadshoulddroptoreachlessthan50copieswithin6monthsofART.EvenwhentheHIV-1viralloadinaHIVpositiveisundetectable,theHIVviruscanbepassedon


toanotherperson,althoughtheriskislower.Thereisno“safe”levelofviralload.

4.7 LIMITATION OF VIRAL LOAD ASSAYS:

RNA assays used tomeasure PVL are perhapsmost heavily relied upon in themedicalmanagementofpeoplediagnosedwithAIDSandinpeoplewhotestpositiveontheHIV-1antibodytests.Asmanyimportantclinicaldecisionsarebasedonthesetests,thehigheststandardsofsensitivityandspecificityarerecommended.Therearehoweversomeconcernswiththeviralloadtestsasgivenbelow:

Intra-assayandbiologicvariabilitymayaffectthefindings.

Theviralloadtestresultscanbeunreliableifthebodyisfightinganinfection,orifthepatienthasjustreceivedanimmunization.Bloodshouldnotbetakenforaviralloadtestwithinfourweeksofanyinfectionorimmunization.Temporaryincreasesin viral load havebeen seen in these instances. Also, the physicianmust reviewthepatient’sadherencetotheARTregimenandshouldpostponetestingifrecentdosesofARThavebeenmissedthatmaycauserapidreplicationofHIV,in vivo.SuchpatientsmayalreadybeexperiencingviralreboundandtheirARTtherapycouldbeincorrectlyjudgedtobefailing.

AdrawbacktoPVLtestingisthehighcostofassaysandrequirementoftechnicalexpertise.

4.8 STANDARDIZATION OF HIV-1 PLASMA VIRAL LOAD REPORTING:

Laboratory reports of viral load assays should be standardized, accurate and adequatefor patient treatment and public health monitoring of the HIV infection and acquiredimmunodeficiencysyndrome(AIDS)epidemic.Toensuretestreportcomparabilityamonglaboratories,standardtestingandreportingmethodsareneeded;moreover,standardizedresults are needed for early detection of treatment failure and early access to patientcare.

Required items to report

ThelaboratoryshouldcompletelyfilloutthereportfoundinAnnexVII(atod),aspertestingplatform.

ItshouldbedulysignedintheVL-1reportingformat(SeeAnnexVII(atod))

ItshouldbesentfromthelabtotheARTcentrebycourierbySaturdaytoreachtheARTcentrelatestbyMonday.Thecourierwillbepaidfromthecontingencygrant.

Acopyofthereportshouldbee-mailedtoNACObySaturdayatdrbbrewari@yahoo.com and [email protected]


4.9 QUALITY ASSURANCE FOR HIV-1 PLASMA VIRAL LOAD TESTING:

Viral load testing is an integral part of themanagement ofHIV disease. It is absolutelyimperative to ensure the accuracy, precision and reproducibility of the test results byadheringtostringentQualityAssuranceandQualityControlmeasuresatalltimes.

QualityAssuranceisdefinedasasetofplannedandsystematicactivitiestoensureadequateconfidencethatrequirementsforqualitywillbemet.

InternalQualityControl refers tothosemeasuresthatmustbetakentoensurethat thetestisworking,thetechnicalaspectsofthetestprocedurehavebeenmet/followedandtheresultsproducedarevalidwithinthelimitationofthetestsystemused.LaboratoriesperformingHIV-1Viralloadquantificationneedtouseexternalqualitycontrolspecimensinadditiontothecontrolscontainedintestkitsforvalidationoftheresult.

Itisrecommendedthatahighpositivecontrol,lowpositivecontrolandanegativecontrolthatcomewiththetestkitsbeincludedwitheachrun.Thecopynumberpermlforeachpositiveresultshouldfallwithintherangeofvalues indicatedinthepackageinsert.Thenegative control should give a less than the lower detection limit result. If controls arenotasexpected, therun isnotvalidand is toberepeated.Thesecontrols shouldmeettheprescribed regulatory requirements for such controls. It is good tohave traceabilitytointernationalreferencestandards.Useofabovetestcontrols,thatareusedtovalidatea test runand toquantitateHIV-IRNA,wouldhowevernotvalidate theanalytic testingprocesswhichmayincludetestingproblemsrelatedtopipetting,inadequateincubationorwashingorvariabilityinkitlotsensitivity.

4.9.1 INVALID TEST RUNS

Wheninvalidpositiveornegativeresultsareobtainedonrunninginternalcontrols,therunisdeclaredinvalidandtheentiretestprocedureforallthespecimenshastoberepeatedinanotherrunbyprocessinganotheraliquotoftheoriginalplasmaspecimens.

Flagsandcommentsmaybegeneratedbytheanalyzerduringtherun.Theoperatormustchecktherunprintout(s)forflagsandcommentstoverifythattherunisvalid.

Withtheexceptionof instrument failuressubsequent to thedenaturationofamplicons,an instrument failure during a test run as indicated by the system errormessages alsoconstitutesaninvalidtestrun.

4.9.2 INTERNAL QUALITY CONTROL (ASSAY CONTROLS-PART OF THE SYSTEM)

Controls are supplied by the manufacturer and are to be processed like patientspecimens.Alowpositive,highpositiveandanegativecontrolaresuppliedwiththekit.Runcontrolstocheckaccuracyandreproducibility.

All quality control failures must be logged and corrective action completed beforespecimenanalysistakesplace.


Allreagentsusedmustbeloggedontologsheetswiththedateopened,expirydateandsignature.Reagentsdiscardedduetocontamination,spillage,etc.mustbeloggedintheappropriatelogsheets.

Reagentsmustbestoredasrecommendedbythemanufactureranddailytemperaturelogsshouldbemaintained.

ResultsshouldbeenteredontoLevy-Jenningsplotstomonitoranytrends,shiftsorbiasin results.

4.9.3 EXTERNAL QUALITY ASSESSMENT

Every testing facility must be able to demonstrate and document its competence inperforming the tests. External quality assessment (EQA) is an evaluation by an outsideagency of the performance of a laboratory on specially supplied small panels of wellcharacterized specimens. The objective is to achieve between-laboratory and between-methodcomparability.

4.9.4 OBJECTIVES OF EQAS

Theprimaryobjectiveistocontinuallyimproveandmaintainthehighstandardofthelaboratory’sperformance,

Tocontinuallyinstituteaformalmonitoringandevaluationprogramme,

Tocontinuallypromotetheconceptofqualityassurance,qualitycontrol,andqualityassessmentinthelaboratory,

Toassessthequalityofserviceoftheparticipatinglaboratory,

Toidentifyproblemsandtakeappropriateinterventionsforcorrectiveactions,

Toencouragetheimplementationofgoodlaboratorypractices,and

Toprovideteachingandtrainingprograms.

Participationinexternalqualityassessment(EQA)isnotasubstitutetodaytodayinternalqualitycontrolpractices.EQAisdesignedtoassesstheintegrityoftheentirelabtestingprocess.Evenwhenallprecautionshavebeentakentoachieveaccuracyandprecisioninthelaboratory,errorsmayarisewhichmaybedetectedbyobjectiveexternalassessment.Theprincipleisthattheassessedmaterial(valuesareknown)issentfromaninternational,national or regional centre to a large number of participating laboratories at regulardesignatedintervals.Theresultsproducedbytheparticipatinglaboratoriesareassessedforaccuracy,precisionandreproducibilityinaconfidentialmannerbythelabconductingEQA.Thelabsproducinginaccurateresultsarerevampedthroughtrainingandtroubleshooting.


TheEQASessentiallycontainsthefollowingcomponents:

Filling up questionnaire to understand the laboratory capabilities and additionalrequirements

TrainingforviralloadestimationprocedureandparticipationinEQAS

ProcessingofthespecimensreceivedunderEQASfollowingtheroutineprocedureofviralloadestimation

SubmissionofreporttotheEQAconductinglaboratory

Doinganalysisofresults,assessmentofperformanceandtroubleshooting

4.9.5 EQA FOR HIV-1 PLASMA VIRAL LOAD TESTING

TheNACOdesignatedlaboratoriesthatwillinitiate/performHIV-1PVLtestingforSecondlinerolloutaretoparticipateinEQAbeingconductedbythecentrelistedbelowforthetime being:

RCPA(RoyalCollegeofPathologistsAustralasia)QualityAssuranceProgramme

RCPA Quality Assurance Programmes Pvt Ltd was established by the Royal College ofPathologistsofAustralasiain1988andisprovidingtheEQAservicestoover40countriesand4,000programsaroundtheworld.RCPAQualityAssuranceProgramPvtLimitedisaNATA (National Associated Testing Authority, Australia) accredited Proficiency Testingprovider forHIV-I RNAViral load and complieswith the requirementsof ILACG13. ThedetailsforEQAaregivenatAnnex-VIII

4.10 OPERATIONAL PLAN FOR HIV-1 VIRAL LOAD TESTING AND EQAS

It is proposed that HIV-1 viral load testing facilities for the National HIV/AIDS care andtreatmentprogrammewouldinitiallybesetupatselectcenters.TheNACOlabsthathavebeenidentifiedtoinitiateandperformHIV-1PVLtestingforspecimensbeingsentbytheNACOidentifiedSecondlinecentresare:

KasturbaHospitalforInfectiousDiseases,Mumbai

TuberculosisResearchCentre(TRC),Chennai

InstituteofHumanBehaviorandAlliedSciences(IHBAS),NewDelhi

NationalInstituteofCholeraandEntericDiseases(NICED),Kolkata

GandhiHospitalandMedicalCollege,Hyderabad


StJohn’sHospital,Bangalore

PostGraduateInstituteofMedicalEducationandResearch(PGIMER),Chandigarh

InstituteofMedicalSciences(BHU),Varanasi

BiramjeeJeejeebhoyMedicalCollege(BJMC),Ahmedabad

RegionalInstituteofMedicalSciences(RIMS),Imphaland

NationalAIDSResearchInstitute(NARI),Pune

NACOhascreatedthefollowinginterimlinkagesuntilallthedesignatedHIV-1PVLtestingcentresbecomeoperational:

The above linked centres, both the COEs and the testing labs, should coordinate theircollectiondaysandtimessothatviral loadspecimensthatarebeingsentfromdifferentcentres to thesame labcanbecoordinated tobeprocessed togetheron thesameday,ensuringtheefficientuseofviralloadreagentsandlaboratorytime.

ItisproposedtoidentifytheeligiblepatientsafteradetailedexaminationbytheSACEP.TheSACEPmeetingwillbeheldonMonday/Tuesday(oranydesignatedday)morningbetween9:00AMto11:00AMdependingontheconvenienceoftheinstitution.EligiblecandidateswillbesubjectedtoHIV-1PVLtestingbeforeSACEPtakesthedecisiontoinitiateSecondline ART.

Bloodspecimen (4ml)willbecollected inanEDTAvacuumevacuated tube immediatelyafterSACEPmeetingandprocessedasgivenbelow:

• IncasethePVLtestinglabisinthesamecityastheCOE:wholebloodspecimenistobetransportedtothePVLtestinglabat2-8oCwithinamaximumof6hoursaftercollection

• IncasethePVLtestinglabisinadifferentcityastheCOE:thelaboratorytechnicianattheCOEwillprepare,package,andstoretheDBS(Section4.13)andseparatetheplasma (asdetailedabove)within2hoursafter specimencollection.Theplasmaspecimen will be stored at 2-8oC until transported by the COE technician. ThespecimenwillbehandcarriedbytheCOEtechnicianfromCOEtothePVLtestinglaboratoryasdetailedabove.TheCOEmustensurethatthelabtechniciancarryingthespecimensmustleavetheCOEthatsameday.

• FrequencyandprocessingofspecimenandtransportdetailswillbeasdetailedinTable1

• OncethespecimenshavebeenreceivedatthePVLtestinglab,estimationofHIV-1PVLmustbedonewithin24hoursafterthespecimenwascollected.

• ThePVLtestinglabmustcourierbackthetestreportstothecorrespondingCOEbytheweekend.Costofthesamewillbemetfromcontingencygrant.

To ensure the quality of the testing on a daily basis and to ensure that all labs meet


internationaltestingstandards,thesecenterswouldparticipateinEQASforHIV-1viralloadtesting.AnattemptisbeingmadetoprovideEQASspecimenstoalltheNACOidentifiedtestinglabsforHIV-1PVLtesting.Alllabsmustparticipateandprovidenecessarycooperationforimplementingthesame.

The details of the EQAS process flow have been annexed at the end of the laboratory guidelines for VL testing.

4.11 PRECAUTIONS AND SPECIFIC INSTRUCTIONS FOR REAGENTS AND EQUIPMENTS:

4.11.1 GENERAL

Viralloadassayisforin vitro measurement of plasma HIV-1 RNA copies and is not for diagnostic use

Treatall specimensaspotentially infectious.AdheretoStandardWorkPrecautionswhenperformingtheassay.

Onlypersonneltrainedinhandlinginfectiousmaterialshouldperformthisprocedure

Screwcappedtubesmustbeusedforprocessingspecimensandcontrolstopreventsplashing and potential cross-contamination of specimens or controls. Do not use snap-cap tubes.Handleallspecimensorcontrols inaccordancewiththeGoodLabPracticesinordertopreventcross-contamination

Donotpipettebymouth.

Donoteat,drinkorsmokeinlaboratoryworkareas.Wearprotectivedisposablegloves,laboratorycoatsandeyeprotectionwhenhandlingspecimensandkitreagents.Washhandsthoroughlyafterhandlingspecimensandkitreagents

Avoidcontactofthesematerialswiththeskin,eyesormucousmembranes.Ifcontactdoesoccur, immediatelywashwith largeamountsofwater.Burnscanoccur if leftuntreated.Ifspillsofthesereagentsoccur,dilutewithwaterbeforewipingdry.

Avoidcontaminatinggloveswhilemanipulatingspecimens

Specimensandcontrolsshouldalwaysbepreparedinthelaminarflow-failuretodosomayresultinspecimencontamination

HandleandmanipulatespecimensinaClassIIBiologicalSafetyCabinet

Thoroughlycleananddisinfectallworksurfaceswithafreshlypreparedsolutionof0.5%sodiumhypochloriteandfollowbywipingdownthesurfacewith70%ethanol.

Anydeviationsfromthespecifiedproceduresandguidelinesmayaffectoptimalassayperformance.


ThistestisforusewithhumanplasmacollectedinEDTAanticoagulantsonly.Heparin has been shown to inhibit PCR and must not be used with this procedure.

4.11.2 REAGENTS STORAGE AND USE

Storereagentsstrictlyaspermanufacturersspecificreagentstoragerecommendations

Visuallyinspecteachreagentbottlebeforeusetoensurethattherearenosignsofleakage and or abnormal colour.

Donotuseakitafterexpirydate.DONOTinterchange,mixorcombinereagentsfromkitswithdifferentmasterlotnumbers.Ensurethatallreagentsusedareofthesame master lot of reagents.

Addallreagentsusingapipettecapableofaccuratelydeliveringspecifiedvolumes.

Regularlycalibratepipettesforaccuratedeliveryandmaintainlogs

Avoidmicrobialandribonucleasecontaminationofreagentswhenremovingaliquotsfromreagentbottles.TheuseofsteriledisposablepipettesandRNase-freepipettetipsisrecommended.

Donotfreezereagentsorcontrols

Donotpoolreagentsfromdifferentlotsorfromdifferentbottlesofthesamelot.

4.11.3 EQUIPMENT

Performmanufacturerrecommendedmaintenanceandcalibrationofallequipment,includingpipettestoensureproperfunctioning.

4.11.4 WORK AREAS

Tominimizethepossibilityoflabareasbecomingcontaminatedwiththeamplicon,thelabareashouldbeseparatedintoseveraldistinctareasorganizedaroundthepre-amplification(separatereagentandspecimenpreparationareas)andpost-amplification(AmplificationandDetection)areas.Personnel shoulduseproperanti-contamination safeguardswhenmovingbetweenareas.

Workflowinthelaboratorymustproceedinauni-directionalmanner,beginninginthePre-AmplificationAreaandmovingtothePost-Amplification(AmplificationandDetection) Area.

Pipettes and other supplies should be dedicated to a specific area. Specimens,equipmentandreagentsshouldnotbereturnedtotheareawhereapreviousstepwasbeingperformedandshouldnotbeusedforotheractivitiesormovedbetweenareas


Pre-amplification activitiesmust beginwith reagent preparation and proceed tospecimenpreparation.

Suppliesandequipmentmustbededicatedtoeachpre-amplificationactivityandnotusedforotheractivitiesormovedbetweenareas.EquipmentandsuppliesusedforreagentpreparationmustnotbeusedforspecimenpreparationactivitiesorforpipettingorprocessingamplifiedDNAorothersourcesoftargetDNA

Glovesmustbewornseparatelyineachareaandmustbechangedbeforeleavingthatarea.

The pre-amplification area should have a template free area for preparation ofreagentsandanampliconfreeareaforspecimenandcontrolpreparation

Post-amplificationsuppliesandequipmentmustremain inthePost-AmplificationArea at all times

The post-amplification area should have analyzer(s) and Data station(s) withadditionalareaforpreparingWorkingAmplificationandDetectionreagents.

4.12 TROUBLE SHOOTING:

Whileperformingtheviralloadsinthelab,therewillbeoccasionswhenthingsmaygowrong.Theproblemscouldoccurbecauseofmechanical, chemicalorhumanerror. Staff should be trained to recognizewhen there is a problemand how tocorrectthemsothatthefinalpatientresultssentoutarenotaffected.Pleasefollowthemanufacturer’sinstructionsfortroubleshooting

Note: Adhere to standard work precautions and PEP as per NACO HIV testing. Keep eye splashers, body showers and supply of running tap water within vicinity of the working lab

4.13 DBS COLLECTION FOR ALL PATIENTS UNDERGOING VIRAL LOAD TESTING

The national programme will collect DBS samples from all patients who are sent for Viral load. The consent form is as annex IV (integrated consent for 2nd line ART as well as for collection of blood for storage)

The purpose of this collection and storage of blood on Dried Blood Spots (DBS) frompatientsundergoingevaluation for Second-lineART in India, is to subsequently conductHIVgenotypicresistancetestingonthesespecimenstoevaluatethepatternsofHIVdrugresistancethathavedevelopedamongpatientswhohavedevelopedtreatmentfailuretothestandardFirst-lineARTregimen.Clinicaland laboratorydatawillbeabstracted frompatientrecordstofurtheranalyzeandcorrelateHIVDRfindingswithvirologic,immunologic,andclinicaloutcomesofpatientsreceivingSecond-linetreatment.Overall,thefindingsoftheseanalysescanbeusedtoguidetheexpansionofARTservices,andspecificallySecond-lineARTservices,inIndia.


The objective of the analysis will be:

1. To determine the patterns of HIV-DR that are present among patients who havedevelopedtreatmentfailuretothestandardFirst-lineregimen,

2. TodetermineifHIV-DRpatternsattherapyswitchhaveanimpactonvirologicsuppressionat6monthsand/or12monthsamongpatientswhoreceiveSecond-linetherapy,and

3. Toevaluatetheclinical,immunologic,andsurvivaloutcomesofpatientswhodevelopedfailuretoFirst-lineARTat12and24months.ThisanalysiscanbestratifiedbyHIVRNAatthetimeofinitialSecond-lineevaluation(<400copies/mL,401-5,000copies/mL,>5,000copies/mL)

4.13.1 SPECIMEN COLLECTION, PROCESSING, AND STORAGE:

BloodisroutinelycollectedfrompatientsatthetimeofevaluationforSecond-lineARTattheSACEP (COE) forHIVRNA,chemistrypanel, liver function tests,andcompletebloodcount.Atthistime,adriedbloodspecimen(DBS)willalsobecollected.

Specimen collection:

DBS should only be made from patient’s blood tubes that have been specificallylabelled ormarked as eligible. Before the DBS ismade, the DBS-ID and ART-ID for theparticipant should be written on the filter paper card. Anti-coagulated blood shouldbe spotted onto filter paper within 24 hours of collection. The filter paper shouldbe handled only at the edge; the areas that will be used to collect specimens shouldnot be touched. A filter should only be spotted with the blood of a single patient. Forrecentlycollected,freshwholeblood,invertthebloodcollectiontube2-3timestomixthewholeblood.Carefullyopenthebloodcollectiontube.Useapipette(withdisposabletip)toaspirate100µlofwholebloodandapplyittothecentreofonepre-printedcircletofullysaturatethecircle.Repeatthisproceduretofilleachcircleonthecardwithblood.Foreachspecimenatleastfoursaturatedcirclesshouldbeobtained.Openingofthetubesandpipettingshouldbeperformedfollowingstandardlaboratorybiosafetyprecautions.

Specimen drying:

Avoidtouchingthepartofthecardwiththebloodspot..Dryallspecimencardsatleast4 hours at ambient temperature in a suspended horizontal position. Depending on theclimateitmightbenecessarytoallowspotstodryovernight.Donotuseoventofastenthedryingtimeofthecards.Whendry, thespotsshouldbeauniformdarkbrown.Theappearanceshouldbesimilartothatofadriedbloodstainandnoareasofredcolorationshouldbeseen.


Specimen packaging:

MakesuretheDBSorDPSarecompletelydrybeforepacking.PackagingofeachDBScardintoaseparategas-impermeablezip-lockbagwith2-3desiccantpacks(toremoveanyresidualmoisture fromthecards)perbagandahumidity indicatorcard (to indicate therelativehumidity inside thebag) is recommended.Whenpacking,make sure that thehumidityindicatorcardsarefacedoutside.Placethefrontofthehumidityindicatorcardfacingoutsidesothatthemarkingsareclearlyvisible.Pressthebagwithbothhandstosqueezeouttheairfromthebagandthensealit.Place5-10oftheabovesmallbagsintoalargeplasticbag.Inthelargeplasticbag,alsoplaceaprintedmanifestwithspecimeninformation.Plasticorfoilbagsused for storage mustbegasimpermeabletokeepthecontentsofthebaghumidity-free.Bagsavailablefromgrocerystoresorotheroutletsthatdonotsellscientificsuppliesareinadequate.

Humidityindicatorcardsanddesiccantpackshaveacolorindicatorwhichchangesfrombluetopinkashumidityincreases.Allhumidityindicatoranddesiccantsshouldbereplacedwithfreshmaterialbeforetheyhaveallchangedtoapinkcolour.ToensureproperpackagingoftheDBScards,thehumidityindicatorcardshouldbeexaminedonceaweekifthesampleiskeptatroomtemperature.Beforeplacingdesiccantpacksintoazip-lockbagwithDBS,makesuredesiccantpackshaveremaineddryduringstorage(indicatorcardshouldshowbluecolor).Whenan indicator isbeginningtochange, it is timetochangethehumidityindicatoranddesiccantpacks.DesiccantpackscanbecomemoistafterusewithDBS,butalsoafterstorageinahumidenvironment.Storedesiccantpackswithhumidityindicatorcardstoevaluatewhethertheirmoisturelevelhasbecometoohigh.Humiditycardsanddesiccantpackscanbere-used.Moisthumidityindicatorcardsanddesiccantpacksshouldbedriedina65°Covenovernightuntilthecolourindicatorreturnstoblue.Removefromtheovenandstoreinasealedbagwithahumidityindicatorcarduntilreuseoruntiltheyonceagainneedtobedriedintheoven.

Specimen storage:

Forshort-termstorage(preferablytwoweeksmaximum,butnomorethan30days)atthecollectingsites,DBScanbekeptinthegasimpermeablezip-lockbagswithdesiccantsandstoredatroomtemperature.DBSheldatroomtemperatureshouldbestoredinaboxorcontainersothatdirectlightwillnotdamagethem.DBSshouldbeexaminedfrequently(e.g.,weekly)toevaluatewhetherthe30%circleinthehumidityindicatorcardhaschangedtoapinkcolor;whenitdoes,thedesiccantsmustbechangedimmediately.

DBScanbekeptatroomtemperatureorat4°Conly forshorttermstorage(<30days).DBSshouldnotbefrozenatthecollectionsiteunlessdefinitearrangementscanbeguaranteedtomaintaintheminafrozenstateuntiltheyreachthegenotypinglaboratory.Insettingswhereconstantrefrigerationmaynotbepossiblebecauseoffrequentelectricityoutages,orwherehighhumidityislikelywithintheavailablerefrigerator/freezer,itispreferabletoholdtheDBSatroomtemperature.Ifpossible,DBSshouldnotremainatacollectingsitewithlimitedstorageconditionsformorethan7daysbeforebeingtransportedtoalaboratorywithaconstantelectricitysupplyandarefrigeratororfreezerinwhichthehumidityhas


beenevaluatedandconfirmedassuitableforlong-termstorageofDBS.

For long termstorage (>30days),DBS shouldbe transported toa central facilitywherethereisaconstantelectricitysupplyinafreezerat20°C or belowthathasbeenevaluatedandconfirmedassuitableforlongtermstorageofDBS.Iffrozen,DBSshouldonlybetakenoutofcoldstoragewhentheyarebeingtransportedtoareferencelaboratoryortested.

Specimen Transport

DBS should be transported to the regional or national genotyping laboratory using thequickestandreliablearrangements.Unlesshumidityattheblooddrawsiteissubstantiallyhigherthanintheprocessinglaboratory,andprovidedsuitablestorageboxesareavailableatthesitetokeepDBSfromlightandcontamination,nospecialarrangementsneedbemadetotransportDBSmoreoftenthanweekly.

Forspecimensthathavebeenstoredatroomtemperature:Thedesiccantsinthespecimensbags shouldbe changedbefore transport forDBS specimens thathavebeen stored forlongerthan7daysatthecollectionsite.Thisshouldbedoneeveniftheindicatorremainsblue.Resealthebagandtransportspecimensbythefastestmeansusingcourierserviceorthroughthepostalsystem(preferablywithexpeditedserviceandaguaranteeddelivery)at roomtemperature.

For specimens that have been stored at 4oC: Remove the bagged specimens from therefrigeratorandallowthemtoreachroomtemperaturebeforeopeningthebag.Oncethesealedbaghasequilibrated,openitandremovetheolddesiccants.Addfreshdesiccantsand reseal the bag. Transport the bag by the fastestmeans. If a cooler is available fortransportthiswillprotectspecimensfromshortperiodsofhightemperature.

Forspecimenshavebeenfrozenat-20oCor-70oC:Thesespecimensshouldbetransportedondryiceorliquidnitrogen.ThawingoffrozenDBSspecimensshouldbeavoidedifpossible.Acoolerisnotsufficienttomaintaintheminafrozenstate.

AllDBS specimens shouldbe logged into the survey system (whether it is anotebookoracomputersoftwarepackage).Thelogshouldincludenotesonspecimenqualityandpackaging.

ThelogbookshouldincludearecordofeligiblespecimensforwhichthereisnoDBSmaterialavailabletobesenttothegenotyping laboratory,andthereason.Anacknowledgementor notification system should be set up involving the survey coordinator, the transportsystem,andthereceivinggenotypinglaboratory,toensureallDBSaredeliveredpromptlytogenotypinglabandarriveingoodcondition.Eitheremailorfaxnotificationusingtheshippingmanifestsmaybeusedforthispurpose.DBSshouldbere-examinedforpackagingandspecimenqualityonarrivalinthegenotypinglaboratoryandrecordedinthegenotypinglaboratory.

Every ART centre shall be linked to a VL lab for which instructions will be given by NACO to send the DBS filter paper to the corresponding HIV drug resistance genotyping national reference labs.


ANNEXURE

ANNEX I:

SEVERITY GRADING OF SELECTED CLINICAL AND LABORATORY TOXICITIES

(source:DivisionofAIDS,NationalInstituteofAllergyandInfectiousDiseases,USA–Modifies,)

ForabnormalitiesNOTfoundelsewhereinthetoxicitytableusethescaletoestimategradesoftoxicity.

GRADE 1Transientormilddiscomfort;nolimitationofactivity;nomedicalintervention/therapyrequired.

GRADE 2Mildtomoderatelimitationofactivity;someassistancemaybeneeded;noorminimalmedicalintervention/therapyrequired.

GRADE 3Markedlimitationofactivity;someassistanceusuallyrequired;medicalintervention/therapyrequired;hospitalizationpossible.

GRADE 4Extremelimitationofactivity;significantassistancerequired;significantmedicalintervention/therapyrequired;hospitalizationorhospicecare.

HAEMATOLOGY GRADE 1 GRADE 2 GRADE 3 GRADE 4

Haemoglobin 8.0–9.4g/dlOR80-94g/lOR4.93–5.83mmol/l

7.0–7.9g/dlOR70-79g/lOR4.31–4.92mmol/l

6.5–6.9g/dlOR65-69g/lOR4.03–4.30mmol/l

<6.5g/dlOR<65g/lOR<4.03mmol/l

Absoluteneutrophilcount

1000–1500/mm³OR1.0–1.5/G/1*

750–999/mm³OR0.75–.99/G/1*

500–749/mm³OR0.5–0.749/G/1*

<500/mm³OR<0.5/G/1*

Platelets 75000–99000/mm³OR75–99/G/1*

50000–74999/mm³OR50–74.9/G/1*

20000–49999/mm³OR20–49.9/G/1*

<20000/mm³OR<20/G/1*


CHEMISTRIES GRADE 1 GRADE 2 GRADE 3 GRADE 4

SODIUM

Hyponatraemia 130–135meq/IOR130–135mmol/l

123–129meq/IOR123–129mmol/l


<166meq/IOR<116mmol/l

Hypernatraemia 146–150meq/IOR146–150mmol/l



>165meq/IOR>165 mmol/l

POTASSIUM

Hyperkalaemia 5.6–6.0meq/IOR5.6–6.0mmol/l

6.1–6.5meq/IOR6.1–6.5mmol/l


>7.0meq/IOR>7.0 mmol/l

Hypernatraemia 3.0–3.4meq/IOR3.0–3.4mmol/l



<2.0meq/IOR<2.0mmol/l

BILIRUBIN

Hyperbilirubin-armia >1.0–1.5xULN >1.5–2.5xULN >2.5–5.0xULN >5.0 x ULN

GLUCOSE

Hypoglycaemia 55–64mg/dlOR3.01–3.55mmol/l

40–54mg/dlOR2.19–3.00mmol/l

30–39mg/dlOR1.67–2.18mmol/l

<30mg/dlOR<1.67mmol/l

Hyperglycaemia(nonfastingandnopriordiabetes)

116–160mg/dlOR6.44–8.90mmol/l

161–250mg/dlOR8.91–13.88mmol/l

251–500mg/dlOR13.89–27.76mmol/l


Triglycerides 200–399mg/dlOR2.25–4.51mmol/l

400–750mg/dlOR4.52–8.47mmol/l

751–1200mg/dlOR8.48–13.55 mmol/l


creatinine >1.0–1.5xULN >1.5–3.0xULN >3.0–6.0xULN >6.0 x ULN

TRANSAMINASES

AST(SGOT) 1.25–2.5xULN >2.5–5.0xULN >5.0–10.0xULN

>10.0 x ULN

ALT(SGPT) 1.25–2.5xULN >2.5–5.0xULN >5.0–10.0xULN

>10.0 x ULN

GGT 1.25–2.5xULN >2.5–5.0xULN >5.0–10.0xULN

>10.0 x ULN

AlkalinePhosphatase 1.25–2.5xULN >2.5–5.0xULN >5.0–10.0xULN

>10.0 x ULN

Pancreaticenzymes

Amylase >1.0–1.5xULN >1.5–2.0xULN >2.0–5.0xULN >5.0 x ULN

Pancreaticamylase >1.0–1.5xULN >1.5–2.0xULN >2.0–5.0xULN >5.0 x ULN


CHEMISTRIES GRADE 1 GRADE 2 GRADE 3 GRADE 4

TRANSAMINASES

Lipase >1.0–1.5xULN >1.5–2.0xULN >2.0–5.0xULN >5.0 x ULN

Lactate <2.0xULNwith-out acidosis

>2.0xULNwith-out acidosis

Increased lactatewithpH<7.3withoutlife-threateningconsequences

Increased lactate withpH<7.3withlife-threat-ening conse-quences

GASTRO- INTESTINAL GRADE 1 GRADE 2 GRADE 3 GRADE 4

Nausea MildORtransient;reasonable intake maintained

Moderate discomfortORintake decreased for<3days

Severediscom-fortORminimalintake for >3 days

Hospitalizationrequired

Vomiting MildORtran-sient;2–3episodesperdayORmildvomitinglasting<1week

ModerateORpersistent;4–5episodesperdayORvomitinglast-ing >1week

Severevomit-ing of all foods/fluidsin24hoursORorthostatichypotensionORintravenousRxrequired

HypotensiveshockORhos-pitalizationforintravenousRxrequired

Diarrhoea MildORtran-sient;3-4loosestoolsperdayORmilddiarrhealasting<1week

ModerateORpersistent;5-7loosestoolsperdayORdiarrhealasting>1week

BloodydiarrheaORorthostatichypotensionOR>7 loose stools/dayORintrave-nousRxrequired

HypotensiveshocksORhospitalizationrequired

RESPIRATORY GRADE 1 GRADE 2 GRADE 3 GRADE 4

Dyspnoea Dyspnoeaonexertion

Dyspnoeawithnormalactivity

Dyspnoeaatrest Dyspnoearequir-ingO²therapy

URINALYSIS GRADE 1 GRADE 2 GRADE 3 GRADE 4

Proteinuria

Spoturine 1+ 2+ or 3+ 4+ Nephroticsyn-drome

24–hoursurine 200 mg to 1 gloss/dayOR<0.3%OR<3g/l

1 g to 2 g loss/dayOR0.3%to1.0%OR3gto10 g/l

2 g to 3.5 g loss/dayOR>1.0%OR>10 g/l

Nephroticsyn-dromeOR>3.5gloss/day

Grosshaematuria Microscopiconly Gross,noclots Grossplusclots Obstructive


MISCELLANEOUS GRADE 1 GRADE 2 GRADE 3 GRADE 4

Fever(oral,>12hours

37.7–38.5°COR100.0–101.5°F

38.6–39.5°COR101.6–102.9°F

39.6–40.5°COR103–105°F

>40.5°COR>105°Ffor>continu-oushours

Headache Mild;noRxre-quired

ModerateORnon-narcoticanalgesia Rx

ServereORre-spondstoinitialnarcoticRx

Intracable

Rashhypersesnitiv-ity

Erythema,prui-tus

Diffusemaculo-papularrashORdrydesquama-tion

VasiculationORmoistdesquama-tionORulcer-ation

ANYONEOF:muscous mem-braneinvolve-ment,suspectedStevens-Johnson(TEN),erythemamultiforme,ex-foliativederma-tistis

Fatigue Normalactivityreduceby<25%

Normalactivityreduceby<25–50%

Normalactivityreduceby>50%:cannotwork

Unable to care for self


ANNEX II:Request/Reply form to SACEP for review of patients suspected of treatment failure (to

be sent with patient records)

RRF: Request form to SACEP at COE /pCoE/ART plus Centre for Review

Dear Dr …………………………………………. Referral date……………………….

Centre of Excellence /ART plus Centre ………………………………

I would like to refer this patient for review by the SACEP for

Alternative First-line ARV ART drugs

Suspect Treatment Failure

Others (specify)…………………………………………….

Name……………………………………………………………......................................... Age-………… Sex…………................……..………

Name of the Care giver ..............................................................................................

Address & Phone no. …………………………………………………………………………………..…………..

………………………………………………………………………………………………………………………………...

........................…........................................................................................................

ART centre name & phone no. ….................................................................................

Contact person at ART centre&mobile no. …………………………………………………………………………........................................................Name & Contact no. of Linked NGO/CCC /DLN:The following are attached with this request form:

• PhotocopyofthePatienttreatmentrecord(WhiteCard)• PhotocopyofalllabtestsincludingCD4• Photocopyofallotherrelevantmaterial• Photodocumentationoftoxicity(Ifavailable)• Addressproofwithphoto

The following sections summarize the patient antiretroviral therapy history:

A: Summary of the case history of the patient (pre-ART; ART; suspected treatment failure/suspected ARV toxicity)…………………………………………………………………………………….............................................B. Summary of adherence history and other psycho-social issues…………………………………………………………………………………….............................................

C. Summary of relevant laboratory tests including CD4 (of last 1 month) /viral load (if available)

…………………………………………………………………………………................................................

Name and Signature of Nodal Officer of referring

ART centre with contact number & email


Reply from SACEP at CoE/pCoE/ART plus Centre to Referring ART centre (After review)

Dear Dr ……………………………………………………… Date………………………...…….

ART centre…………………………………………………..

Patientname…………………………………………………..............…Gender/Age………….............….....…

Address……………………………………………………..................... SACEP registration no. …………………………………

Referred for………………………………………………..................…on Date……………………………................…………….

Findings/investigationresults:…………………………………………………………………….........................………………....................

……………………………………………………………………………………………………………….…………………….……

……………………………………………………………………………………………………………………………………………

Treatment/follow-upPlan:……………………………………………………………………………….…………………

……………………………………………………………………………………………………………………………………………

NameandSignatureofNodalOfficer

COE/ARTpluswithcontactnumber&e-mail


ANNEX III:

CF Consent form for patients starting Second line ART – at COE

Consent form for patients starting Second line ART

I, (name)…………………………………, (address) …………………………………................................. CONSENTtoshareall informationpertaining tomyhealthandHIV/AIDSstatuswith theserviceproviderswhowillbepartofthemanagementofmycondition.

And

I AGREEtoreceivetheSecondlineantiretroviraltherapy.

Ifullyunderstandtheinformationthathasbeenprovidedbythehealthcarestaffinthefollowing:

• ThatSecondlineARTisnotanemergencyandthuswillbestartedasperthedeci-sionofthedoctor.IshallattendtheARTcentreasperappointmentfortimelyinitia-tionofARTandregularfollowup

• ThatreceivingSecondlineARTinvolvessharedconfidentialitywithotherserviceproviderssuchasCBO/NGO/CCC/positivenetworkwhomayconductoutreachandhome-basedcareactivitiesathome

• ThatSecondlineARTrequires100%adherencetodrugsandIshallabidebythesame.

• ThatthereisnothirdlineARTavailableintheprogramme

• ThatIunderstandthesideeffectsofSecondlineART

• ThatIshallnotstopthedrugsonmyownandwillreturntothecentreifthereisanyproblem

• ThatthenationalprogrammeshallcollectandstoremybloodtofindoutiftheARTmedicinesareworkingagainsttheHIVatalaterdate(Drugresistancetestingetc).Thiswillnotaffectmycurrenttreatment.Thiswillhelpthedoctorstoimprovethecareandtreatmentofallpatientsundergoingtreatmentatthiscentre,andpossi-blyatothercentresinthecountry.

…………………. …………………

SignatureofwitnessSignatureofpatientwithdate

(Doctor/nurse/counselor)

(This should be translated in local language &/or explained for patient understanding before taking patients signature)


Drug information on Second line ARVs

LPV/r drug-drug interactions

Class Proteaseinhibitor(PI)

NACO Formulation Heat stable tablet: 200 mg LPV + 50 mg RTV

Contraindication LPV/riscontraindicatedinpatientswithknownhypersensitivitytoLPV or RTV

Safety in pregnancy NodataonLPV/rinpregnantwomen.LPV/rshouldnotbeusedduringpregnancyandbreastfeeding.

Precautions Hepaticimpairment–avoidifsevererenalimpairment,pregnancy;breastfeeding.

Food Shouldbetakenwithfood

Interactions IfddIorantacidsareadministered,theyshouldbetakenatleast1hourapart

LPVshouldnotbetakenwiththesedrugs:amiodarone,astemizole,cisapride,ergotamineandsimilaralkaloids,flecanide,garlicsupplements,lovastatin,midazolam,pimozide,propadenone,rifamipicin,simvastatin,StJohn’swort,terfenadineandtriazolam

RifamipicinshouldnotbeusedincombinationwithLPV/rbecauseco-administrationmaycauselargedecreasesinLPVconcentrations.

LPVlevelsareincreasedbydelavirdineandRitonavir(RTV)

LPVlevelsaredecreasedbyamprenavir,carbamazepine,dexamethasone,Efavirenz,ketoconazole,nevirapine,Phenobarbital,StJohn’swort,phenytoin,rifamipicinandTDF.

LPVincreasesthelevelsofamiodaron,amprenavir,atorvastatin,bepridil,calciumchannelblockers,clarithromycin,ketoconazole,indinavir,itraconazole,lidocaine(systemic),quinidine,rifabutin,saquinavir,sildenafilandTDF.

LPVdecreasesthelevelsofamprenavir,atovaquoneandmethadone.

LPVhaspotentialinteractionswithanticonvulsants,statins,oralcontraceptives,tricyclicantidepressants,oralanticoagulantsandimmunosuppressants.

ANNEX IV:


Adverse effects GI-related:diarrhoea,nausea,vomiting,colitis,abdominaldiscom-fort,asthenia,headache,insomnia,rash.

Less frequently: drug mouth, hepatic dysfunction, pancreatitis,dyspepsia, dysphagia, oesophagitis, influenza-like syndrome,appetite changes, hypertension, palpitations, thrombophlebitis,vascultitis,chestpain,dyspnoea,agitation,anxiety,ataxia,hypertonia,confusion,depression,dizziness,dyskinesia,parasthesia,peripheralneuritis, somnolence; Cushing syndrome, hypothyroidism, sexualdysfunction, anaemia, leucopenia, dehydration, oedema, lacticacidosis; arthralgia, myalgia, abnormal vision, otitismedia, tastedisturbances, tinnitus, acne, alopecia, drug skin, pruritis, skindiscoloration,naildisorders,sweating;Lipodystrophyandmetaboliceffects, raisedbilirubinand loweredsodium,lowplateletand lowneutrophilcountsalsoreportedinchildren.

Storage Roomtemperature(below30degrees)

Lamivudine (3TC)

Class Nucleosidereversetranscriptaseinhibitor(NsRTI)

NACO Formulation CombinedasfixeddosecombinationasTDF/3TCatdoseof300mgonceaday

Contraindication Knownsensitivityto3TC

Safety in pregnancy Limiteddataavailableonsafetyof3TCinhumanpregnancy

Precautions Renalimpairment

Hepaticimpairment:potentiallylife-threateninglacticacidosisandseverehepatomegalyreported,cautioninliverdisease.RecurrenthepatitismayoccurinpatientswithchronichepatitisBinfectionondiscontinuationof3TC

Food Canbetakenwithorwithoutfood

Interactions Rare

Adverse effects Nausea,vomiting,diarrhoea,abdominalpain,cough,headache,fatigue,insomnia,malaise,fever,rash,alopecia,muscledisorders,nasalsymptoms;peripheralneuropathyreported;rarelypancrea-titis;neutropenia,anaemia,thrombocytopenia;lacticacidosis/hepaticsteatosis;raisedliverenzymesandserumamylase

Storage Roomtemperature(15-30degreesC)


ATV/r drug-drug interactions

Class Proteaseinhibitor(PI)

NACO Formulation Atazanavir300mgandritonavir100mg

Contraindication ATV/riscontraindicatedinpatientswithknownhypersensitivityto ATV or RTV

Safety in pregnancy NodataonATV/rinpregnantwomen.However,itsefficacyinpregnancyislessthanLPV/r.

Precautions Hepaticimpairment–avoidifsevererenalimpairment.

Food Shouldbetakenwithfood

Interactions In case of regimen IV/IVa1. H2receptorantagonistdoseshouldnotexceedadoseequiva-

lenttoFamotidine40mgBIDinART-naïvepatientsor20mgBIDinART-experiencedpatients.

2. GiveATV300mg+RTV100mgsimultaneouslywithand/or>10hoursaftertheH2receptorantagonist.

Example: If a PLHIV on Zidovudine + Lamivudine + Atazanavir/Rito-navir (Regimen IV) requires to be treated with Famotidine 20 mg BID or Ranitidine 150 mg BID, S/he should be instructed to take Tab. Famotidine/Ranitidine with Zidovudine + Lamivudine at 8.00 AM and in evening give ZL and ATV/r at 8 p.m. and ensure that there is a gap of at least 2 hours before or 1 hour after Famotidine/Ranitidine evening dose.In case of Second line Regimen V (Tenofovir + Lamivudine + Ata-zanavir/Ritonavir):

1. PPIs shouldnotexceedthedoseofOmeprazole20mgdailyorequivalentdoseofEsomeprazole20mg/Pantoprazole40mg/Rabeprazole20mg inPI-naïvepatients, alongwithRitonavirboosted Atazanavir. PPIs should be administered at least 12hourspriorto Atazanavir/Ritonavir.

2. PPIs are not recommended in PI-experienced patients.

Example: If a PLHIV is on Tenofovir + Lamivudine + Atazanavir/Ritonavir requires to be treated with PPI, S/he should be instruct-ed to take Tab. Omeprazole 20 mg/Esomeprazole 20mg/Panto-prazole 40 mg/Rabeprazole 20 mg OD at 8 AM and Tenofovir + Lamivudine + Atazanavir/Ritonavir after 8 PM.

H2 receptor antagonists are not recommended with Tenofovir+Lamivudine+Atazanavir/Ritonavircombination.


Adverse effects Apart fromthePI-classspecificside-effects likehyperglycaemia,fat maldistribution, hyperlipidaemia (especially with Ritonavirboosting).Theuniqueside-effectsofAtazanavir include indirect hyperbilirubinaemia (producing yellow discolouration of eyes), skinrash,prolongationofPRintervalandnephrolithiasis.

Prolongation of P-R and Q-Tc interval in the ECG can occur.So PR interval need to be monitored in patients with knownconduction defects orwith concurrent use of other drugs thatalter conduction abnormalities (like diltiazem, clarithromycin,cisapride, ketoconazole etc.). However, routine ECG beforestartingAtazanavirbasedARTisnotrecommended.

Atazanavir inducedurolithiasis is also reported; presumablydueto precipitationof thedrug resulting in crystalluria in amanneranalogustoIndinavir.

Storage Roomtemperature(below30degrees)

Rifabutin

Class Anti-tuberculousagentNACO Formulation Tablet 150 mg

ConcurrentusewithATV/r(nochange),Rifabutindose150mgoncedaily3x/wk

RifabutinAUC↑by303%Contraindication AllergytorifampicinSafety in pregnancy Limiteddatainpregnancy.Notteratogenicinrats/rabbitsPrecautions AllergytorifamipicinFood noneInteractions Rifabutinreduceslevelsofwarfarin,barbiturates,benzodiazepines,

beta-blockers,chloramphenicol,clofibrate,oralcontraceptives,corticosteroids,cyclosporine,diazepam,dapsone,digitalis,doxycycline,haloperidol,oralhypoglycaemics,ketoconazole,methadone,phenytoin,quinidine,theophylline,trimethoprim,verapamil.

DrugsthatinihibitcytochromeP450andprolongsthehalflifeofRifabutin:PIsandDelavirdine,erythromycin,clarithromycin(56%increase),andazoles(fluconazole,itraconazole,ketoconazole).

Adverse effects Common:brown-orangediscolorationofsecretions:urine,tears,saliva,sweat,stool,skin.Infrequent:Rash,GIintolerance,neutropenia.Rare:flu-likeillness,hepatitis,hemolysis,headache,thrombocytopenia,myositis.

Uveitisisdose-related(usually>450mg/day)orwithstandard300mg/daycombinedwithdrugsthatincreaserifabutinlevels(mostPIs,clarithromycin,fluconazole)

Storage Roomtemperature(15-30degreesC).


Recommendations for Co administering Antiretroviral Drugs with RIFABUTIN – 2007

Non-nucleoside reverse-transcriptase inhibitors

Antiretroviral dose change

Rifabutin dose change

Comments

Efavirenz Nochange___to450-600mg(dailyorin-termittent)

RifabutinAUC¯by38%.EffectofEfavirenz+proteaseinhibitor(s)onRifabutinconcentrationhasnotbeenstudied.Efavirenzshouldnotbeusedduringthe1st trimester of pregnancy.

Nevirapine NochangeNochange(300mgdailyorthrice-weekly)

RifabutinandNevirapineAUCnotsignificantlychanged.

Dual protease inhibitor combinations

Antiretroviral dose change

Rifabutin dose change

Comments

Lopinavir/ritonavir ä)

Nochange___ to 150 mg everyotherdayor3x/week

RifabutinAUCby303%;25-O-des-acetylRifabutinAUCby47.5fold.

Ritonavir (any dose) with saquinavir, indinavir, am-prenavir, fos-amprenavir, atazanavir, tipranavir or darunavir

Nochange____ to 150 mg everyotherdayor3x/week

RifabutinAUCand25-O-des-acetylrifabutinAUC,byvaryingdegrees.

ANNEX V:


Treatment education information for Second line ART patients

REMEMBERTHAT

Ifyoumissdoses(even2doseinamonth)FURTHER DRUG RESISTANCEwilldevelop.ThisisbadforyouastheseSecondlinedrugswillstopworking.

Drugsmustbetakenasprescribedwithfood,anddonotmissanydose

Ifyouforgetadose,donottakeadoubledose.

IfyoustoptakingtheART,youwillbecomeillwithinmonths.

Donotshareanyofthedrugswithyourspouse,familyor friends.

Ifyoufinditdifficulttotakeyourpills,gobacktotheARTcenteranddiscussthiswiththedoctorandcounselor.Askforsupportfromyourtreatmentsupporter,family,friends,NGOandpositivenetwork.

Remember : Adherence is under your control

Note:Thecolor,shapeandsizeofARVdrugsmaybedifferentduetodifferentsuppliereachyear.

It is common to have side effects. They will usually go away in a few weeks. You can ask doctor to give you some medication to help you make it better. If you have side effects, do the following:

If you have Do the followingNausea TaketheARVpillswithfood.Diarrhoea Keepdrinkingandeating,donoteatspicy

food/chilies.Musclepain,fatigue Thesewillgoaway.

Inauseaordiarrheapersistsorgetsworse,reporttotheARTcenter.

Seekcareurgentlyif:

• Yelloweyeswithhighfever,headache,runningnoseandbodyache.

• Missedperiods/possibilityofpregnancy.

• Severeabdominalpains.

• Extremepalenessofface,handsoreyes.

• Fatigueandshortnessofbreath.

Note:Remembertotakeyourcotrimoxazoleprophylaxistableteveryday,ifthedoctorprescribesit. Alwaysusecondomduringsex. Donotstopanydrugsbyyourself.

ANNEX VI:


Phone:CallARTcentreifyouhaveanyquestionsor problems.(9AM–4PM)

Phone:After4PM,ContactthehospitalEmergencynumber.

Phone:Callthelocalpositivenetworknumberforsupport.

NationalAIDSControlOrganisation MinistryofHealth&FamilyWelfare GovernmentofIndia,9thFloor,ChandralokBuilding 26,Janpath,NewDelhi–110001,India Tel:011-23325343,011-23731774,011-23731778,Fax:011-23731746 E-mail:[email protected]


ANNEX VII (A) – VIRAL LOAD TEST REQUISITION FORM

Annex VII (a)-Viral Load Test Requisition FormVL-1 National AIDS Control Organization Accession NumberPage-1 HIV-1 Plasma Viral Load Test Reauisition Form For Testing Lab Use Only

To be �lled out by the MO/Nurse/Lab technicion ART Center Information Patient SectionART Center Name : Name : _________________ Patient ID # : ___________________Address : _______________________ Patient Name : _________________District : _________ State : _________ Sex : M / FTelephone # : ____________________ Age : ____________ Previous HIV-1 Plasma Viral Load Test Results from ART CenterBaseline : 6 Months: Other (please Explain ): Relevant Clinical DetailsLatest CD4 Count,with date : _____________________________

Earlier HIV-1 PVL Test Performed ? Y / N Date Of Earlier HIV-1 PVL : ____ ____ _____ dd mm YY

Result of Earlier HIV-1 PVL Testing (If Performed ) : _____________________________________Manufacturer Of Previous HIV-1 PVL Test : __________ Assay/Kit used : ___________________

Any infection or immunization in the past 4 weeks ? Y / N HIV-1 PVL Specimen CollectionCollection Date : _______ ________ _______ Collection Time : _______________ Date Month YearName Of MO/Nurse?Lab Technician : _______________ Signature : ________________________

Signature Of ART Nodal Officer : ____________________ Stamp :__________________________To Be �lled out by the ART lab technician carrying the specimens For Lab Technician Couriering the SpecimenName of Lab Technician In-Charge : ___________________________________________________Name of ART Center : _______________________________________________________________

Date Of Specimen Transport to Lab : ______ _____ _____ Time Of Departure : ________ Day Month Year

Signature :To Be �lled out by laboratory - For Laboratory Use OnlyDate Specimen Received ( dd/mm/yy):________________ Time Received : _____________

Specimen received in the acceptable condition : Y / N (Please Circle )If No,list the state of specimen received :Unlabeled/Mislabeled/Insufficient/Inappropriate/Invalid/Other

Stamp:Name Of Lab In-Charge : ________________________Signature : ____________________________________


ANNEX VII (B) – COBASAMPLICOR REPORTING FORMAT

Annex VII(b) - Cobas Amplicor Reporting FormatVL-1 Lab NamePage 2 Address (Street ,District,State) Lab Phone Number

HIV-1 Plasma Viral Load Result Form Cobas Amplicor

Accession Number/Lab Registration Number : ________________________________

Patient ID Number : _______________________________________________________

Date Specimen Tested(dd/mm/yy):__________Date Of Report (dd/mm/yy):____________

Test Kit Name : Cobas Amplicor HIV-1 Monitor Test ,Version 1 Manufacturer : ____________Version : _______________________

ResultHIV-1 RNA Copies/ml

Log-Transformation :

Notes : HIV-1 Quantization by Cobas AmolicorHuman Immunodeficiency virus(HIV) is the etiologic agent of Acquired immunodefiency Syndrome(AIDS).

Quantitative measurements of HIV Viremia in the peripheral blood have shown that higher virus levels

may be correlated with increased risk of clinical progression of HIV Disease.

Interpretation : This procedure can detect virions associated HIV-1 RNA plasma at concentrations as 50

RNA copies/ml to 750,000 HIV-1 RNA copies/mL.Low viral load values may occur as "False positives"and

have been documented in the plasma of uninfected persons or persons infected with other RNA viruses

that resamble HIV(e.g.HTLV).Therefore,caution must be exercised when such a result is obtained on a

specimen of a patient not confirmed as being infected with HIV(through EIA,Western Blot,Or HIV DNA

Assays).

The minimum reliable and significant change in measurement(as compared to baseline value or

previous test value)is a 3-fold(0.5 log) change.

Recommendations:A positive viral load result must always be correlated with clinical hitory and HIV

status of the patient.The cobas Amplicor HIV-1 Monitor test 1.5 is not intended to be used as a diagnostic for HIV-1 infection.This test is not intended for HIV-2 Patients. It is recommended that the follow up viral load testsbe repeted at the same laboratory with the same technique/procedure in order to caompare changes in subsequent.

Name Of lab in-charge : ________________________ stamb of lab in-charge :

signature Of lab In-charge : __________________

Not valid for medical legal purposes


ANNEX VII (C)– TAQMAN REPORTING FORMAT

Annex VII(c) - Taqman Reporting FormatVL-1 Lab NamePage 2 Address (Street ,District,State) Lab Phone Number

HIV-1 Plasma Viral Load Result Form Cobas Taqman

Accession Number/Lab Registration Number : _________________________________________

Patient ID Number : ________________________________________________________________

Date Specimen Tested(dd/mm/yy):__________Date Of Report (dd/mm/yy):____________

Test Kit Name : Cobas Taqman HIV-1 Test Manufacturer : _____________Version : _______________________



Notes : COBAS TaqMan HIV-1 TestHuman Immunodeficiency virus(HIV) is the etiologic agent of Acquired immunodefiency Syndrome(AIDS).



Interpretation : This procedure can detect virions associated HIV-1 RNA plasma at concentrations low as 47

RNA copies/ml to 10,000,000 HIV-1 RNA copies/mL.Low viral load values may occur as "False positives"and


that resemble HIV(e.g.HTLV).Therefore,caution must be exercised when such a result is obtained on a


Assays).

The minimum reliable and significant change in measurement(as compared to baseline value /



status of the patient.The cobas Taqman HIV-1 test 1.5 is not intended to be used as a

dianostic test for hiv-1 infection.This test is not intended for HIV-2 Patients.

It is recommended that viral load tests be repeted at the same laboratory with the same

technique/procedure in order to caompare changes in subsequent viral load counts.Name Of lab in-charge : ________________________ stamb of lab in-charge :




ANNEX VII (D) – VIRAL LOAD RESULT FORM, AMPLICOR HIV MONITORING, V1.5

Annex VII(d) - Viral Load Result Form,Amplicor HIV Monitoring,V1.5VL-1 vvvv Lab NamePage 2 Address (Street ,District,State) Lab Phone Number

HIV-1 Plasma Viral Load Result Form Amplicor HIV Monitoring,version 1.5

Accession Number/Lab Registration Number : _________________________________________

Patient ID Number : ________________________________________________________________

Date Specimen Tested(dd/mm/yy):__________Date Of Report (dd/mm/yy):______________________

Test Kit Name : Amplicor HIV-1 Monitor Test ,Version 1.5 Manufacturer : ____________Version : _______________________



Notes : HIV-1 Quantization by amplicor HIV Monitor Test,Version 1.5Human Immunodeficiency virus(HIV) is the etiologic agent of Acquired immunodefiency Syndrome(AIDS).



Interpretation : This procedure can detect virions associated HIV-1 RNA plasma at concentrations low as 50

RNA copies/ml to 750,000 HIV-1 RNA copies/mL.Low viral load values may occur as "False positives"and


that resemble HIV(e.g.HTLV).Therefore,caution must be exercised when such a result is obtained on a


Assays).

The minimum reliable and significant change in measurement(as compared to baseline value /



status of the patient.The Amplicor HIV-1 Monitor test 1.5 is not intended to be used as a

dianostic test for hiv-1 infection.This test is not intended for HIV-2 Patients.

It is recommended that follow up viral load tests be repeted at the same laboratory with the same technique/procedure in order to caompare changes in subsequent viral load .

Name Of lab in-charge : ________________________ stamb of lab in-charge :




ANNEX VIII

Process for External Quality Assessment for the laboratories performingHIV-1 Viral Load Testing

Introduction

ProcessforExternalQualityAssessmentforthelaboratoriesperformingHIV-1ViralLoadTestingwillinclude4surveysinacalendaryeartotheNACOidentifiedcentresforperformingHIV-1ViralLoadTestingfortheSecondlineinitiative.

Thiswillserveasanimportanttool intheprocessofcontinuousqualityimprovementintheselaboratories.

Confidentiality

ParticipantswillbegivenaParticipantNumbertobeusedasareferenceinallcorrespondence.Atnotimeandundernocircumstancesistheidentityofaparticipatinglaboratoryrevealed.Reportreviewerswhoassessresultsandprovidecomments/discussionsandaneducationalcomponentforeachreportareunawareoftheidentityofparticipants.

Participating Laboratories:

NameofLaboratory&ContactPersonofeachparticipatinglabwouldbeprovidedtoRCPA

EQAS coordinating laboratory in India

NACOhasdesignatedNARItobetheEQAScoordinatinglaboratoryforVLEQASinIndia.

NARI, Pune would take on the responsibility for ensuring that the EQAS programmeis successfully and regularly implemented with active participation of testing labs bycoordinating,monitoring,supervising,training,andprovidingtroubleshootingsupportfortheVLEQASrunsheldatregularquarterly intervals.RocheIndiawouldsupportNARI inthisactivityandcoordinatewithRCPAAustraliaandtheparticipatingcentersforallrelatedactivitiesincludingbutnotlimitedtothedeliveryoftheEQASspecimenstotheselabsforproficiencytestingfourtimesayearatpredeterminedschedules.RocheIndiawouldalsoprovidecoordinationtrainingandtroubleshootingsupporttoNARIasandwhenrequiredfortheNACOVLlabsinthisentireactivity.NARIwouldsubmitformalquarterlyreportstoNACOontheperformanceoftheNACOVLlaboratoriesintheVLEQAS.

Testing

Participants should test specimens in the same manner as patient specimens.

(1)The specimens should be tested with the laboratory’s regular patient workload bypersonnelwhoroutinelyperformthetestinginthelaboratory.

(2)Theparticipantshouldtestspecimensthesamenumberoftimesthatitroutinelytestspatientspecimens.

(3)Theparticipantshouldmaintainacopyofallrecords,includingacopyofthecompletedquestionnaire,torecordproficiencytestingresults.


(4)The results sheet should be signed by the analyst and the laboratory manager,documenting that proficiency testing specimens were tested in the same manneras patient specimens, the report reviewed, results discussed and action taken (ifappropriate).Thisdocumentationshouldbekeptforaminimumofthreeyearsfromthedateoftheproficiencytestingevent.

Specimen Delivery

ThesurveypanelswillbesenttoRocheDiagnosticsIndiafromRCPAQualityProgramPvt.Limited,Australiainthefrozenconditions

UponarrivalthesepanelswouldcheckedfortheshippingconditionsbyanAuthorizedpersonofRocheandsupplementedwithadditionaldryice

4surveys(1surveyperquarter)eachconsistingof3specimenswillbesentouttoeachparticipatinglaboratoryeachcycleofsurveys.

ThespecimenswillbesentoutatthestartofthesurveyanddeliveredbyRocheDiagnosticspersonneltotheindividuallaboratoriestoensureeaseoflogisticsandthatthespecimenintegrityismaintained.

Upondelivery,thespecimensaretobefrozenat-70°Cor-80°Cuntiltheappropriatequestionnaireisreceivedviaemail.Itisessentialthatspecimensarefrozenimmediatelyuponreceiptandstoredinafreezerwhichisnot a frost free instrumentordoesnothaveadefrostcycle.

Specimensmaycontainvirulentpathogensandmustbetreatedwiththesamedegreeofcautionasroutinediagnosticspecimens.Specimensareissuedtoparticipantsontheunderstandingthattheywillbeusedforqualityassurancepurposesandthattheywillbetestedbystafftrainedtohandleequivalentclinicalspecimens.

Survey Process

ReceiveopensurveyemailalertfromNACO

ParticipanttoprintsurveyQuestionnaire

Testrelevantsurveyspecimens

SubmitresultsviaemaildirectlytoRCPAbythesurveyduedatewithacopymarkedtoNACO

RCPAwillsendtheassessmentreporttotherespectiveparticipatinglaboratorywithacopymarkedtoNACO

NARIPunewillsubmittoNACOformalreportsquarterlyontheEQASperformanceoftheNACOviralloadlabs


Survey Questionnaires

Participantsaregiven18daystoperformtestingandsubmitsurveyresults.

Instructionsareoneachquestionnaireexplainingwhatisrequired.PleasecontacttheNARIifyoudonotunderstandanyaspectofthequestionnaire.

Feedback from participants is encouraged and a ‘Compliments, Concerns,Suggestions’ section is in each survey questionnaire, so that participants canimmediatelyprovidefeedbackforspecificsurveys,aswellastheoverallProgramme.

Disposal of Material

Anypartofspecimenswhichisnotusedbytheparticipantshallbedestroyedinthemannerrequiredbyanylaworregulatoryagencyforthedisposalofpotentiallybio-hazardouswaste.

Late Return of Completed Questionnaires (Results)

Lateresultswilldelayreportpreparation.Ifacompletedquestionnairearrivesafter all data hasbeenenteredandcollationofdatahascommenced,thereceivedquestionnairewillbemarked LATE andthefinalreporttoNARIfromRCPAwillnotbeamendedtoincludetheselate results.

Survey Reports

Surveyreportsarepresentedinthefollowingformat:-

•Section One willcontainaParticipantPerformanceTable.Thistableidentifiesparticipantsreturning results inconsistent with consensus of ≥80% of participating laboratories,omissionofkitdetails,useofexpiredkits,occurrenceoftranscriptionerrors,inconsistentorincompletedata,inappropriateinterpretativecommentselectionandnonidentificationof clerical errors.

•Section Two containsthecollatedreport,whichisasummaryofparticipantresults,andincludesdiscussion/commentfromascientist/pathologistwithHIVexpertise.

5.55.04.54.03.53.02.52.01.51.00.50.0

Valu

es (I

U/m

L Lo

g 10)

ParticipantResults ParticipantResults

MedianRange-0.25Range +0.25Specimen2A

MedianRange-0.25Range +0.25Specimen2B

Valu

es (I

U/m

L Lo

g 10)

HIV RNA Quantitation (n=11) - Specimen 2A HIV RNA Quantitation (n=8) - Specimen 2B6.56.05.55.04.54.03.53.02.52.01.51.00.50.0


ANNEXURE IX- SECOND LINE REPORTING

1 SL + AL: SACEP REGISTER FOR ALTERNATIVE FIRST LINE & SECOND LINE ART (ADULTS AND CHILDREN)(SACEP coordinator at CoE/pCoE and data manager at ART plus centre should maintain

this register)These columns should be on left half of register

Month: Year:

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Sl. N

o (S

ACE

P re

gist

rati

on N

o) #

.

ART

Reg

istr

ation

Num

ber

Pati

ent N

ame

Age

Gen

der

Add

ress

Con

tact

Num

ber

Nam

e of

refe

rrin

g A

RT C

entr

e

Cont

act n

o. o

f ref

erri

ng A

RT C

entr

e

Nam

e &

Con

tact

Num

ber

of N

GO

s lin

ked

to re

ferr

ing

ART

Ce

ntre

(CCC

/DLN

/TI/

othe

r lo

cal N

GO

s)

Dat

e of

Ref

erra

l (Fi

rst e

lect

roni

c re

ferr

al fr

om A

RT c

entr

e se

ekin

g ap

poin

tmen

t)

App

oint

men

t Giv

en (

If Y

es-D

ates

/If N

o –

Reas

on )

Dat

e of

act

ual a

sses

smen

t by

SACE

P

Rea

son

For

Refe

rral

*

Late

st C

D4

(wit

h da

te) a

t the

tim

e of

SA

CEP

asse

ssm

ent

(not

mor

e th

an o

ne m

onth

old

))

Clin

ical

Sta

ging

at ti

me

of S

ACE

P as

sess

men

t

Func

tion

al S

tatu

s at

tim

e of

SA

CEP

asse

ssm

ent

(WA

B)

Whe

ther

VL

testi

ng re

com

men

ded

or n

ot b

y SA

CEP

(Y/N

)

If V

iral

Loa

d re

com

men

ded,

resu

lts

(wit

h da

te)/

Gra

de o

f to

xici

ty

Reco

mm

enda

tion

s of

SA

CEP

(fee

dbac

k to

be

sent

to th

e re

ferr

ing

ART

cen

tre&

SA

CS) *

*

Pati

ent

Care

giv

er

* 1.Suspectedtreatmentfailure2.Sideeffectsofdrugs3.OnSecondlineARTfromPrivate4.Others

**1.RecommendedforSecondlineART2.SubstitutionwithPIcontainingregimen3.SubstitutionofNRTIbackbone4.Substitutionwithotherregimen–(Specifyregimencode)5.Managementofcomplicatedcases/others6.ReferredbacktoARTcentreforreviewafter1/3/6months

***1.Ifviralload<400copies/ml,noOI,nosideeffects-transferoutthepatientbacktothereferringcentre2.ifviralload>400copies/mlat6monthafterSecondlineARTinitiationandnoOI/sideeffects,stilltransferthepatienttothereferringcentreandcallthepatientbackforviralloadafteranothersixmonths(12thmonthfromthetimeofinitiationofSecondlineART)

****Forpatientswithviralloadmorethan400copies/mlatSecondviralloadtesting(at6thmonthafterSecondlineARTinitiation)


These columns to be on the right side of the register

21 22 Follow up of patients on Second line 31

23 24 25 26 27 28 29 30

Dat

e of

initi

ation

of S

econ

d lin

e/A

lter

nati

ve

Firs

t lin

e A

RT

Reco

mm

ende

d re

gim

en (i

ndic

ate

regi

men

nu

mbe

r as

per

NA

CO A

RT G

uide

lines

)

Any

Maj

or O

I obs

erve

d w

hile

on

Seco

nd li

ne

ART

Dat

e of

vir

al lo

ad te

sting

at 6

mon

th a

fter

in

itiati

on o

f Sec

ond

line

ART

Resu

lt o

f vir

al lo

ad te

sting

at 6

mon

ths

Reco

mm

enda

tion

s of

the

SACE

P aft

er S

ec-

ond

vira

l loa

d **

*

Aft

er in

itiati

on o

f Sec

ond

line,

whe

ther

Pa-

tien

t ref

erre

d ba

ck to

the

refe

rrin

g A

RT c

entr

e as

per

gui

delin

es a

t six

th m

onth

(yes

/no)

Dat

e of

refe

rral

bac

k to

the

noda

l ART

cen

tre

Vir

al lo

ad te

sting

at 1

2 m

onth

( if r

ecom

-m

ende

d by

SA

CEP)

****

Reco

mm

enda

tion

s of

SA

CEP

at12

th m

onth

vi

ral l

oad,

if a

pplic

able

Repeat Viral loads (with date) for patients not eligible for Second line drugs at First SACEP review (As per guidelines, those whose VL is between 400- 5000 copies/ml)

1 2 3 4 5 6


2 AL: ALTERNATIVE FIRST LINE FORMAT FOR SACEP MEETING (ADULT & CHILDREN)

(To be prepared before SACEP meeting and given to all members during the meeting and to be kept at CoE/pCoE/ART plus centre)

Meeting date :

Alternative First line ART

1 2 3 4 5 6 7 8 9 10 11 12 13

Sl. N

o (S

ACE

P re

gis-

trati

on N

o).

ART

Reg

istr

ation

N

umbe

r

Nam

e of

pati

ent

Age

Gen

der

Add

ress

Nam

e an

d ad

dres

s of

re

ferr

ing

ART

cen

tre

ART

sta

rt d

ate

(wit

hin

the

prog

ram

)

ART

sta

rt d

ate

(out

-si

de t

he p

rogr

am)

% A

dher

ence

to F

irst

lin

e dr

ugs

Clin

ical

sta

ge a

t the

ti

me

of a

sses

smen

t

CD4 counts (with date) cells/Cmm

(expandable)

Type

of t

oxic

ity

/sid

e eff

ects

obs

erve

d

Summary -2AL Alternative First line ART Members Present

during the SACEP

Sl. No Name of the regimenNo of

patients1

1

TotalnumberofpatientsreviewedbySACEPforAlternativeFirstlinetreatment

TDF containing regimen (Adult) 2

ATV/r based regimen (Adult) 3

LPV/r based regimen (adult) 4

ABC/3TC+NVP 5

ABC/3TC+EFV

ABC/3TC+LPV/r

ZDV/3TC+LPV/r

d4T/3TC+LPV/r

TDF+3TC+ATV/r(HIV-2/dualtoxicity)

2TotalnumberofpatientsactuallyrecommendedonAlternativeFirstlineART

TDF containing regimen (Adult)

ATV/r based regimen (Adult)

LPV/r based regimen (Adult)

ABC/3TC+NVP

ABC/3TC+EFV

ABC/3TC+LPV/r

ZDV/3TC+LPV/r

d4T/3TC+LPV/r


14 15 16 17 18 19 20 21

Gra

de o

f tox

icit

y

Phot

o do

cum

enta

tion

(Y

es/n

oO

Any

OI’s

repo

rted

Nam

e of

dru

g (d

4t/A

ZT/

NV

P or

EFV

or

any

othe

r A

RV )

whi

ch (p

roba

bly)

ca

used

toxi

city

– s

peci

fy

Whe

ther

reco

mm

ende

d fo

r A

lt F

irst

line

? (Y

es/

No)

If recommended for Alt First line?

Rem

arks

Adult Regimen Paediatric Regimen

TDF

base

d Re

gim

en

ATV/

r ba

sed

Regi

men

Oth

er re

gi-

men

ABC

/3TC

+ N

VP

ABC

/ 3T

C+

EFV

ABC

/ 3T

C+

LPV/

r

ZDV/

3TC

+ LP

V/r

d4T/

3TC+

LP

V/r


Second line ART

1 2 3 4 5 6 7 8 9 10 11 12

Sl. N

o (S

ACE

P re

gist

ratio

n N

o).

ART

Reg

istr

ation

no.

Nam

e of

pati

ent

Age

Gen

der

Add

ress

Nam

e , a

ddre

ss o

f ref

er-

ring

ART

cen

tre

ART

sta

rt d

ate

(wit

hin

the

prog

ram

me)

ART

sta

rt d

ate

(out

side

th

e pr

ogra

mm

e )

Adh

eren

ce to

Fir

st li

ne

drug

s

CD4 counts (with date)

Cells/cmm all values to be

given

Reco

mm

ende

d fo

r V

iral

Lo

ad T

est b

y SA

CEP

(Y/N

)

New cases

Follow up cases

NewCases:ThosePLHIVwhoarebeingreferredtoSACEPfortheFirsttimeandre-referredcaseswhowerepreviouslynotgivenappointmentorwerenotpreviouslyeligible(<400copies/ml).

Followupcasesincludes:

• ThosePLHIVwhohavecomeforreviewwiththeirFirstVLreportor

• RepeatVLresultsafterinitiationofSecondline(6th/12thmonth),or

• ThosePLHIVswhowerenoteligibleearlierandhavecomeforreviewofrepeatviralloadsresultsbySACEP(400-5000copies/ml)

13 14 15 16

Vira

l Loa

d re

sult

with

dat

e

Clin

ical

Sta

tus

(OI,

Clin

i-ca

l sta

ging

)

Whe

ther

reco

mm

ende

d fo

r Se

cond

line

ART

?

(Yes

/No)

Rem

arks

2 SL : SECOND LINE FORMAT FOR SACEP MEETING (ADULT & CHILDREN )

(To be prepared before every SACEP and given to members during the meeting &be kept at CoE/pCoE/ART plus Centres)


2SL Summary -Second Line ART Members Present during the SACEP

Sl. No No of

patients1

1Totalno.ofpatientsreferredtoSACEPforsuspectedtreatmentfailure

2

2Totalno.ofpatientssupposedtoattendSACEPforsuspectedtreatmentfailure

3

3TotalNumberofpatientsactuallyreviewedbySACEPforsuspectedtreatmentfailure

4

4TotalnumberofpatientsrecommendedforViral Load test

5

5TotalnumberofpatientsrecommendedforSecondLineART(AfterVL)

6

6TotalnumberofpatientsactuallyinitiatedonSecondLineART(Afterminimum2counsellingsessions)


3AL+

SL C

OM

BIN

ED M

ON

THLY

REP

OR

TIN

G F

OR

MAT

FO

R S

ECO

ND

& A

LTER

NAT

IVE

FIR

ST L

INE

AR

T(to

be

sent

to N

ACO

by

4th o

f eve

ry m

onth

to S

econ

dlin

e200

8@gm

ail.c

om)

(Pro

vide

d se

para

tely

in E

xcel

form

)

artdrugs@gm

ail.com

,Con

cerned

SAC

S(JD,C

ST),RC

&linked

CoE

/ART

plus/pC

oE)

1. N

ame

of A

RT C

entr

e

2. C

MIS

Cod

e of

ART

cen

tre

(sam

e as

cod

e fo

r Fi

rst l

ine)

3.Nam

eofth

eDistrict

4.Nam

eofth

eState

5.Nam

eofNod

alOfficer

6.Rep

ortforth

epe

riod

Mon

th Y

ear

Seco

nd li

ne A

RT

7. D

etai

ls o

f PLH

IV re

ferr

ed to

SA

CEP

for

susp

ecte

d tr

eatm

ent f

ailu

reA

dult

Child

ren

Tota

l

M

ale

Fem

ale

TS/T

GM

ale

Fem

ale

7.1Cu

mulati

venum

berofPLH

IVre

ferred

toSAC

EPfo

rassessmen

tatthe

be

ginn

ingofth

ism

onth

7.2Num

berofnew

PLH

IVre

ferred

toSAC

EPfo

rassessmen

tduringthis

mon

th

7.3

Cum

ulati

ve n

umbe

r of

PLH

IV re

ferr

ed to

SA

CEP

for

asse

ssm

ent a

t the

en

d of

this

mon

th =

7.1

+ 7

.2

7.4a

Cum

ulati

venum

berofpati

entsre

ferred

from

thisCoE

/ART

pluscentre

(The

repo

rting

cen

tre)(o

utof7

.3)

7.4b

Cum

ulati

venum

berofpati

entsre

ferred

from

referringART

cen

tres

linkedtoth

isCoE

/ART

plus(outof7

.3)

7.4cCum

ulati

venum

berofpati

entsgiven

app

ointmen

tforSAC

EPre

view

at

endofth

ism

onth(ou

tof7

.3)

7.4d

Cum

ulati

venum

berofpati

entsactua

llyre

view

edbySA

CEPatend

of

thism

onth(ou

tof7

.4c)

7.4e

Cum

ulati

venum

berofPLH

IVfo

undeligiblefo

rViralLoa

d(outof7

.4d)


7.4fCum

ulati

venum

berofPLH

IVactua

llyund

erwen

tVira

lLoa

d(outof

7.4e

)

8.1Cu

mulati

venum

berofPLH

IVfo

undeligiblefo

rSecond

line

atb

eginning

ofth

ism

onth

8.2Num

berofPLH

IVfo

undeligiblefo

rSecond

line

duringthism

onth

8.3

Cum

ulati

ve n

umbe

r of

PLH

A fo

und

elig

ible

for

Seco

nd li

ne a

t the

end

of

this

mon

th =

8.1

+ 8

.2

8.4Cu

mulati

venum

berofpati

entseverstartedon

Secon

dlin

eART

(Num

-be

ratth

ebe

ginn

ingofth

ism

onth)(8.7ofp

reviou

smon

th)

8.5Num

berofnew

pati

entsstarted

onSecond

line

ART

duringthism

onth

8.6Num

berofpati

ents“restarted“onSecond

line

ART

duringthism

onth

8.7

Cum

ulati

ve n

umbe

r of

pati

ents

eve

r st

arte

d on

Sec

ond

line

ART

(Num

-be

r at

the

end

of th

is m

onth

) = 8

.4+8

.5+8

.6

9.1Cu

mulati

venum

berofpati

entsonSecond

line

who

diedsincethe

beginn

ingofth

eprog

ramme

9.2a

Cum

ulati

venum

berofpati

entsonSecond

line

who

are“tran

sferred

out”to

otherCOE/ART

plus

9.2b

Cum

ulati

venum

berofpati

entsonSecond

line

who

are“tran

sferred

out”to

thereferringcentres(ART

cen

tres)

9.2cCum

ulati

venum

berofpati

entsonSecond

line

who

are“tran

sferred

in”(fromotherCOE/ART

plus)

9.3Num

berofallpa

tientson

Secon

dlin

etreatm

entw

hosetreatm

ent

statusin

thism

onthis“stop

pedtreatm

ent”

9.4Cu

mulati

veNum

berofpati

entsonSecond

line

who

arelo

stto

follo

w-up

(LFU

)

9.5Cu

mulati

veNum

berofpati

entsonSecond

line

treatm

entw

hodidnot

returnto

theART

cen

tre(Defau

lter)/w

hosetreatm

entstatusis“MIS”inth

is

mon

th

9.6

Tota

l num

ber

of p

atien

ts a

live

and

on S

econ

d lin

e A

RT (O

T) a

t the

end

of

this

mon

th =

8.7

+ 9.

2c -

(9.1

+9.2

a+9.

3+9.

4+9.

5)

9.7a

Outof9

.6,the

num

berofpati

entsonSecond

line

ART

initiated

on

DOTSth

ism

onth


9.7b

Outof9

.6,the

num

berofpati

entsonSecond

line

ART

initiated

on

non-DOTSanti

-tub

erculosistreatm

entthismon

th

9.7cOutof9

.6,the

totaln

umbe

rofpregn

antw

omen

onSecond

line

ART

thism

onth

Alt

erna

tive

Fir

st li

ne A

RT

10.1Cu

mulati

venum

berofPLH

IVre

ferred

toSAC

EPfo

rassessmen

tatthe

be

ginn

ingofth

ism

onth

10.2Num

berofnew

PLH

IVre

ferred

toSAC

EPfo

rassessmen

tduringthis

mon

th

10.3

Cum

ulati

ve n

umbe

r of

PLH

IV re

ferr

ed to

SA

CEP

for

asse

ssm

ent a

t the

en

d of

this

mon

th(1

0.1+

10.2

)

10.3aNum

berreferred

from

CoE

/ART

plus(The

repo

rting

cen

tre)(o

utof

10.3

)

10.3bNum

berreferred

from

otherART

cen

tres(o

utof1

0.3)

11.1Cum

ulati

venum

berofPLH

IVfo

undeligiblefo

rAlte

rnati

veFirstline

ART

atb

eginning

ofthismon

th(1

1.3ofpreviou

smon

th)

11.2Num

berofPLH

IVfo

undeligiblefo

rAlte

rnati

veFirstlineART

during

thism

onth

11.3Totalnum

berofPLH

IVfo

undeligiblefo

rAlte

rnati

veFirstlineART

till

theen

dofth

ism

onth(11.1+

11.2)

12.1Cum

ulati

venum

berofpati

entseverstartedon

Alte

rnati

veFirstline

ART

(Num

beratth

ebe

ginn

ingofth

ism

onth)

12.2Num

berofnew

pati

entsstarted

onalternati

veFirstlineART

during

thism

onth

12.3

Cum

ulati

ve n

umbe

r of

pati

ents

eve

r st

arte

d on

Alt

erna

tive

Fir

st li

ne

ART

(Num

ber

at th

e en

d of

thi

s m

onth

) =12

.1+1

2.2

13.1Cum

ulati

venum

berofpati

entsonalternateFirstlinewho

diedsince

thebe

ginn

ingofth

eprog

ramme

13.2aCu

mulati

venum

berofpati

entsonAlte

rnati

veFirstlinewho

are

“transferred

out”tootherCoE

/ART

PlusCe

ntres

13.2bCu

mulati

venum

berofpati

entsonAlte

rnati

veFirstlinewho

are

“transferred

out”toth

ereferringART

cen

tre

13.2cCu

mulati

venum

berofpati

entsonAlte

rnati

veFirstlinewho

are

“transferred

in”from

othercen

tres(C

oE/ART

plus)


13.3The

num

berofallpa

tientson

Alte

rnati

veFirstlinetreatm

entw

hose

treatm

entstatusinth

ism

onthis“stop

pedtreatm

ent”

13.4Cum

ulati

veNum

berofpati

entsre

ceivingAlte

rnati

veFirstlinewho

are

lostto

follo

w-up(LFU

)

13.5The

num

berofpati

entsonAlte

rnati

veFirstlinetreatm

entw

hodidnot

returnto

theART

cen

tre(Defau

lter)/,who

setreatm

entstatusis“MIS”in

thism

onth

13.6

Tot

al n

umbe

r of

pati

ents

aliv

e an

d on

Alt

erna

tive

Fir

st li

ne A

RT=

12.3

+13.

2c-(

13.1

+13.

2a+1

3.3+

13.4

+13.

5)

13.7Outof1

3.6,th

enu

mbe

rofpati

entsonAlte

rnati

veFirstlineART

initi-

ated

onDOTSth

ism

onth

13.8th

enu

mbe

rofpati

entsonAltFirstlineART

initiated

onno

n-DOTS

anti-tube

rculosistreatm

entthismon

th

13.9th

etotaln

umbe

rofpregn

antw

omen

onAlte

rnati

veFirstlineART

this

mon

th

14. T

reat

men

t A

dher

ence

N

umbe

r

14.1aOfa

llpa

tientswho

areonSecond

line

ART

thism

onth(9

.6),thenu

mbe

rwho

haveNOTbe

enassessedforad

herence

(ref

er g

uide

line)

14.1bOfa

llpa

tientson

Secon

dlin

eART

(9.6)thismon

thand

who

havebe

enassessedforad

herence,how

man

yha

d95

%

adhe

renceorbett

er(referguide

line)

14.2aOfa

llpa

tientswho

areonalternati

veFirstlineART

thism

onth(1

3.6)th

enu

mbe

rwho

haveNOTbe

enassessedfor

adhe

rence(referguide

line)

14.2bOfa

llpa

tientson

alte

rnati

veFirstlineART

(13.6)th

ism

onthand

who

havebe

enassessedforad

herence,how

man

yha

d95

%adh

eren

ceorbe

tter(referguide

line)

15 a

. Pri

mar

y Re

gim

en o

f PLH

IV s

tart

ed o

n Se

cond

line

/Alt

erna

tive

Fir

st li

ne A

RT a

t the

end

of t

he m

onth

Regi

men

Adu

lt

Pedi

atri

csTo

tal

Teno

fovir+Lam

ivud

ine+Nevira

pine

11

2

Teno

fovir+Lamivud

ine+Efavire

nz1

12

Zido

vudine

+Lam

ivud

ine+Atazan

avir/Rito

navir

11

2

Zido

vudine

+Lam

ivud

ine+Lopina

vir/Ritona

vir

11

2

Teno

fovir+Lamivud

ine+

Atazana

vir/Ritona

vir

11

2


Teno

fovir+Lamivud

ine+Lop

inavir/Rito

navir

11

2

Stavud

ine+Lamivud

ine+Lopina

vir/Ritona

vir

11

2

Stavud

ine+Lamivud

ine+Atazan

avir/Rito

navir

11

2

Aba

cavir+Lamivud

ine+Nevira

pine

11

2

Aba

cavir+Lamivud

ine+Efavire

nz1

12

Aba

cavir+Lamivud

ine+Lopina

vir/Ritona

vir

11

2

Zido

vudine

+Lam

ivud

ine+Lopina

vir/Ritnovir

11

2

Stavud

ine+Lamivud

ine+Lopina

vir/Ritona

vir

11

2

Aba

cavir+Lamivud

ine+Didan

osine+Lopina

vir/Ritona

vir

11

2

Others

11

2

Tota

l 15

1530

15.b

. Tot

al N

umbe

r of

Pati

ents

on

CPT

Prop

hyla

xis

Regi

men

Adu

ltsPe

diat

rics

Cotrim

oxazole(DS)

Cotrim

oxazole(SS)

Cotrim

oxazoleSu

spen

sion

Tota

l num

ber

of p

atien

ts


15.c

. Opp

ortu

nisti

c In

fecti

ons

OI’s

Num

ber

of e

piso

des

of O

Is th

is

mon

thO

I’sN

umbe

r of

epi

sode

s of

OIs

this

mon

th

Adu

lts P

edia

tric

sA

dults

Ped

iatr

ics

1(a)Tub

erculosis(Pulmon

ary)

8Toxoplasmosis

1(b)Tube

rculosis(E

xtra-Pulmo-

nary)

9CM

VRe

tinitis

2 Ca

ndid

iasi

s

10

Bacterial

Infecti

ons(skin)

3Diarrho

ea

11

Herpe

sSimplex

4 PC

P

12

Maligna

ncy

5Herpe

sZo

ster

13Others

6Ba

cterialInfectio

ns(R

espiratory)

14Others

7CryptococcalM

eningitis


4 A

L : L

IST

OF

PATI

ENTS

ON

ALT

ERN

ATIV

E FI

RST

LIN

E A

RT

12

34

56

78

910

1112

1314

1516

17

Sl. No (SACEP registration No).

ART Reg. No.

Name

Age

Sex

Address

Telephone

Date of ART start (1st line)

Current CD4 count

Type

of T

oxic

ity

Probable drug causing toxicity

SACEP recom-mendations

Date of ART start (alternative First line)

Alternative First line Regimen*

Status of patient (OT/MIS/LFU/TO/Death)

To b

e fil

led

by C

oE/P

CoE/

ART

plu

s ce

ntre

onl

y

Clin

ical

Symptom

sLabo

ratory

test

sPa

tien

t ref

erre

d ba

ck to

the

refe

rrin

g A

RT

cent

re (y

es/n

o?)

Dat

e of

refe

r-ra

l bac

k to

the

refe

rrin

g A

RT

cent

re

4 SL

: L

IST

OF

PATI

ENTS

ON

SEC

ON

D L

INE

AR

T

15.d

Wer

e th

ere

any

spec

ific

side

eff

ects

not

ed fo

r Se

cond

line

/Alt

erna

tive

Fir

st li

ne A

RT d

urin

g th

e m

onth

M

ale

Fem

ale

Parti

cula

rsA

dult

Pedi

atri

csA

dult

1. A

ZT In

duce

d A

naem

ia

2.Periphe

ralN

europa

thy

3.Hep

atitis

4.Lipod

ystrop

hy

5.Pancreati

tis

6.SkinRe

actio

n

7.CNSSide

Effe

cts

8. IR

IS


12

34

56

78

910

1112

1314

1516

17

Sr. No.( (SACEP Regn. No)

ART Reg. No.

Name

Age

Sex

Address

Telephone

Date of ART start (1st line)

Current regimen (at the time of SACEP Referral)

CD4

coun

tV

iral

load

at t

he ti

me

of S

ACE

P as

sess

men

t w

ith

date

SACE

P re

com

men

dati

ons

Date of ART start (Second line)

Second line ART regimen initiated

Status of patient (OT/MIS/LFU/TO/Death)

To b

e fil

led

by

CoE/

PCoE

/ART

pl

us c

entr

e on

ly

Baseline

At the time of At the time of referral to SACEP

Baseline

Aft

er 6

m

onth

s on

2nd

Li

ne

Aft

er 1

2 m

onth

s on

2nd

Li

ne

After Baseline VL

Aft

er 6

m

onth

s on

2nd

Li

ne

Aft

er

12

mon

ths

on 2

nd

Line

Pati

ent

re-

ferr

ed

back

to

the

refe

r-ri

ng

ART

ce

ntre

(y

es/

no?)

Dat

e of

re

ferr

al

back

to

the

refe

r-ri

ng A

RT

cent

re

1

2

3

4 5 6 7 8 9 10

Tota

l


5 SL

: CEN

TRE

WIS

E (L

INK

ED C

ENTR

E IN

FOR

MAT

ION

) BR

EAK

UP

FOR

PLH

IV IN

ITIA

TED

ON

SEC

ON

D L

INE

AR

TS.

No

Nam

es

of

Link

ed

ART

Ce

ntre

s

Cum

ula-

tiveno

of

patie

nts

Refe

rred

to

SAC

EP

(7.3

)

Cum

ula-

tiveno

of

patie

nts

givenap

-po

intm

ent

for

SACE

P review

(7

.4c)

Cum

ula-

tiveno

of

patie

nts

actually

review

ed

bySAC

EP

(7.4

d)

Cum

ula-

tiveno

of

patie

nts

elig

ible

for

viralloa

dte

st (7

.4e)

Cumulati

ve

num

ber

of

PLHIVactua

lly

unde

rwen

tVi

ral L

oad

(7.4

f)

Cum

u-lativ

enu

mbe

r of

PLH

A

foun

d el

igib

le fo

r Se

cond

lin

e (8

.3)

Cumulati

ve

num

ber

of

patie

ntsever

star

ted

on

Seco

nd li

ne

ART

(8.7

)

Cum

u-lativ

enu

mbe

r of

pa

tients

on S

econ

d lin

ewho

di

ed (9

.1)

Alivean

don

Secon

dlin

eART

(9.6)

At C

oE/

ART

plus

cent

re

At re

fer-

ring

cen

tre

Tota

l

1

2

3

4

5

6

7

8

9

10 To

tal


ANNEX X



ACKNOWLEDGEMENTS

“The National AIDS Control organisation wishes to acknowledge contributions made by the guidelines team at NACO, Regional Coordinators, Joint Directors of SACS, Program Directors of CoEs, and other contributors in updating these guidelines.

We also acknowledge the technical support provided by World Health Organisation country office for India in developing and updating these 2013 guidelines.

The support of International Training and Education Centre for Health (I-TECH), India for printing these guidelines is also acknowledged”

Documents

NACO | Blended Clinical Training LMS - Table of Contents National... · 2020. 10. 27. · (Current NACO treatment guidelines for First-line ART recommend three drug combination therapy