Indicators for monitoring ARV treatment Indicators for monitoring ARV treatment outcomesoutcomes
Information streams and their relationshipsInformation streams and their relationships
Pharmacovigilance
Severe adverse Events(SAE)
HIVDR
Exposed clients
Naive clients
Patient Monitoring
Switching rates
Survival rates
Failure rates
# SAE/patients on treatment
#patients on treatment
DrugSupply
Management
# pills ordered
TREATMENT POLICY
Patient monitoringPatient monitoring
George Loth – EIP dept, WHO
(UNAIDS/WHO Working Group on global HIV/AIDS/STI surveillance)
Information flow from patient level to International levelInformation flow from patient level to International level
Health Facility & community level; clinic, health centre, hospital
District level; woreda, local government
Sub-national level; province, region
National level; federal
International level
StandardData, Datasets& IndicatorsFor each level
Community
District
Province
National
International
Patient level; or singular, local unit for not patient related data
Patient /Singular unit
District
NationalNational
Healthfacility
Quarterly reports
Cohort analysis
Province Province
District District
Healthfacility
Healthfacility
Healthfacility
Healthfacility
Healthfacility
Patientmonitoring
cards
Information
PATIENT MASTER RECORD CARD FOR ARV [ front]: Unique ARV Number___________________ Year_______________
Name________________________________________ Age ______ Sex_______ Initial Wt (Kg)_______ Transfer-In (Y/N)________
Address (physical / PO Box)______________________________________________________________________________________________
Name of identifiable guardian_____________________________________ Date and place of positive HIV test____________________________
Date of starting 1st line ARV regimen (specify d4t/3TC/NVP formulation) _____________ Reason for ARV: ______________________________
Date of starting alternative 1st line ARV regimen (specify) ____________ Date of starting 2nd line ARV regimen (specify)____________________
Outcome status Of those alive Ambulatory Work/school Sideeffects
ARVGiven
Year Month Date WtKg
A D DF Stop TO Start Sbs Switch Amb Bed Yes No Y N
No. Pills inBottle
P G
ARV notgiven
JanFebMarAprMayJunJulAugSepOctNovDec
Specify reason for ARV therapy (Stage III, Stage IV, CD4 < 200, PTB, EPTB, Transfer-in)
Outcome status: A =alive; D=dead; DF=defaulted and not seen for 3 months; Stop=stopped medication; TO=transferred out to another unitOf those alive: Start=alive and on first line regimen; Sbs=alive and substituted to alternative first line regimen;Switch=alive and switched to a second line regimen because of failure of first line regimen
Ambulatory: Amb=able to walk to/at treatment unit and walks at home unaided; Bed=most of time in bed at homeWork/school: Yes=engaged in previous work / employment or at school; No=not engaged in previous work /employment or not at schoolSide effects: If Yes, specify – YES-PN= peripheral neuropathy; YES-HP=hepatitis; YES-SK=skin rashNo.Pills in bottle: if patient comes at 4 weeks count number of pills in bottle (8 pills or less = 95% adherent)ARV given / not given: tick whether ARV therapy given in the appropriate column P = patient, G = Guardian; if no ARV, then indicate why
Patient cardPatient card
ARVRegistrationNumber
Year Quarter Date ofregistration
Name Sex Age Address Date firststartedARV drugs
Reason forstartingARV drugs
Name ofGuardian
ARVTreatmentUnit
Reason for starting ARV Drugs: Stage III, Stage IV, CD4 count < 200/mm3, Stage II with TLC< 1200/mm3 , Tuberculosis, Transfer-in
ART registerART register
Outcome (provide dates when change from alive) Of those alive Ambulant At work or school Drug adherence > 95%Alive Dead Default Stop Transfer Start Substitute Switch Yes No Yes No Yes No
Alive - alive and on ARV drugs: Dead - whatever the cause: Default - not seen in three months:Stop - stopped treatment due to side effects/other:Transfer - transfer-out to another ARV treatment unit
Start - on first line regimen: Substitute - changed to alternative first line regimen: Switch -changed to second line regimen
Ambulant - yes/no: At work or school - at previous or new employment for adults
Adherence > 95% - pill counts of 8 tablets or less when patient comes for review
ART register - continuedART register - continued
Relevant information for ARVs Relevant information for ARVs
ART Cohort Analysis Report:ART Cohort Analysis Report: at 6 months, 12 months, yearlyat 6 months, 12 months, yearly
Alive and on ARTAlive and on ART On original first-lineOn original first-line Substituted to alternate first-lineSubstituted to alternate first-line Switched to 2nd-line (or higher)Switched to 2nd-line (or higher) Dead, Lost, Transfer Out, Stopped ARTDead, Lost, Transfer Out, Stopped ART Functional statusFunctional status CD4 median or CD4 median or >> 200 200 Picked up meds 6/6 or 12/12 monthsPicked up meds 6/6 or 12/12 months
National/sub-national
Data-warehouse
Health Facility 1 Health Facility 2
HL7
Other AgenciesAcademic
NGOsIndustry
etc.
International AgenciesCentral GovernmentSub-national/districtLocal
HIV Indicators:repository
Other Data Sources
Country's HIS
Software: CRIS, HealthMapper, DevInfo etc.
HL7
Evaluation
Monitoring
Community
Other Data Sources
Schematic representation of IT configuration for monitoring and evaluating in Schematic representation of IT configuration for monitoring and evaluating in countries scaling up HIV services countries scaling up HIV services
ART Needs: Present and Future ART Needs: Present and Future with scaling up and Universal with scaling up and Universal
AccessAccess
UNAIDS/WHO Working Group on global HIV/AIDS/STI surveillance
Estimated ART needs for Africa and Asia
0
2000
4000
6000
8000
10000
12000
years
Tota
l num
ber i
n 0
00
Africa Low
Africa High
Asia Low
Asia High
ConclusionsConclusions
These treatment scenarios suggest that These treatment scenarios suggest that globally between 9.5 and 17.3 million globally between 9.5 and 17.3 million adults (age 15 to 49 years) and between adults (age 15 to 49 years) and between 900,000 and 2.3 million children (age 0 to 900,000 and 2.3 million children (age 0 to 14 years) would require antiretroviral 14 years) would require antiretroviral treatment by 2015. treatment by 2015.
PharmacovigilancePharmacovigilance
Marco Vitoria - WHO, HIV department
(input from M Couper, S Pal – QSM unit, PSM department)
Importance of Pharmacovigilance Importance of Pharmacovigilance (PV) for ARV(PV) for ARV
Impact in selection of preferential/alternative drugs in ART Impact in selection of preferential/alternative drugs in ART guidelinesguidelines
Drug toxicity (important cause of switching specific drugs in 1st Drug toxicity (important cause of switching specific drugs in 1st and 2nd line regimens).and 2nd line regimens).
Life threatening side effects, co-morbidities & co-treatments: Life threatening side effects, co-morbidities & co-treatments: impact on selection of preferential and alternative drugsimpact on selection of preferential and alternative drugs
Efficacy is the major focus of drug clinical trials (short duration Efficacy is the major focus of drug clinical trials (short duration of clinical trials, risk of long term adverse effects)of clinical trials, risk of long term adverse effects)
Available data on drug toxicity are mainly from industrialized Available data on drug toxicity are mainly from industrialized world - different clinical and operational context from developing world - different clinical and operational context from developing countriecountriess
What Information Should be Collected for the What Information Should be Collected for the ARV Drug Adverse Reactions ARV Drug Adverse Reactions
Protocol/Registry?Protocol/Registry?
ABC hypersensitivity reactionsABC hypersensitivity reactions TDF related kidney & bone toxicityTDF related kidney & bone toxicity d4T associated neuropathy & lipodystrophyd4T associated neuropathy & lipodystrophy NVP and SQV/r hepatotoxicity with TB drugsNVP and SQV/r hepatotoxicity with TB drugs AZT associated anaemiaAZT associated anaemia Birth defects and EFVBirth defects and EFV ddI related pancreatitisddI related pancreatitis NRTIs associated lactic acidosisNRTIs associated lactic acidosis
Moving from Adverse Events Reporting to a Moving from Adverse Events Reporting to a Comprehensive Pharmacovigilance Strategy: Which Comprehensive Pharmacovigilance Strategy: Which
Way(s) Should be Followed ?Way(s) Should be Followed ?
Retrospective Cohorts
Prospective Cohorts
Passive Surveillance
Active Surveillance
Spontaneous Report
Specific HIV
populations
Non-specific HIV
populations
Proposed indicators for PVProposed indicators for PV Severe adverse events and their outcome/Number Severe adverse events and their outcome/Number
of patients on treatmentof patients on treatment
Number of of reporting centres for Number of of reporting centres for pharmacovigilance pharmacovigilance
Number of personnel trained to conduct Number of personnel trained to conduct pharmacovigilancepharmacovigilance
Number of reporting AE sites implementedNumber of reporting AE sites implemented
HIV Drug ResistanceHIV Drug Resistance
Cyril Pervilhac – SIR unit, HIV department
(input from S Bertagnolio, D Sutherland - SIR unit)
HIV Drug ResistanceHIV Drug Resistance
Rapid expansion of ART toward the goal of universal Rapid expansion of ART toward the goal of universal access - some level of HIV drug resistance (HIVDR) will access - some level of HIV drug resistance (HIVDR) will emerge (given lifelong treatment, HIV’s high mutation rate)emerge (given lifelong treatment, HIV’s high mutation rate)
Principles to minimize HIVDR emergence:Principles to minimize HIVDR emergence: appropriate drug prescribing and usageappropriate drug prescribing and usage assuring drug quality and uninterrupted drug suppliesassuring drug quality and uninterrupted drug supplies fostering access and adherencefostering access and adherence preventing HIV transmissionpreventing HIV transmission appropriate action based on standardized HIVDR appropriate action based on standardized HIVDR
monitoring and surveillancemonitoring and surveillance
The HIVDR 'essential package' The HIVDR 'essential package' for countries scaling up ARTfor countries scaling up ART
A.A. Development of a national HIVDR working Development of a national HIVDR working group and a national HIVDR plan/strategygroup and a national HIVDR plan/strategy
B.B. HIVDR Transmission SurveillanceHIVDR Transmission SurveillanceC.C. HIVDR Monitoring in ART Program sitesHIVDR Monitoring in ART Program sitesD.D. HIVDR Database DevelopmentHIVDR Database DevelopmentE.E. Development of a local WHO HIVDR support Development of a local WHO HIVDR support
Laboratory and nomination of the national or Laboratory and nomination of the national or regional WHO HIVDR genotyping testing labregional WHO HIVDR genotyping testing lab
Important indicators HIVDR Important indicators HIVDR strategy strategy
1)1) HIVDR Early Warning IndicatorsHIVDR Early Warning Indicators Survival at 6, 12, 24 months after treatment Survival at 6, 12, 24 months after treatment
initiationinitiation % pf patients on 1% pf patients on 1stst, 2, 2ndnd line regimen, 12 and line regimen, 12 and
24 months after treatment initiation24 months after treatment initiation
2)2) Direct HIVDR measuresDirect HIVDR measures Surveillance of HIVDR transmission Surveillance of HIVDR transmission Monitoring of HIVDR emergence in treatmentMonitoring of HIVDR emergence in treatment