Pre-departure HIV OrientationPre-departure HIV OrientationSession A: Pre-ART ConsiderationsSession A: Pre-ART Considerations

23 January, 200723 January, 2007

Royce C. Lin, MDAssistant Clinical Professor of MedicineUniversity of California, San FranciscoDirector, AIDS Consult ServiceSan Francisco General HospitalDeputy Director, ASPIREPositive Health Program, SFGH

GOALSGOALS

Overview: Pre-ART considerationsOverview: Pre-ART considerations

Medical indicationsMedical indications WHO guidelinesWHO guidelines Kenyan national guidelinesKenyan national guidelines US DHHS guidelinesUS DHHS guidelines WHO Staging systemWHO Staging system Cotrimoxazole prophylaxisCotrimoxazole prophylaxis Adherence issuesAdherence issues

Pre-ART considerations: USPre-ART considerations: US

Initial Visit

F/U Visit

HAART

F/U Visit

Full HPI, PMHFull Lab Counseling (tx, support)Establish relationshipAdjunct services (social, insurance)VaccinationsProblem list, Px, Rx

Follow CD4 declinePrep ART as CD4 <350

Choose regimen with pt inputAdherence counseling/support

Monitor toxicityTherapy switch as needed

Pre-ART considerations: RLSPre-ART considerations: RLS

Initial Visit

F/U visit

HAART

F/U Visit

HPI, PMH (form/algorithm driven)Select Labs (baseline + ?TB, preg)WHO staging (triage ART)Counseling (x 3. Peer groups support)Adjunct services (nutrition, HBC)CotrimoxazoleProblem list, Px, Rx (algorithm-driven)

See CD4 resultWith WHO, assess ART eligibilityAdherence counseling x 3 if ARTCotrimoxazole, other prevention

All get Triomune, unless contraindicationPregnancy? TB?

Monitor toxicity (TB, preg, IRIS)Therapy switch as needed

When to Start HAART?When to Start HAART?

All who have a CD4+ count ≤ 200 cells/mm3, regardless of stage of illness

All who are in WHO stage IV clinical criteria, regardless of CD4+ cell count

Consider those who are in WHO Stage III clinical criteria and have CD4 cell counts ≤ 350/mm3

Note! The patient must have expressed willingness and be ready to start therapy

When to Start Therapy in adultsKenyan Guidelines

U.S. DHHS Guidelines Summary: U.S. DHHS Guidelines Summary: ART recommended for…ART recommended for…

All with history of AIDS-defining All with history of AIDS-defining illness, regardless of CD4 countillness, regardless of CD4 count

All with CD4<200All with CD4<200 CD4 201-350 should be offered CD4 201-350 should be offered

therapytherapy CD4>350CD4>350

Most clinicians defer therapy regardless of Most clinicians defer therapy regardless of VLVL

Some offer therapy if VL>100,000Some offer therapy if VL>100,000

Perform WHO clinical staging

Confirmed HIV + Individual

WHO Clinical Stage 1

WHO Clinical Stage 2

WHO Clinical Stage 3

WHO Clinical Stage 4

Perform CD4+ T cell countEligible for ART regardless of CD4 count

CD4: <200 cells/mm3

Do NOT initiative ART. Monitor patient regularly

CD4: 200-350 cells/mm3

CD4: >350 cells/mm3

Eligible for ART regardless WHO Clinical stage

Consider ART ONLY if in WHO clinical stage III

WHO Clinical StagingWHO Clinical Staging

Natural History of Untreated HIV-1 Infection

Time in YearsInfection

CD4Cells

1000

800

600

400

200

0

Late Opportunistic Infections

+

1 2 3 4 5 6 7 8 9 10 11 12 13 14

CD4 < 100

Early OIs

CD4 Decline and WHO Staging

WHO 1

WHO 2

WHO 3

WHO 4

WHO Clinical Staging System for Adults and Adolescents

WHO Clinical Staging System for Adults and Adolescents

Stage I

Asymptomatic

Stage II

Not yet AIDS, but getting sick

CD4 usually 200-350

Courtesy of Jackie Dolev, M.D.Department of DermatologyUniversity of California, San Francisco

www.uptodate.com

www.uptodate.com

Prurigo

Herpes Zoster-Shingles

Stage III

Early AIDS

CD4 usually <200

Stage III

• Pulmonary TB

• Severe bacterial infections• Bacterial pneumonia• Pyomyositis

• Performance scale 3• Bedridden <50% in past month

Stage IV

Late AIDS

CD4 usually < 50-100

Other Stage IV

• Extrapulmonary TB• Cryptococcal Meningitis• Toxoplasmosis• Esophoegeal candidiasis• MAC• CMV Retinitis• HSV in mucocutaneous site• Progressive Multifocal Leukoencephalopathy• AIDS Dementia Complex• Weight loss >10% and bedbound >50%

PSYCHOSOCIALContraindications

OI Adherence?clinical

signs

Family andsupport?

CD4

MEDICALIndications

Substance abuse

Who should get ART first?Who should get ART first?

A. Female University StudentA. Female University Student CD4 178. Thrush. Treated with clotrimazoleCD4 178. Thrush. Treated with clotrimazole Family knows and is supportiveFamily knows and is supportive

B. Successful BusinessmanB. Successful Businessman CD4 168. Very high VL (>500,000)CD4 168. Very high VL (>500,000) Diagnosed 1 week, anxious, demands Diagnosed 1 week, anxious, demands

immediate ART. Reluctant to disclose to immediate ART. Reluctant to disclose to spouse.spouse.

C. Disbelieving Rural WomanC. Disbelieving Rural Woman CD4 47. Bacterial pneumonia. Cutaneous KSCD4 47. Bacterial pneumonia. Cutaneous KS Skeptical about her AIDS diagnosis.Skeptical about her AIDS diagnosis.

When to Start: PART IIWhen to Start: PART II

Medical consideration only half of the Medical consideration only half of the equationequation

Patient readiness EQUALLY importantPatient readiness EQUALLY important

Therapy quickly FAILS if suboptimal Therapy quickly FAILS if suboptimal adherenceadherence

>95% Adherence needed!>95% Adherence needed!

Especially important with Triomune!Especially important with Triomune!

Once first-line fails, second-line agents may Once first-line fails, second-line agents may not be effective and are more toxicnot be effective and are more toxic

BETTER TO WAIT AND START WHEN BETTER TO WAIT AND START WHEN PATIENT IS TRULY READYPATIENT IS TRULY READY

AdherenceAdherence

A major determinant of degree and A major determinant of degree and duration of viral suppressionduration of viral suppression

Poor adherence associated with Poor adherence associated with virologic failurevirologic failure

What percentage adherence is most What percentage adherence is most strongly-associated with emergence of strongly-associated with emergence of viral resistance?viral resistance?

Optimal suppression requires 90-Optimal suppression requires 90-95% adherence95% adherence

Even MORE important in resource-limited Even MORE important in resource-limited settings given lack of access to resistance settings given lack of access to resistance testing, limited salvage optionstesting, limited salvage options

Suboptimal adherence is commonSuboptimal adherence is common

Predictors of Inadequate AdherencePredictors of Inadequate Adherence

Poor clinician-patient relationshipPoor clinician-patient relationship

Active drug use or alcoholism Active drug use or alcoholism

Unstable housingUnstable housing

Mental illness (especially depression)Mental illness (especially depression)

Major life crisesMajor life crises

Lack of patient education Lack of patient education

Lack of patient access to medical care Lack of patient access to medical care

Medication adverse effectsMedication adverse effects

Fear of medication adverse effectsFear of medication adverse effects

Predictors of Good AdherencePredictors of Good Adherence

Emotional and practical supportsEmotional and practical supports Family, friends, social supportFamily, friends, social support

Importance of social work, CBOsImportance of social work, CBOs

Understanding the importance of adherenceUnderstanding the importance of adherence

Belief in efficacy of medicationsBelief in efficacy of medications

Keeping clinic appointmentsKeeping clinic appointments

Feeling comfortable taking medications in front Feeling comfortable taking medications in front

of othersof others

Convenience of regimenConvenience of regimen Consideration of patient preferences in Consideration of patient preferences in

constructing an antiretroviral regimenconstructing an antiretroviral regimen

Predictors of Inadequate AdherencePredictors of Inadequate Adherence

Age, race, sex, educational level, Age, race, sex, educational level, socioeconomic status, and a past history socioeconomic status, and a past history of alcoholism or drug use do of alcoholism or drug use do NOTNOT reliably reliably predict suboptimal adherence.predict suboptimal adherence.

Higher socioeconomic status and higher Higher socioeconomic status and higher education levels and lack of history of education levels and lack of history of drug use do drug use do NOTNOT reliably predict optimal reliably predict optimal adherence.adherence.

Practicum: Practicum: Case DiscussionsCase Discussions

Case scenario #1Case scenario #1

35 yo woman from Kisumu35 yo woman from Kisumu Tested HIV+ recentlyTested HIV+ recently

Comes to you for first visit in clinicComes to you for first visit in clinic Wants to know what she should doWants to know what she should do

Physically well, no symptomsPhysically well, no symptoms Baseline weight 68kg. Now 66kg.Baseline weight 68kg. Now 66kg.

What WHO clinical stage is she?What WHO clinical stage is she? What else do you want to know? What else do you want to know? What do you want to do today?What do you want to do today?

Case scenario #1Case scenario #1

1 year later, pt presents to casualty with 1 1 year later, pt presents to casualty with 1 month hx of dry, non-productive cough. month hx of dry, non-productive cough.

Hx: Increasing shortness of breathHx: Increasing shortness of breath Scant sputum. No hemoptysisScant sputum. No hemoptysis Weight: 59kg RR 32Weight: 59kg RR 32 CXR: diffuse, patchy bilateral infiltrates.CXR: diffuse, patchy bilateral infiltrates. Exam: Diffuse rales, L>R. Oral thrushExam: Diffuse rales, L>R. Oral thrush Pt is admitted to the wardPt is admitted to the ward

Has his clinical stage changed?Has his clinical stage changed? What stage do you guess him to be in now?What stage do you guess him to be in now?

What do you want to do now?What do you want to do now?

Case Scenario #1Case Scenario #1

Hospital courseHospital course Sputum x 3: smear negative for AFBSputum x 3: smear negative for AFB Started empirically on amoxicillin without Started empirically on amoxicillin without

improvement.improvement. TMP/SMX begun (for presumed PCP)TMP/SMX begun (for presumed PCP) 5-days later: decreased SOB, cough5-days later: decreased SOB, cough Discharged. Complete Rx at homeDischarged. Complete Rx at home

5 days later (day#10 rx)5 days later (day#10 rx) Seen in clinicSeen in clinic Still on PCP treatment. Finished amoxicillinStill on PCP treatment. Finished amoxicillin CD4 comes back: 178CD4 comes back: 178 Feeling much better, slight residual coughFeeling much better, slight residual cough Weight 57kg. RR 18. Rales resolved.Weight 57kg. RR 18. Rales resolved.

When do you want to start ART?When do you want to start ART?

Case Scenario #1Case Scenario #1

Who wants to start ART today?Who wants to start ART today? Does he meet medical indications to start ART?Does he meet medical indications to start ART?

By which criteria?By which criteria?

What are other considerations?What are other considerations? What would you do at this visit?What would you do at this visit? When is the optimal time to start ART?When is the optimal time to start ART?

Teaching pointsTeaching points

Wait until OI is treatedWait until OI is treated Increased overlapping toxicityIncreased overlapping toxicity

Increased risk of immune reconstitution syndromeIncreased risk of immune reconstitution syndrome

Prepare patient for ARTPrepare patient for ART Assess psychosocial readinessAssess psychosocial readiness

Establish relationshipEstablish relationship

Involve entire care teamInvolve entire care team

Good preparation = Successful therapyGood preparation = Successful therapy

SummarySummary

Medical IndicationsMedical Indications Any AIDS-defining conditionAny AIDS-defining condition

Any OIAny OI WHO Stage IVWHO Stage IV

CD4<200CD4<200 WHO, US guidelines agreeWHO, US guidelines agree

Psychosocial contraindicationsPsychosocial contraindications Factors of adherenceFactors of adherence Belief systemsBelief systems Role of social work, CBO, supportRole of social work, CBO, support

Balance between the two determines when Balance between the two determines when to start ARTto start ART

Careful consideration of both sides of equation leads to Careful consideration of both sides of equation leads to optimal chance at successful suppression of HIV.optimal chance at successful suppression of HIV.