Preparing for HAART Cyril Goshima, M. D. Monday April 4, 2005.

Preparing for HAARTPreparing for HAART

Cyril Goshima, M. D.Cyril Goshima, M. D.

MondayMonday

April 4, 2005April 4, 2005

Prior to Considering HAART for Prior to Considering HAART for Your CommunitiesYour Communities

HIV Testing with Confirmatory Tests must HIV Testing with Confirmatory Tests must be available.be available.

Certain Minimal Tests must be available Certain Minimal Tests must be available e.g. CBCe.g. CBC

At least two Classes of Antiviral At least two Classes of Antiviral Medications must be available on an Medications must be available on an ongoing basis.ongoing basis.

Providers trained in HIV CareProviders trained in HIV Care

Indications for ARTIndications for ART

World Health OrganizationWorld Health Organization DHHS GuidelinesDHHS Guidelines IAS-USA GuidelinesIAS-USA Guidelines

WHO Staging System for HIV WHO Staging System for HIV Infection & Disease in Adults & Infection & Disease in Adults &

AdolAdolescentsescents Clinical Stage IClinical Stage I

AsymptomaticAsymptomatic Generalized LymphadenopathyGeneralized Lymphadenopathy

Clinical Stage IIClinical Stage II Wt. loss <10%of BWWt. loss <10%of BW Minor mucocutaneous manifestations e.g. Minor mucocutaneous manifestations e.g.

onychomycosis, seb. derm., prurigo, angular cheilitisonychomycosis, seb. derm., prurigo, angular cheilitis Herpes Zoster within the last 5 yrs.Herpes Zoster within the last 5 yrs. Recurrent URI e.g. bacterial sinusitisRecurrent URI e.g. bacterial sinusitis And/or performance scale 2: symptomatic, normal And/or performance scale 2: symptomatic, normal

activityactivity

WHO Staging SystemWHO Staging System

Clinical Stage IIIClinical Stage III Wt. loss > 10% of BWWt. loss > 10% of BW Unexplained chronic diarrhea > 1 mo.Unexplained chronic diarrhea > 1 mo. Unexplained prolonged fever (intermittent or chronic) Unexplained prolonged fever (intermittent or chronic)

> 1 mo.> 1 mo. Oral CandidiasisOral Candidiasis Oral Hairy LeucoplakiaOral Hairy Leucoplakia Pulmonary TBPulmonary TB Severe Bacterial infections e.g. pneumoniaSevere Bacterial infections e.g. pneumonia And/or performance scale 3: bedridden < 50 % of the And/or performance scale 3: bedridden < 50 % of the

day during last monthday during last month

WHO Staging SystemWHO Staging System

Clinical Stage IVClinical Stage IV HIV Wasting SyndromeHIV Wasting Syndrome Opportunistic InfectionsOpportunistic Infections Any disseminated endemic mycosisAny disseminated endemic mycosis Non-typhoid Salmonella SepticemiaNon-typhoid Salmonella Septicemia Extra-pulmonary TBExtra-pulmonary TB LymphomaLymphoma Kaposi’s SarcomaKaposi’s Sarcoma HIV encephalopathyHIV encephalopathy And/or performance scale 4: bedridden > 50% of the And/or performance scale 4: bedridden > 50% of the

day during last mo.day during last mo.

WHO Recommendations for WHO Recommendations for Starting ART in Adults and Starting ART in Adults and

AdolescentsAdolescents

Documented HIV InfectionDocumented HIV Infection If CD4 testing is availableIf CD4 testing is available

WHO Stage IV disease, irrespective of CD4WHO Stage IV disease, irrespective of CD4 WHO Stage III disease, CD4 < 350WHO Stage III disease, CD4 < 350 WHO Stage I or II disease, CD4 < or = 200WHO Stage I or II disease, CD4 < or = 200

WHO Recommendations for WHO Recommendations for Starting ART in Adults & Starting ART in Adults &

AdolescentsAdolescents

CD4 Testing UnavailableCD4 Testing Unavailable WHO Stage IV disease, irrespective of TLCWHO Stage IV disease, irrespective of TLC WHO Stage III disease, irrespective of TLCWHO Stage III disease, irrespective of TLC WHO Stage II disease with TLC < or = 1200WHO Stage II disease with TLC < or = 1200 WHO Stage I, ART not recommendedWHO Stage I, ART not recommended

Viral Load is considered not necessaryViral Load is considered not necessary TLC is a useful marker of prognosis & TLC is a useful marker of prognosis &

survival in combination with clinical stagingsurvival in combination with clinical staging

DHHS Guidelines for Initiating ART DHHS Guidelines for Initiating ART in Adults and Adolescentsin Adults and Adolescents

Clinical Clinical CD4 CountCD4 Count Viral LoadViral Load Recomm.Recomm.

Sym./AIDSSym./AIDS AnyAny AnyAny TreatTreat

Asymp./Asymp./

AIDSAIDS

<200<200 AnyAny TreatTreat

Asymp.Asymp. >200, <350>200, <350 AnyAny Offer esp.Offer esp.

VL >20KVL >20K

Asymp.Asymp. >350>350 >100K>100K ConsiderConsider

Asymp.Asymp. >350>350 <100K<100K DeferDefer

DHHS Guidelines for Initiating ART DHHS Guidelines for Initiating ART in Adults & Adolescentsin Adults & Adolescents

Guidelines for initiating ART in pregnant women Guidelines for initiating ART in pregnant women are different depending on the stage of are different depending on the stage of pregnancy.pregnancy.

If a pregnant woman needs ART for her health If a pregnant woman needs ART for her health then, ART should be started irregardless of the then, ART should be started irregardless of the trimester. EFV should be avoided and NVP trimester. EFV should be avoided and NVP should be used with caution or avoided in should be used with caution or avoided in women with CD4 >250.women with CD4 >250.

Delaying ART until after 10-12 wks. gestation. Delaying ART until after 10-12 wks. gestation.

IAS-USA Guidelines-2004 for IAS-USA Guidelines-2004 for Initiating ART in Adults/Adoles.Initiating ART in Adults/Adoles.

ClinicalClinical CD4CD4 Viral LoadViral Load Recomm.Recomm.

Symp./Symp./

AIDSAIDS

AnyAny AnyAny TreatTreat

<200<200 AnyAny TreatTreat

200-350200-350 >50K, *>50K, * ConsiderConsider

350-500350-500 >100K, *>100K, * ConsiderConsider

>500>500 MonitorMonitor

IAS-USA Guidelines 2004IAS-USA Guidelines 2004Initiating TherapyInitiating Therapy

* other criteria for considering therapy is a * other criteria for considering therapy is a more rapid decline in CD4 by 100 in a yearmore rapid decline in CD4 by 100 in a year

Comparison of the Guidelines for Comparison of the Guidelines for Initiating ARTInitiating ART

Clinical staging importantClinical staging important Severe symptoms or AIDS Defining Severe symptoms or AIDS Defining

Conditions Conditions Evidence of significant immunological Evidence of significant immunological

suppressionsuppression CD4 cut off around 350CD4 cut off around 350

Considerations for the pregnant womenConsiderations for the pregnant women Timing, medications to be avoidedTiming, medications to be avoided

Initial ART RegimensInitial ART Regimens

WHO for Resource Limited SettingsWHO for Resource Limited Settings Usage in Pregnancy: NVP+3TC+d4T or AZT, Usage in Pregnancy: NVP+3TC+d4T or AZT,

avoid EFVavoid EFV Usage with TB Co-Infection: EFV+3TC+d4T Usage with TB Co-Infection: EFV+3TC+d4T

or AZT, avoid NVP with incr. LFTor AZT, avoid NVP with incr. LFT AZT use more costly with the addition of Hct AZT use more costly with the addition of Hct

monitoring.monitoring. NVP+3TC+d4T and NVP+3TC+AZT available NVP+3TC+d4T and NVP+3TC+AZT available

in fixed dose combinationin fixed dose combination

Initial ARTInitial ART

DHHS Guidelines – 2004DHHS Guidelines – 2004 Preferred NNRTI-Based Regimens:Preferred NNRTI-Based Regimens:

• EFV+(3TC or FTC)+(AZT or TDF), except in EFV+(3TC or FTC)+(AZT or TDF), except in pregnant women or women with pregnancy pregnant women or women with pregnancy potentialpotential

• 3TC+AZT is in a fixed combination pill, Epzicom3TC+AZT is in a fixed combination pill, Epzicom• FTC+TDF is in a fixed combination pill, Truvada FTC+TDF is in a fixed combination pill, Truvada

Preferred PI-Based Regimens:Preferred PI-Based Regimens:• LPVr+(3TC or FTC)+AZTLPVr+(3TC or FTC)+AZT

Initial ARTInitial ART

DHHS Guidelines – 2004 cont’dDHHS Guidelines – 2004 cont’d Alternative NNRTI-Based Regimens:Alternative NNRTI-Based Regimens:

• EFV+(3TC or FTC)+other NRTIEFV+(3TC or FTC)+other NRTI• NVP+(3TC or FTC)+other NRTINVP+(3TC or FTC)+other NRTI

Alternative PI-Based Regimens:Alternative PI-Based Regimens:• Other PI+(3TC or FTC)+other NRTIOther PI+(3TC or FTC)+other NRTI• Many PI are boosted with RTV, except NFVMany PI are boosted with RTV, except NFV

Initial ARTInitial ART

IAS-USA Guidelines – 2004IAS-USA Guidelines – 2004 NNRTI Component:NNRTI Component:

• EFV, NVP for selected pts.EFV, NVP for selected pts.• NNRTI Component to be used with NRTI componentNNRTI Component to be used with NRTI component

PI ComponentPI Component• ATZr, SQVr, LPVr, IDVr (r=boosted with RTV)ATZr, SQVr, LPVr, IDVr (r=boosted with RTV)• PI Component to be used with NRTI ComponentPI Component to be used with NRTI Component

NRTI Component:NRTI Component:• (AZT or TDF)+(3TC or FTC)(AZT or TDF)+(3TC or FTC)• ddI+FTCddI+FTC

Initial ARTInitial ART

IAS-USA Guidelines – 2004IAS-USA Guidelines – 2004 Alternative PI Components: FAPr, ATZ, NFVAlternative PI Components: FAPr, ATZ, NFV Alternative NRTI Components: ABC+3TC, Alternative NRTI Components: ABC+3TC,

ddI+3TC, AZT+ABC, d4T+3TCddI+3TC, AZT+ABC, d4T+3TC Both DHHS and IAS-USA Guidelines list Both DHHS and IAS-USA Guidelines list

AZT+3TC+ABC in a fixed combination as AZT+3TC+ABC in a fixed combination as an alternative in special circumstancesan alternative in special circumstances

Regimens or Components of ART Regimens or Components of ART That Are Not RecommendedThat Are Not Recommended

MonotherapyMonotherapy Two-Agent Drug CombinationsTwo-Agent Drug Combinations TDF+3TC+ABC or TDF+3TC+ddITDF+3TC+ABC or TDF+3TC+ddI AZT+3TC+ABC (Trizivir)AZT+3TC+ABC (Trizivir) ATV+IDV (hyperbilirubinemia)ATV+IDV (hyperbilirubinemia) AZT+d4T (antagonistic)AZT+d4T (antagonistic) Combination of “d” drugsCombination of “d” drugs

Regimens or Components of ART Regimens or Components of ART That Are Not Recommended That Are Not Recommended

EFV in Pregnancy (teratogenic in non-EFV in Pregnancy (teratogenic in non-human primates)human primates)

d4T+ddI in Pregnancy (lactic acidosis)d4T+ddI in Pregnancy (lactic acidosis) FTC+3TC (no benefit)FTC+3TC (no benefit) 2 NNRTI (increase in side effects)2 NNRTI (increase in side effects)

AdherenceAdherence

Adherence is the most important factor in Adherence is the most important factor in the success of ART.the success of ART.

Barriers to achieving adherence:Barriers to achieving adherence: Readiness to beginning treatmentReadiness to beginning treatment Pill “burden”Pill “burden” Side EffectsSide Effects Dosing Schedule, Storage & Food Dosing Schedule, Storage & Food

RequirementsRequirements

AdherenceAdherence

Barriers to Achieving Adherence:Barriers to Achieving Adherence: Co-Morbid Conditions e.g. TB, Hepatitis, Co-Morbid Conditions e.g. TB, Hepatitis,

Mental Illness, Active Substance Use Mental Illness, Active Substance Use Specific Cultural IssuesSpecific Cultural Issues Lack of Family, Community, Country SupportLack of Family, Community, Country Support

When to Change TherapyWhen to Change Therapy

Clinical Failure: HIV-related event 3 or more Clinical Failure: HIV-related event 3 or more months after start of ART excluding months after start of ART excluding reconstitution syndromes. WHO: Stg. III, IV.reconstitution syndromes. WHO: Stg. III, IV.

Immunologic Failure: Failure to increase CD4 Immunologic Failure: Failure to increase CD4 25-50 cells during the first year of ART. WHO: 25-50 cells during the first year of ART. WHO: return to pre-treatment baseline or fall >50%.return to pre-treatment baseline or fall >50%.

Virologic Failure: Failure to achieve VL <400 by Virologic Failure: Failure to achieve VL <400 by 24 wks. or <50 by 48 wks.24 wks. or <50 by 48 wks.

Criteria for children are different.Criteria for children are different.

What to Change to?What to Change to?

Change at least 2 and at best all 3 ARV.Change at least 2 and at best all 3 ARV. Try to avoid the use of 3 classes of ARV Try to avoid the use of 3 classes of ARV

together, i.e. NRTI + NNRTI + PI.together, i.e. NRTI + NNRTI + PI. Dual PI therapy is an option.Dual PI therapy is an option. Mega-HAART: whatever the patient can Mega-HAART: whatever the patient can

tolerate.tolerate. Better to be on ART than not.Better to be on ART than not.

What to Change to?What to Change to?

Special Considerations:Special Considerations: Women of child bearing ageWomen of child bearing age Pts. on TB therapyPts. on TB therapy Hepatitis B Co-Infection: hepatitis flare if stop Hepatitis B Co-Infection: hepatitis flare if stop

3TC, FTC, TDF3TC, FTC, TDF Resistance TestingResistance Testing

Where availableWhere available

Any Questions?Any Questions?