Session B: HIV AntiretroviralsSession B: HIV Antiretrovirals

Pre-departure OrientationPre-departure Orientation

23 January 200723 January 2007

Royce C. Lin, MDAssistant Clinical Professor of MedicineUniversity of California, San FranciscoDirector, AIDS Consult ServiceDeputy Director, ASPIREPositive Health Program. HIV/AIDS DivisionSan Francisco General Hospital

GOALSGOALS

Review Kenyan ART guidelinesReview Kenyan ART guidelines Discuss WHO 2006 guidelines Discuss WHO 2006 guidelines Review individual ARV agentsReview individual ARV agents

ToxicityToxicity Side effectsSide effects Monitoring considerationsMonitoring considerations

Review principles of therapy switchReview principles of therapy switch For side effectsFor side effects For adverse eventsFor adverse events

Case StudiesCase Studies

Available ANTIRETROVIRALS: U.S.

NRTI (nucleoside analogs)• Abacavir ABC• Didanosine DDI• Emtricitabine FTC• Lamivudine 3TC• Stavudine D4T• Zidovudine ZDV• Zalcitabine DDC• Tenofovir TDF

NNRTI (non-nucleosides)• Delavirdine DLV• Efavirenz EFV• Nevirapine NVP

Protease Inhibitor• Amprenavir APV• Atazanavir ATV• Fosamprenavir FPV• Indinavir IDV• Lopinavir LPV• Nelfinavir NFV• Ritonavir RTV• Saquinavir SQV• Darunavir TMC-114

Fusion Inhibitor• Enfuvirtide T-20

Integrase Inhibitors

Selecting HAART regimen: USSelecting HAART regimen: US

Full access to all antiretroviral agentsFull access to all antiretroviral agents Which specific combo depends onWhich specific combo depends on

Existing comorbidities, lab abnormalitiesExisting comorbidities, lab abnormalities Genotype (transmitted resistance)Genotype (transmitted resistance) Patient preferencesPatient preferences Once-daily dosing; pill burden considerationsOnce-daily dosing; pill burden considerations Wide variation in combos prescribedWide variation in combos prescribed Benefits: tailor-fit; option to switchBenefits: tailor-fit; option to switch

Selecting HAART regimen: RLSSelecting HAART regimen: RLS

Limited access to all antiretroviral agentsLimited access to all antiretroviral agents Generally, one-size-fits all:Generally, one-size-fits all:

Cheap generics make ART ‘roll-out’ possibleCheap generics make ART ‘roll-out’ possible Algothrithmic approach enable rapid scale-upAlgothrithmic approach enable rapid scale-up But this results in limited options, essentially….But this results in limited options, essentially….

Triomune for allTriomune for all, unless:, unless: Contraindication to any componentContraindication to any component Treatment of active TBTreatment of active TB Pregnancy considerationsPregnancy considerations Treatment-limiting SAE/toxicityTreatment-limiting SAE/toxicity

Constructing an Constructing an Antiretroviral Regimen for Antiretroviral Regimen for Initial Therapy: Initial Therapy:

a US-based approacha US-based approach

Royce C. Lin, MDAssistant Clinical Professor

Constructing a HIV Constructing a HIV Antiretroviral Antiretroviral

regimenregimen Key principle: 3 Key principle: 3 activeactive drugs drugs 2 NRTI + NNRTI or PI2 NRTI + NNRTI or PI

““Nuc” backbone + Nuc” backbone + eithereither PI or NNRTI PI or NNRTI AKA: Two scoops rice + chicken or beefAKA: Two scoops rice + chicken or beef Choosing a regimenChoosing a regimen

Step 1: Decide: NNRTI or PIStep 1: Decide: NNRTI or PI Step 2: Pick a NRTI ”backbone”Step 2: Pick a NRTI ”backbone” Choose components based on toxicityChoose components based on toxicity Take into account side effect, pill burden, Take into account side effect, pill burden,

patient preference, and costpatient preference, and cost

Guidelines for the Use of Antiretrovirals in HIV-1 infected Adults and Adolescents10 October 2006, Department of Health and Human Services, USA

Summary: DHHS Guidelines 2006

Two ScoopsChicken Beef

Antiretroviral Therapy for HIV Infection in Adults and Adolescents in Resource-limited Settings: Toward Universal Access. World Health Organisation 2006 Revision.

WHO 2006 Guidelines: Summary Table

Antiretroviral Therapy for HIV Infection in Adults and Adolescents in Resource-limited Settings: Toward Universal Access. World Health Organisation 2006 Revision.

WHO 2006 Guidelines: Summary Table

Majority: D4T + 3TC + NVP in FDC

Recommended first-line regimens in TZ

I d4T+3TC+NVP, (All in one tablet: Fixed Dose Combination (FDC):

Triomune 40 twice daily (> 60 kg body weight).

Triomune 30 twice daily (< 60 kg body weight).

NB: For new patients use Nevirapine only once a day (half dose) for first 2 weeks by giving 1triomune in the

evening and d4t and 3TC separate tablets in the morning

II AZT+3TC+NVP

Zidovudine and Lamivudine and Nevirapine, each twice daily

NB: For new patients use Nevirapine only once a day (half dose) for first 2 weeks

Recommended first-line regimens in TZ, continued

III d4T+3TC+EFV

Stavudine and Lamivudine twice daily and Efavirenz 600 mg once daily at night

IV AZT+3TC+EFV

Zidovudine and Lamivudine twice daily and Efavirenz once daily at night.

Indications to change antiretroviral therapy within first line regime are to be determined by prescribing doctor: (see next slide)

Recommended second-line regimens in Kenya

ABC + ddI + LPV/r

Abacavir and Lopinavir/ritonavir two times a day and Didanosine once a day on empty stomach

ABC + TDF + LPV/r

Learning ARVs for KenyaLearning ARVs for Kenya

GoalsGoals

Monitoring for Monitoring for SAFETYSAFETY ARVs have many toxicitiesARVs have many toxicities Toxicity depend on ARV classToxicity depend on ARV class Some ARVs have fatal toxicitiesSome ARVs have fatal toxicities

Switching therapySwitching therapy Some clients cannot tolerate their ART regimenSome clients cannot tolerate their ART regimen

Side effectsSide effects ToxicityToxicity FailureFailure

Knowing how a HIV regimen is put together allows Knowing how a HIV regimen is put together allows you to make intelligent and safe changes.you to make intelligent and safe changes.

How to learn ARVSHow to learn ARVS

Divide individual ARVs into 3 classesDivide individual ARVs into 3 classes NRTINRTI NNRTINNRTI PIPI

Learn the “class effects”Learn the “class effects” Each class of ARVs have common toxicitiesEach class of ARVs have common toxicities

If you can remember which class an ARV belongs If you can remember which class an ARV belongs to, you can remember which toxicities to watch to, you can remember which toxicities to watch forfor

Learn individual drugsLearn individual drugs Learn any other unique properties of each drug.Learn any other unique properties of each drug.

Knowing each drug Knowing each drug wellwell is one of the most is one of the most important parts of being a good HIV care and important parts of being a good HIV care and treatment provider!treatment provider!

NRTI

Nucleoside/tide Reverse Transcriptase Inhibitors

(mimics Adenosine, Thymidine, Guanine, or Cytosine)

NRTI: class effects

• All may cause:– Mitochondrial toxicity– Lactic acidosis– Pancreatitis– Peripheral Neuropathy– Lipodystrophy – Hepatotoxicity

NRTI tipsNRTI tips

How to recognize a NRTIHow to recognize a NRTI 3 letters or numbers3 letters or numbers

AZT, 3TC, DDI, D4T, ABC, TDFAZT, 3TC, DDI, D4T, ABC, TDF Generic name usually end in “ine”Generic name usually end in “ine”

Zidovudine, lamividine, didanosine, stavudineZidovudine, lamividine, didanosine, stavudine NRTI Exceptions: abacavir, tenofovir end in “vir” but are NRTI Exceptions: abacavir, tenofovir end in “vir” but are

NRTIsNRTIs NNRTI Exceptions: nevirapine, delavirdine are NNRTI but NNRTI Exceptions: nevirapine, delavirdine are NNRTI but

end in “ine”end in “ine” NRTI = “Backbone” of ARTNRTI = “Backbone” of ART

FoundationFoundation of most ART combinations of most ART combinations ““Two scoops of rice” plus chicken or beefTwo scoops of rice” plus chicken or beef Two NRTI (rice) PLUSTwo NRTI (rice) PLUS

Chicken (NNRTI) orChicken (NNRTI) or Beef (PI)Beef (PI)

NRTIsNRTIs

Essential part of any Essential part of any ART combinationART combination

Less drug-drug Less drug-drug interactionsinteractions

Availability in resource-Availability in resource-limited settingslimited settings

Individual drugs with Individual drugs with unique side unique side effects/toxicitieseffects/toxicities

Class effect: Class effect: Lactic acidosisLactic acidosis Mitochondrial toxicityMitochondrial toxicity Peripheral neuropathyPeripheral neuropathy LipodystrophyLipodystrophy HepatotoxicityHepatotoxicity

ADVANTAGES DISADVANTAGES

3TC (lamivudine/Epivir)

• Toxicity– Few– Hepatitis B exacerbation

• Side Effects– Few; class effect

• Dosing– 150mg bid or– 300mg qd– Renal dosing available

• Special Considerations

– Hepatitis B

D4T (stavudine/Zerit)

• Toxicity– Lipoatrophy– Peripheral neuropathy– Pancreatitis– Lactic acidosis

• Side Effects– Gen well-tolerated

• Dosing– 40mg bid (if >60kg)– 30mg bid (if <60kg)

Malar Wasting of Lipoatrophy

AZT (zidovudine/Retrovir)

• Toxicity– Anemia– Neutropenia– Thrombocytopenia– Myopathy

• Side Effects– Nausea/vomiting– Headache– Dizziness

• Dosing– 300mg bid

DDI (didanosine/Videx)

• Toxicity– Lactic acidosis– Peripheral neuropathy– Pancreatitis– Lipodystrophy

• Side Effects– GI

• Dosing– If EC, 400mg QD (<60kg:

250mg qd)– If reg tabs, 200mg bid

(<60kg:125 bid/250qd)

– Empty stomach

ABC (abacavir/Ziagen)• Toxicity

– FATAL hypersensitivity• Rash• Fever• GI (nausea/vomiting)• Respiratory (SOB)• Hypotension

• Death on re-challenge– Class effect

• Side Effects– Nausea, other GI

• Dosing– 300mg bid or 600mg qd– Co-formulated with 3TC as Epzicom

TDF (tenofovir/Viread)

• Toxicity– Renal failure

• Renal Tubular Necrosis• Hypophosphatemia

– Hepatitis B exacerbation• Side Effects

– Gen well-tolerated• Dosing

– 300mg QD– Avoid in borderline renal

dysfunction– Fanconi’s syndrome (rare)– Renal dosing necessary

• Special Considerations– Hepatitis B

NNRTI

NON-nucleoside Reverse Transcriptase Inhibitors

(blocks RT directly, NOT a nucleoside-analogue)

NNRTI: class effects

• All may cause:

– Rash

– Hepatotoxicity

NNRTIsNNRTIs

Ease (low pill burden)Ease (low pill burden) TolerabilityTolerability Less metabolic effectsLess metabolic effects

fat maldistribution, fat maldistribution, dyslipidemiadyslipidemia

Availability in resource-Availability in resource-limited settingslimited settings

Prone to resistance Prone to resistance single mutationsingle mutation Cross resistance among Cross resistance among

NNRTIsNNRTIs Rash; hepatotoxicityRash; hepatotoxicity Potential drug Potential drug

interactions (CYP450)interactions (CYP450)

ADVANTAGES DISADVANTAGES

NVP (nevirapine/Viramune)• Toxicity

– Hepatotoxicity (can be fatal)• Cases of fulminant hepatitis

death• Usually within 6 wks• Not in PMTCT• Increased risk in women

– 12-fold risk: women, CD4>250– 4-fold risk: men, CD4>400

– Rash (can be fatal)• Stevens-Johnson (erythema

multiforme major)• Toxic epidermal necrolysis• Mild rash COMMON

• Side Effects• Well-tolerated

• Dosing• Lead-in dosing: 200mg daily x 2

weeks, then 200mg bd

EFV (efavirenz/Sustiva)

• Toxicity– Rash– Hepatitis– Teratogenic

• Not for use in women of childbearing potential

• Side Effects– CNS

• Insomnia/Somnolence• Vivid dreams• “Spacey”, poor

concentration• Gen. ↓ after 1-2 wks

• Dosing– 600 mg qd

P I

Protease Inhibitors

(binds/disables viral protease enzyme)

PI: class effects

• All may cause:

– Hyperlipidemia

– Hyperglycemia

– Fat redistribution

– CYP 3A4 inhibitors

– multiple drug-drug interactions

Protease InhibitorsProtease Inhibitors

High potencyHigh potency Longest prospective Longest prospective

data (durability)data (durability) Esp. in advanced Esp. in advanced

AIDSAIDS Less susceptible to Less susceptible to

resistance from virusresistance from virus ““Salvage” therapy Salvage” therapy

when NNRTI fails when NNRTI fails

Metabolic complications Metabolic complications fat maldistribution, fat maldistribution,

dyslipidemia, dyslipidemia, insulin resistanceinsulin resistance

Drug interactions Drug interactions (CYP3A4)(CYP3A4)

High costHigh cost Limited availability Limited availability

ADVANTAGES DISADVANTAGES

Ritonavir (RIT/Norvir)

• Toxicity• Hepatotoxicity• Hyperlipidemia• Hyperglycemia/ insulin

resistance• Drug-drug interactions!• Potent inhibition CYP3A4• Increases levels of other PIs• Must check interactions

• Side Effects– GI

• Nausea/vomiting• Diarrhea• Abdominal pain

• Dosing• “boosting” 100-200mg qd

KAL (lopinavir+rit/Kaletra)

• Toxicity• Hyperlipidemia• Hyperglycemia/ insulin

resistance• Drug-drug interactions

• Side Effects– GI

• Nausea/vomiting• Diarrhea• Abdominal pain

• Dosing• 3 tabs bid (400/100mg)

• Other• Most potent ARV• Hard to develop resistance

(>5 major PI-associated mutations ↓ efficacy)

Constructing a HIV Constructing a HIV Antiretroviral regimenAntiretroviral regimen

2 NRTI + NNRTI or PI2 NRTI + NNRTI or PI Exception: 3 NRTI in special Exception: 3 NRTI in special

circumstances onlycircumstances only

Choose components based on toxicityChoose components based on toxicity

Take into account side effect, pill burden, Take into account side effect, pill burden, patient preference, and costpatient preference, and cost

Always need 3 active drugs!Always need 3 active drugs!

3TC(or FTC)

+

AZT

D4T(or DDI)

ABC

TDF

NRTI Backbone

AVOID

+

+

D4T AZT

Competitive InhibitionLevels ↓

D4T

ddI

ddC

Excessivetoxicity

Putting it all togetherPutting it all togetherCases in Treatment with ARTCases in Treatment with ART

I. d4T + 3TC + NVP

III. d4T + 3TC + EFV IV. AZT + 3TC + EFVII. AZT + 3TC + NVP

Replace NVP with EFV due to:• Hepatoxicity• NVP intolerance• TB patient on rifampicin

Replace d4T with AZT due to:• Peripheral neuropathy and NO anaemia

Replace NVP with EFV due to:• Hepatoxicity• NVP intolerance• TB patient

Replace d4T with AZT due to:

• Peripheral neuropathy and NO anaemia

Modified 1st line regimen

1st line regimen

Algorithm for selecting first line treatment

Case 1: Switching for complicationsCase 1: Switching for complications

34 yo Kenyan woman34 yo Kenyan woman WHO IV, CD4 45WHO IV, CD4 45 HIV wasting, chronic diarrheaHIV wasting, chronic diarrhea Exam: cachexia, conjunctival pallorExam: cachexia, conjunctival pallor Labs: Labs:

HgB 7HgB 7 WBC 1.2 WBC 1.2

(40% PMN, 59% lymph, 1% eos)(40% PMN, 59% lymph, 1% eos) Plt 140kPlt 140k Remaining normalRemaining normal

OK to start Kenyan first-line therapy?OK to start Kenyan first-line therapy? What if you are in South Africa?What if you are in South Africa?

First-line is efavirenz/3TC/AZTFirst-line is efavirenz/3TC/AZT

Case 2: Switching for ComplicationsCase 2: Switching for Complications

45 yo man45 yo man WHO III, CD4 170WHO III, CD4 170 Prurigo, onychomycosis, and oral Prurigo, onychomycosis, and oral

hairy leukoplakia and treated thrushhairy leukoplakia and treated thrush Pre-ART labs: all normalPre-ART labs: all normal Started on TriomuneStarted on Triomune

4-months later, hospitalized for 4-months later, hospitalized for severe abdominal pain, nausea, severe abdominal pain, nausea, vomiting, dehydration, inability to vomiting, dehydration, inability to tolerate oral solids/liquidstolerate oral solids/liquids

Differential diagnosis?Differential diagnosis? What is your work-up?What is your work-up?

Case 2Case 2

Hospital labs:Hospital labs: CBC, chemistry, LFT nlCBC, chemistry, LFT nl Lipase 600Lipase 600

Clinical course:Clinical course: ART stoppedART stopped Hydration, electrolyte supportHydration, electrolyte support Discharged 3 days laterDischarged 3 days later

When the patient returns, would you When the patient returns, would you resume ART? If so, with what combination?resume ART? If so, with what combination?

Case 3Case 3 45 yo Ugandan woman 45 yo Ugandan woman In 2002 ago was WHO IIIIn 2002 ago was WHO III

Weight loss (75kg Weight loss (75kg 66kg) 66kg) Recurrent thrush, vaginal candidiasisRecurrent thrush, vaginal candidiasis Zoster with post-herpetic neuralgiaZoster with post-herpetic neuralgia

Social: administrative assistantSocial: administrative assistant Limited income, can spend up to 25,000 TSH on Limited income, can spend up to 25,000 TSH on

medicationsmedications Advised to purchase generic TriomuneAdvised to purchase generic Triomune

Started Triomune October 2002Started Triomune October 2002 4 months later, weight 66kg 4 months later, weight 66kg 70kg 70kg 8 months later, no more recurrence of 8 months later, no more recurrence of

thrush thrush 1 yr later, weight 74kg1 yr later, weight 74kg 3 yrs later, weight 74 kg3 yrs later, weight 74 kg

Complains “I am starting to like a man….I think I look Complains “I am starting to like a man….I think I look strange in the face”strange in the face”

Fat loss in thighs and face.Fat loss in thighs and face. Otherwise feels well.Otherwise feels well.

Case 7: Switching for complicationsCase 7: Switching for complications

33 yo Tanzanian woman33 yo Tanzanian woman Spouse also HIV+Spouse also HIV+ WHO Stage III, CD4 180WHO Stage III, CD4 180 Sexually active, cannot afford Sexually active, cannot afford

condomscondoms Complains of chronic cough for 2 Complains of chronic cough for 2

monthsmonths Exam: thrushExam: thrush Labs: all within normal parametersLabs: all within normal parameters CXR: “clear”CXR: “clear” OK to start Triomune?OK to start Triomune?

Case 7Case 7

Started on TriomuneStarted on Triomune Tolerated well, no problemsTolerated well, no problems 3 weeks later3 weeks later

Cough increasedCough increased FeverFever Weight lossWeight loss

Differential diagnosis?Differential diagnosis? Exam: Exam:

Rales in RLL and LULRales in RLL and LUL CXR: R apical infiltrate and LLL diffuse opacity, hilar CXR: R apical infiltrate and LLL diffuse opacity, hilar

lymphadenopathy not seen on prior CXRlymphadenopathy not seen on prior CXR Labs: WNLLabs: WNL

Course of Action?Course of Action?

Case 7Case 7

DiagnosticsDiagnostics Sputum for AFBSputum for AFB Given AmoxicillinGiven Amoxicillin

No improvementNo improvement AFB smear+AFB smear+

What should you do now?What should you do now? Start anti-TB therapy?Start anti-TB therapy? Continue Triomune?Continue Triomune? Stop Triomune?Stop Triomune? Replace Triomune?Replace Triomune?

Drug interaction:Drug interaction: Rifampin decrease NVPRifampin decrease NVP Use EFV+3TC+D4TUse EFV+3TC+D4T Must provide birth control while on EFVMust provide birth control while on EFV

RIF levels ARV levels

Nevirapine unchanged ↓ 58%

Efavirenz unchanged ↓ 26%

Ritonovir unchanged° ↓ 35%

Saquinavir NR* ↓ 70%sgc 80%hgc

Indinavir NR* ↓ 90%

Nelfinavir NR* ↓ 82%

Amprenavir NR* ↓ 81%

Change in AUC: Interaction between RIF+ARV

AIDS Read 10(2):102-108, 2000. Adapted with permission from Burman WJ et al. Clin Infect Dis. 1999.

Rifampicin + Efavirenz

• YES. But optimal dosage unclear.

• Rifampin decreases EFV 28%

• Unclear if dose adjustment needed– Spanish study: ↑EFV from 600mg to

800mg overcomes PK1

– Descriptive studies supporting both 600 and 800 mg dose2,3

1. Lopez-Cortes L, Valderas R, Viciana P, et al. Pharmacokinetic interactions between efavirenz and rifampicin in HIV-infected patients with tuberculosis. Clinical Pharmacokinetics 2002; 41 (9):681-690.

2. Lopez-Cortes L,et al. Efficacy, safety, and pharmaco-kinetics of efavirenz (EFV) 800 mg qd co-adminstrated with rifampin (R) in HIV-infected patients with tuberculosis, 2nd IAS Conference on HIV Pathogenesis and Treatment, Paris, France, July 13-16, 2003. Vol. 8.

3. Patel A, et al. To study the safety and antiretroviral efficacy of concomitant use of rifampicin and efavirenz in antiretroviral-naive tuberculosis co-infected HIV-1patients in India, 10th Conference on Retroviruses and Opportunistic Infections, Boston, Massachusetts, February 10-14, 2003.

Rifampicin + Nevirapine

• UNCLEAR. More data needed.

• Rifampin decreases NVP 31% to 58%

• Little clinical data– Small Spanish cohort (n=32): 74% with

virologic suppression at 15 months1

• More studies needed– Esp. in resource-limited settings

1. Oliva J, Moreno S, Sanz J, et al. Co-administration of rifampin and nevirapine in HIV-infected patients with tuberculosis. Aids 2003; 17:637-8.

Rifampicin + PI’s

• NOT RECOMMENDED• Rifampicin decrease protease inhibitor

levels 70-90%• Rifampicin induces hepatic enzyme cytochrome

P450 3A4• Results in MARKED INCREASE in metabolism of

protease inhibitors

• Few clinical studies on PI + rifampicin– Kaletra (lopinavir/ritonavir): variable Cmin.

– Saquinavir/ritonavir tried

PI’s in TB: Additive Toxicity– SQV/rit 1600/200 has been tried1

• High dose PI “boosted” with ritonavir– Ritonavir used to increase PI levels by inhibiting

CYP3A4

• 3/20 with viral rebound, all with low Cmin

– High hepatotoxicity with RIF + SAQ/RIT• Reported February 2005 in Dear Doctor letter• Phase I study: RIF 600mg + SAQ 1000mg + RIT

100mg• 11/28 (39.3%) developed hepatotoxicity

– Transaminases up to 20x upper limit normal

• Ritonavir + rifampin additive hepatotoxicity1. Veldkamp AI, et al. Ritonavir enables combined therapy with rifampin and saquinavir. Clin Infect Dis 1999; 29:1586.

Summary Points

• HIV potentiates TB. TB accelerates HIV

• Treating HIV-TB coinfection is complex– Many clinical questions remain– Rifampicin decreases levels of PI and NNRTI– NRTI levels unchanged.– Additive toxicity with some ARVs and TB therapy

• ARV recommendation in TB therapy– EFV 600mg or 800mg is best option– NVP not well studied, levels decreased somewhat– PIs levels decreased significantly

» Additive toxicity» Beware of hepatotoxicity, failure due to insufficient levels

I. d4T + 3TC + NVP

III. d4T + 3TC + EFV IV. AZT + 3TC + EFVII. AZT + 3TC + NVP

Replace NVP with EFV due to:• Hepatoxicity• NVP intolerance• TB patient on rifampicin

Replace d4T with AZT due to:• Peripheral neuropathy and NO anaemia

Replace NVP with EFV due to:• Hepatoxicity• NVP intolerance• TB patient

Replace d4T with AZT due to:

• Peripheral neuropathy and NO anaemia

Modified 1st line regimen

1st line regimen

Algorithm for selecting first line treatment

Summary

Understand Toxicity of Individual ARV

If symptoms develop, consider each individual ARV and what it can cause

Also consider non-ART related causes Therapy switch

For Toxicity of Complication of ART OK to switch within class

• NVP EFV• D4T AZT or ABC• NVP should NOT be switched for D4T, AZT, DDI,

ABC!