What’s New in What s New in Antiretroviral Therapy? Antiretroviral Therapy? Sasisopin Kiertiburanakul, MD, MHS Division of Infectious Diseases Department of Medicine Faculty of Medicine Ramathibodi Hospital Faculty of Medicine Ramathibodi Hospital Mahidol University Rotating RCPT, Uttaradit (July 8, 2010)
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What’s New inWhat s New in Antiretroviral Therapy?Antiretroviral Therapy?
Sasisopin Kiertiburanakul, MD, MHS
Division of Infectious DiseasesDepartment of Medicine Faculty of Medicine Ramathibodi HospitalFaculty of Medicine Ramathibodi Hospital Mahidol University
Rotating RCPT, Uttaradit (July 8, 2010)
Outline
• Patient evaluation and assessmentPatient evaluation and assessment• When to start• What to start• How to monitorHow to monitor
P ti t E l ti dPatient Evaluation and AssessmentAssessment
History Takingy g
• Estimate the duration of HIV infectionEstimate the duration of HIV infection– Timing of HIV seroconversion? or
Wh th fi t HIV di i ?– When was the first HIV serodiagnosis?• Risk factor• Past HIV-related illness
(cells/mm3) History of AIDS-defining illness Any Treat
Asymptomatic <350 TreatPregnant women* Any TreatHIV-associated nephropathy Any Treat
HBV co-infection when HBV treatment indicated
Any Treattreatment indicated
Asymptomatic without specific conditions above
350-500 55% voted for strong recommendation (A)conditions above recommendation (A)
Asymptomatic without specific conditions above
>500 50% voted favor starting ART (B)
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Department of Health and Human Services. December 1, 2009. http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf
Earlier Initiation of HIV TreatmentBenefit Limitations• Reduction in mortality and/or
immune reconstitution– T-cell activation andT cell activation and
inflammation• Prevention of HIV transmission
CD4 <200 CD4 <350
Other Factors
• Patients’ willingness and readinessPatients willingness and readiness• Adherence potential• Family planning status • Co-morbidity or conditions: OI liverCo morbidity or conditions: OI, liver
disease, depression or mental illness, cardiovascular disease chemicalcardiovascular disease, chemical dependency, pregnancy
• Potential drug interactions with other medicationsmedications
• 2 NRTIs + INSTIntegrase based regimens– Integrase-based regimens
ARV Combinations: Basic Regimens
2 NRTI + NNRTI/Boosted PIs
Non-Thymidine
2 NRTI + NNRTI/Boosted PIs
Thymidine NNRTI orNon Thymidine Analog+
Thymidine Analog
NNRTI orBoosted PIs+
3TCAZTd4T
EFV or NVP
ATV+rDRV/rLPV/
ddIFTC
LPV/r SQV/r
ABCTDF
Thai HIV Guidelines 2010
Recommendation NRTI NNRTI PI
Preferred AZT + 3TC EFV or LPV/rPreferred AZT + 3TC TDF + 3TC TDF/FTC
EFV or NVP
LPV/r
TDF/FTC
Alternative ABC + 3TC d4T 3TC
- ATV/r d4T + 3TC ddI + 3TC
SQV/r DRV/r
Sungkanuparph S et al. Asian Biomed 2010. (in press)
WHO Guideline 2009: Key Messages
• Greater use of more patient-friendlyGreater use of more patient friendly treatment regimensP i l h t f d4T• Progressively phase out use of d4T as a preferred first-line therapy option – Avoid disabling and disfiguring side effects
and reduce costs of managing these toxicitiesg g
• Move to less toxic alternatives such as AZT and TDFAZT and TDF
Alternative (ABC or AZT) + 3TC EFV ATV/rLPV/rLPV/r
AZT + 3TC NVP
TDF/FTC SQV/rTDF/FTC SQV/rLPV/r
Acceptable ddI + (3TC or FTC) EFVp ( )
(ABC or AZT) + 3TC ATV
Use with caution ABC + 3TC or TDF/FTC NVP
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Department of Health and Human Services. December 1, 2009. http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf
• Health insurance systemHealth insurance system • Inexpensive• Access to HIV care• Co-morbidityCo morbidity• Concurrent OI and its treatment• ART during pregnancy• Efficacy• Efficacy
What Not to Use
• Monotherapy with NRTIpy• Dual-NRTI regimens • Triple NRTI regimens (with exception)• Triple-NRTI regimens (with exception) • d4T + ddI• d4T + AZT• TDF + ddI• ATV + IDV• EFV in first trimester of pregnancy• EFV in first trimester of pregnancy• NVP in women with CD4 >250 or men with CD4
400 ll / 3>400 cells/mm3
Common Adverse Effects: NRTIs
• Zidovudine: headache, GI intolerance,Zidovudine: headache, GI intolerance, bone marrow suppressionT f i h d h GI i t l l• Tenofovir: headache, GI intolerance, renal impairment, Fanconi syndrome
• Nevirapine: hepatotoxicity, rash includingNevirapine: hepatotoxicity, rash including Stevens-Johnson syndromeEf i hi t i t t i• Efavirenz: neuropsychiatric, teratogenic, false positive cannabinoid test
40 Years Old Businessman
• Fever, weight loss, and Rt. axilla mass 4Fever, weight loss, and Rt. axilla mass 4 weeksN l CXR• Normal CXR
• CD4 23 cells/mm3• Pus AFB positive
S HRZE• Start HRZE
Q3: 4 weeks Later, What Next?
• A. Wait for another 4 weeks, then startA. Wait for another 4 weeks, then start ARTB W it til l t TB t t t• B. Wait until complete TB treatment
• C. Start ART with NVP-based regimeng• D. Start ART with EFV-based regimen
E S ART i h PI b d i• E. Start ART with PI-based regimen
<200 Start TB treatment Start ART Recommended ART<200 Start TB treatment. Start ART as soon as TB treatment is tolerated (after 2 weeks)
Recommended ART
200-350 Start TB treatment. Start one of the ART regimen after intensive phase of TB
Recommended ART
intensive phase of TB treatment (if severely compromised start earlier)
>350 Start TB treatment Defer ART
ART Regimen in Patients with TB
• EFV containing regimensEFV containing regimens– EFV is contra-indicated in pregnant women or
women of child bearing potential withoutwomen of child bearing potential without effective contraceptionD f EFV i 600 /d f i ht <60– Dosage of EFV is 600 mg/day for weight <60 kg and 800 mg/day for weight >60 kg1
• NVP is an alternative to EFV for patient who has taken rifampicin p– Lead-in NVP for the first 14 days is not
necessarynecessary
1. Sungkanuparph S et al. J Med Assoc Thai 2008;91:1925-36.
Patients with active TB hasnewly diagnosed HIV infectionnewly diagnosed HIV infection
Rifampicin containingRifampicin-containing drug regimen
St t ART t l tART is
not indicated nowART is
indicated
Start ART at least 2 weeks-2 monthsafter TB treatment
ART with EFV based regimen Alternatively useART with EFV-based regimen(alternative NVP-based regimen)
Alternatively use non refampcin-based
drug regimen
Re-evaluated after complete Any standard ART regimensp
TB treatment Any standard ART regimens
HIV/TB Co-infection
HIV-infected PatientsHIV infected PatientsNew active TB established
Continuationof ART
NNRTI-based regimen PI-based regimen g(EFV or NVP)
g
Rifampicin-containing
drug regimen
Alternatively use non rifampicin-containing
drug regimendrug regimen drug regimen
IRIS: Definition
• Immune recovery inflammatory syndrome y y y• Collection of inflammatory disorders associated
with paradoxical worsening of pre-existingwith paradoxical worsening of pre existing infectious processes following the initiation of HAART in HIV-infected individualsHAART in HIV infected individuals
• Systemic or local inflammatory reactions may occur at the site or sites of preexisting infectionoccur at the site or sites of preexisting infection
• Preexisting infections P i l di d d d– Previously diagnosed and treated
– Subclinical and later unmasked by the host's regained it t t i fl tcapacity to mount an inflammatory response
Timing of ART in the Setting of OI
• Early ART in hopes of • Deferring ART in order to d th i k f IRISreducing the risk of AIDS-
Vi l i l it i• Virological monitoring• Drug resistant testingDrug resistant testing• Therapeutic drug monitoring
Monitoring: Thai Guideline 2010gLaboratory During the first year After the first year Noteinvestigations
CBC, CD4 6, 12 month Every 6 month
Viral load First regimen: Every 12 month Before changing the regimen6, 12 month (every 6 month,
if possible)
ART changing after f il 6 12 th
Every 12 monthfailure: 6, 12 month
FBS 6, 12 month Every 6 month
ALT 6, 12 month Every 6 month At 3 month if starting NNRTIs
Cr* 6, 12 month Every 6 month Every 6 month, if use TDF or IDV
Lipid profile (TC, TG, LDL, HDL)
6, 12 month Every 6 month
Urinalysis - - Every 6 month, if use TDF or IDV
CXR - - Repeat, if indicated
Pap smear 12 month Every 12 month Repeat, if indicatedPap smear 12 month Every 12 month Repeat, if indicated
Sungkanuparph S et al. Asian Biomed 2010. (in press)
Laboratory Monitoring Schedule: DHHS
Entry to care Follow up before ART
ART initiation or switchbefore ART or switch
CD4 cell count every 3-6 months
HIV RNA every 3-6 monthsHIV RNAResistance testing optional
Hepatitis B serology if not immune and HBsAg negHBsAg neg
Basic chemistry every 6-12 months
Liver function test every 6-12 months
CBC every 3-6 months
Lipid profile if normal, annually
Fasting glucose if normal, annually
Urinary analysisif t ti EFVPregnancy test if starting EFV
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Department of Health and Human Services. December 1, 2009.http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf
Conclusions
• Appropriate patient assessmentAppropriate patient assessment• Early treatment initiation is associated with
b fit th i kmore benefits than risk– Asymptomatic with CD4 <350 cells/mm3
• Use less toxic drugsA i t ti i f ART i iti ti i• Appropriate timing of ART initiation in patients with OI
• Appropriate monitoring • Patients should be identified early• Patients should be identified early