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Track B Workshop Controversies in the Management of HIV-positive Adults: A Case-Based Approach. Sasisopin Kiertiburanakul, MD, MHS Associate Professor Department of Medicine Faculty of Medicine Ramathibodi Hospital Mahidol University. 7 th IAS, Kuala Lumpur (July 1, 2013).
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Track B Workshop Controversies in the Management of HIV-positive Adults: A Case-Based Approach Sasisopin Kiertiburanakul, MD, MHS Associate Professor Department of Medicine Faculty of Medicine Ramathibodi Hospital Mahidol University 7th IAS, Kuala Lumpur (July 1, 2013)
Case • 41-year-old policeman • No known underlying disease • May 08: weight lost, anti-HIV positive • No history of opportunistic infections • CD4 count 35 cells/mm3 • HBsAg: negative • Married for 10 years • No condom use • Going to start ART
HIV Drug Resistance Testing before ART • A. Yes • B. No
His Wife • Diagnosed of HIV infection, PCP, pulmonary TB, cryptococcal meningitis and CMVR in 2004 • Nadir CD4 count 57 cells/mm3 • First regimen in 2005: d4T/3TC/NVP • May 07: CD4 count 106 cells/mm3, HIV VL 27,100 copies/mL • V75I, K101E, M184V, G190A • Change to AZT + ddI + LPV/r • April 08: CD4 count 144 cells/mm3, HIV VL 19,500 copies/mL • I13V, K20R, M36I, H69K, L89M
HIV Drug Resistance Testing before ART • A. Yes • B. No
Primary HIVDR in Your Setting/Country? A. <1% B. 1-5% C. 6-10% D. >10% E. No idea!!!
Primary HIVDR in Asia • ART-naïve patients enrolled in the TREAT Asia Studies to Evaluate Resistance, 2007-2010 • 11 sites, 5 countries Kiertiburanakul S, et al. Plos One 2013 (in press)
HIV Drug Resistance Testing Recommendation *Especially if exposure to someone receiving antiretroviral drugs is likely or if prevalence of drug resistance in untreated patients ≥5% (European: ≥10%). 1. Thompson MA, et al. JAMA 2012;308:387-402. 2. DHHS Guideline, February 2013. Available at: http://www.aidsinfo.nih.gov. 3. Vandamme A, et al. AIDS Rev 2011;13:77-108. EACS Guideline, November 2012. Available at: http://www.europeanaidsclinicalsociety.org. 4. Bureau of AIDS, TB, and STIs and Thai AIDS Society (TAS). Asian Biomed 2010;4:515-28. 5. 2010 WHO Guideline.
HIV Genotype before ART Resistance-associated RT Mutations: No relevant mutations detected Nucleoside and Nucleotide RT Inhibitors Resistance Interpretation abacavir (ABC) No Evidence of Resistance didanosine (ddI) No Evidence of Resistance lamivudine (3TC)/emtricitabine (FTC) No Evidence of Resistance stavudine (d4T) No Evidence of Resistance tenofovir (TDF) No Evidence of Resistance zidovudine (AZT) No Evidence of Resistance Non-nucleoside RT Inhibitors Resistance Interpretation efavirenz (EFV) No Evidence of Resistance nevirapine (NVP) No Evidence of Resistance Resistance-associated PR Mutations: L10I/V, I13V, I15V, G16E, K20I, M36I, H69K, L89M Protease Inhibitors Resistance Interpretation amprenavir (APV)/fosamprenavir (FPV) No Evidence of Resistance APV/r or FPV/r Resistance atazanavir (ATV) Possible Resistance ATV/r No Evidence of Resistance darunavir + ritonavir (DRV/r) No Evidence of Resistance indinavir (IDV) No Evidence of Resistance IDV/r No Evidence of Resistance lopinavir + ritonavir (LPV/r) No Evidence of Resistance nelfinavir (NFV) No Evidence of Resistance saquinavir + ritonavir (SQV/r) Resistance tipranavir + ritonavir (TPV/r) Possible Resistance
First ARV Regimen for Him? • A. TDF + 3TC/FTC + EFV • B. TDF + 3TC/FTC + LPV/r • C. TDF + ABC + LPV/r • D. TDF + AZT + DRV/r • E. ETR + DRV/r + RAL Baseline HIV VL 29,655 copies/mL • His wife HIV resistance mutations • May 07: V75I, K101E, M184V, G190A • April 08: I13V, K20R, M36I, H69K, L89M • d4T/3TC/NVP AZT + ddI + LPV/r with detectable HIV VL
Case • May 08: TDF + 3TC + NVP • Sep 08: CD4 count 75 cells/mm3, HIV VL 2,909 copies/mL • Genotypic resistance testing II
Resistance-associated RT Mutations: K65R, K101E, G190S Nucleoside and Nucleotide RT Inhibitors Resistance Interpretation abacavir (ABC) Possible Resistance didanosine (ddI) Possible Resistance lamivudine (3TC)/emtricitabine (FTC) Possible Resistance stavudine (d4T) No evidence of Resistance tenofovir(TDF) Resistance zidovudine (AZT) No evidence of Resistance Non-nucleoside RT Inhibitors Resistance Interpretation efavirenz(EFV) Resistance nevirapine (NVP) Resistance Resistance-associated PR Mutations: I13V, I15V, G16E, K20I, M36I, H69K, L89M Protease Inhibitors Resistance Interpretation atazanavir (ATV) No Evidence of Resistance ATV/r No Evidence of Resistance darunavir + ritonavir (DRV/r) No Evidence of Resistance fosamprenavir (FPV) No Evidence of Resistance FPV/r No Evidence of Resistance indinavir (IDV) No Evidence of Resistance IDV/r No Evidence of Resistance lopinavir + ritonavir (LPV/r) No Evidence of Resistance nelfinavir (NFV) No Evidence of Resistance saquinavir + ritonavir (SQV/r) Possible Resistance tipranavir + ritonavir (TPV/r) No Evidence of Resistance
What Is The Next Regimen (Backbone)? • AZT + TDF D. AZT only • AZT + 3TC E. No NRTIs • AZT + ABC Current regimen: TDF + 3TC + NVP Resistance-associated RT Mutations: K65R, K101E, G190S Nucleoside and Nucleotide RT Inhibitors Resistance Interpretation abacavir (ABC) Possible Resistance didanosine (ddI) Possible Resistance lamivudine (3TC)/emtricitabine (FTC) Possible Resistance stavudine (d4T) No evidence of Resistance tenofovir(TDF) Resistance zidovudine (AZT) No evidence of Resistance Non-nucleoside RT Inhibitors Resistance Interpretation efavirenz(EFV) Resistance nevirapine (NVP) Resistance
What Is The Next Regimen (Others)? • Boosted PI • Boosted PI + ETR • Boosted PI + RAL • Boosted PI + RAL + ETR • MVC + RAL + ETR ETR score = 2.5 (intermediate response) Resistance-associated RT Mutations: K65R, K101E, G190S Nucleoside and Nucleotide RT Inhibitors Resistance Interpretation abacavir (ABC) Possible Resistance didanosine (ddI) Possible Resistance lamivudine (3TC)/emtricitabine (FTC) Possible Resistance stavudine (d4T) No evidence of Resistance tenofovir(TDF) Resistance zidovudine (AZT) No evidence of Resistance Non-nucleoside RT Inhibitors Resistance Interpretation efavirenz(EFV) Resistance nevirapine (NVP) Resistance
Case • May 08: TDF + 3TC + NVP • Sep 08: CD4 count 75 (4%) cells/mm3, HIV VL 2,909 copies/mL • Genotypic resistance testing II • Oct 08: change to AZT/3TC, LPV/r • Feb 09, Jun 09: HIV VL <40 copies/mL • Dec 10: CD4 count 261 (15%) cells/mm3, HIV VL <40 copies/mL
Case • Sep 11: CD4 count 291 cells/mm3, HIV VL <40 copies/mL • Lipodystrophy: change to TDF/FTC, LPV/r • Nov 11: CD4 count 370 cells/mm3, HIV VL <40 copies/mL • Nov 12: CD4 count 372 cells/mm3, HIV VL <20 copies/mL • June 13: CD4 count 389 cells/mm3, HIV VL <20 copies/mL
The HIVSecond-line Therapy AntiRetroviral study in patients who failed NNRTI-based regimens * Multi-NRTI mutations were defined as having ≥4 thymidine analog mutations (TAMs) or Q151M complex or 69insertion BunupuradahT, et al. AntivirTher 2012;17:1351-61.
100 90 80 70 HIV-RNA ≥400 copies/mL 60 HIV-RNA <400 copies/mL HIV-RNA <200 copies/mL 50 % Virological suppression HIV-RNA <50 copies/mL 40 30 20 10 0 Mono-LPV/r-arm TDF/3TC/LPV/r-arm BunupuradahT, et al. AntivirTher 2012;17:1351-61.
Take Home Message • Routine HIVDR testing prior to ART initiation may become consideration • Local prevalence of primary HIVDR • Possibility to acquire HIV drug resistance • Limited options of the 2nd line regimen in a resource limited setting