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Track B Workshop Controversies in the Management of HIV-positive Adults: A Case-Based Approach

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

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  1. 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)

  2. HIV Drug Resistance and Treatment Failure

  3. 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

  4. HIV Drug Resistance Testing before ART • A. Yes • B. No

  5. 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

  6. HIV Drug Resistance Testing before ART • A. Yes • B. No

  7. Primary HIVDR in Your Setting/Country? A. <1% B. 1-5% C. 6-10% D. >10% E. No idea!!!

  8. 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)

  9. 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.

  10. 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

  11. 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

  12. Case • May 08: TDF + 3TC + NVP • Sep 08: CD4 count 75 cells/mm3, HIV VL 2,909 copies/mL • Genotypic resistance testing II

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

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