1. IAS–USA Managing Antiretroviral Failure in 2012 Jennifer Hoy, MD Professor of Medicine Director, HIV Medicine The Alfred Hospital FINAL: 07-20-12 Presented by J Hoy, MD, IAS, July 25, 2012.

2. Slide #2 Presented by J Hoy, MD, IAS, July 25, 2012. Phillip, Aged 67 Years HIV infection diagnosed on screening for HBV treatment trial in 1995 Commenced ART 1996, viral load 20,700 c/mL, CD4 count 150 cells/µL AZT + ddI + saquinavir 1996 -1999 (lamivudine initially not tolerated - headaches) Virological failure 1999, VL 43,800 c/mL, CD4 count 160/µL ART regimen changed to NNRTI based regimen – severe rash to nevirapine Stavudine + lamivudine + indinavir/ritonavir

3. Slide #3 Presented by J Hoy, MD, IAS, July 25, 2012. Phillip Stavudine switched for tenofovir in 2002 VL persistently undetectable from 2001-2003 Virological failure 2003 VL 13,000 copies/mL, CD4 count 200 cells/µL HIV genotype M41L, T215Y, M184V, V82A, L90M Adherence difficulties addressed Would not consider efavirenz-based regimen Regimen changed to tenofovir + lamivudine + lopinavir/r Good virological response

4. Slide #4 Presented by J Hoy, MD, IAS, July 25, 2012. Phillip Fasting total and LDL cholesterol markedly and persistently increased VL <50 copies/mL Non-smoker, BMI - 24

5. Slide #5 Presented by J Hoy, MD, IAS, July 25, 2012. How Would You Manage the Hyperlipidemia? 1.Provide dietary and exercise advice and recheck lipids in 2 months 2.Commence atorvastatin 3.Switch lopinavir/r to atazanavir/r 4.Switch all drugs to more lipid-friendly regimen

6. Slide #6 Presented by J Hoy, MD, IAS, July 25, 2012. Phillip 2006 Admitted to hospital with pneumococcal pneumonia Complicated by acute myocardial infarction Started on low dose aspirin, atorvastatin, β-blocker Tenofovir+lamivudine swapped to tenofovir/emtricitabine with atazanavir/r 2008 VL <50 copies/mL, CD4 count 250 cells/µL CD4 count remained between 200 and 250 cells/µL from 2002, despite undetectable VL from 2003

7. Slide #7 Presented by J Hoy, MD, IAS, July 25, 2012. What Strategy will Predictably Increase CD4 Cell Count for Clinical Benefit? 1.Interleukin 2 2.Change the ART regimen to abacavir + lamivudine and efavirenz 3.Intensify his ART regimen with raltegravir 4.None of the above

8. Slide #8 Presented by J Hoy, MD, IAS, July 25, 2012. Phillip Has persistently undetectable viral load until July 2009 Viral load reported to be 750/mL

9. Slide #9 Presented by J Hoy, MD, IAS, July 25, 2012. What Should You Do Now? 1.Immediately change all drugs in his ART regimen 2.HIV genotype – use the results to construct a new regimen 3.Repeat the viral load 4.CCR5 tropism status

10. Slide #10 Presented by J Hoy, MD, IAS, July 25, 2012. Phillip Repeat VL <50 copies/mL Viral blip Adherence strategies emphasized Ensure not missing doses due to poor tolerability/adverse effects of ART regimen VL remains undetectable until December 2010 VL reported at 60 copies/mL

11. Slide #11 Presented by J Hoy, MD, IAS, July 25, 2012. What Should You Do Now? 1.Immediately change all drugs in his ART regimen 2.HIV genotype – use the results to construct a new regimen 3.Repeat the viral load 4.CCR5 tropism status

12. Slide #12 Presented by J Hoy, MD, IAS, July 25, 2012. Phillip Repeat VL 70 copies/mL eGFR gradually decreased from >60 mL/min in 2007 to 40 mL/min 2010 No glycosuria, proteinuria, normal serum phosphate, bicarbonate. Creatinine increased Hepatitis B surface antigen positive HBV DNA undetectable from 2002 to 2010 HIV genotype from 2003 – M41L, T215Y, M184V

13. Slide #13 Presented by J Hoy, MD, IAS, July 25, 2012. What Would You Recommend? 1.Change dosing frequency of tenofovir/emtricitabine for renal impairment 2.Switch tenofovir/emtricitabine to abacavir/lamivudine 3.Stop tenofovir/emtricitabine, use a non-NRTI based regimen 4.Stop tenofovir, add entecavir

14. Slide #14 Presented by J Hoy, MD, IAS, July 25, 2012. Phillip Plasma VL varied between <20 copies/mL and 70 copies/mL for 18 months. VL reported to be 1200 copies/mL in May 2012 Confirmed VL – 1500 copies/mL 2 weeks later

15. Slide #15 Presented by J Hoy, MD, IAS, July 25, 2012. What Would You Do Now? 1.Immediately change all drugs in his ART regimen 2.HIV genotype – use the results to construct a new regimen 3.Add raltegravir or elvitegravir to current ART regimen 4.Change atazanavir/r to raltegravir 5.CCR5 tropism status