Managing Antiretroviral Failure in 2012

1. Managing Antiretroviral Failure in 2012 Jennifer Hoy, MBBSProfessor of MedicineDirector, HIV MedicineThe Alfred Hospital FINAL: 07-20-12

2. 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. 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. Phillip Fasting total and LDL cholesterol markedly and persistently increased VL <50 copies/mL Non-smoker, BMI - 24

5. How Would You Manage the Hyperlipidemia? Provide dietary and exercise advice and recheck lipids in 2 months Commence atorvastatin Switch lopinavir/r to atazanavir/r Switch all drugs to more lipid-friendly regimen

6. 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. What Strategy will Predictably Increase CD4 Cell Count for Clinical Benefit? Interleukin 2 Change the ART regimen to abacavir + lamivudine and efavirenz Intensify his ART regimen with raltegravir None of the above

8. Phillip Has persistently undetectable viral load until July 2009 Viral load reported to be 750/mL

9. What Should You Do Now? Immediately change all drugs in his ART regimen HIV genotype – use the results to construct a new regimen Repeat the viral load CCR5 tropism status

10. 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. What Should You Do Now? Immediately change all drugs in his ART regimen HIV genotype – use the results to construct a new regimen Repeat the viral load CCR5 tropism status

12. 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. What Would You Recommend? Change dosing frequency of tenofovir/emtricitabine for renal impairment Switch tenofovir/emtricitabine to abacavir/lamivudine Stop tenofovir/emtricitabine, use a non-NRTI based regimen Stop tenofovir, add entecavir

14. 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. What Would You Do Now? Immediately change all drugs in his ART regimen HIV genotype – use the results to construct a new regimen Add raltegravir or elvitegravir to current ART regimen Change atazanavir/r to raltegravir CCR5 tropism status