This case study describes a 35-year-old man who presented with end-stage AIDS and liver disease requiring possible liver transplantation. He had HIV for over 10 years, as well as hepatitis B and C. His CD4 count was 69 and viral load was over 100,000. He had severe ascites, high bilirubin, low albumin, and elevated INR. After starting antiretroviral therapy, his viral load decreased and CD4 increased, allowing him to undergo liver transplantation. He had an uneventful recovery and suppression of both HIV and HBV.

1. Case Reports on Long term Survivors D.T Jayaweera M.D. Professor of Medicine Infectious Diseases University of Miami School of Medicine

2. Case Study - 1

7. Child-Pugh Score

8. Child-Pugh Score Calculator Measure 1 point 2 points 3 points units Bilirubin <34 (<2) 34-50 (2-3) >50 (>3) μ mol/l (mg/dl) Albumin >35 28-35 <28 g/l INR <1.7 1.71-2.20 > 2.20 no unit Ascites None Mild Severe no unit Encephalopathy None Grade I-II (or suppressed with medication) Grade III-IV (or refractory) no unit

14. Is HBsAg present? Is IgM anti-HBc present? Is HBeAg or HBV DNA present? Is anti-HBs present? Chronic Hepatitis Acute Hepatitis Replicative HBV infection Non-replicative HBV infection Recovered or vaccinated +/- anti-HBc No HBV infection No Yes Yes Yes Yes No No No Anti-HBc +/- no yes

15. Clinical Liver Disease and HBV Genotype Duong TN, et al. Journal of Medical Virology. 2004;72:551–557. Diagnosis, n (%) Genotypes N Asymptomatic carrier Chronic hepatitis Liver cirrhosis HCC Genotype A 11 8 (72.7) 3 (27.3) 0 0 Genotype B 14 10 (71.4) 3 (21.4) 0 1 (7.2) Genotype C 350 129 (36.8) 126 (36.0) 50 (14.3) 45 (12.9) Genotype D 38 32 (84.2) b 6 (15.8) a 0 0 a a P <0.05 vs genotype C. b P <0.001 vs genotype C.

18. Management Roadmap According to 24 Week Virologic Response Add another drug without cross resistance Monitor every 3 months Add another drug or Continue Monitor every 3 months Continue Monitor every 6 months Inadequate response >10 4 copies/mL Complete response <300 copies/mL Partial response 300-10 4 copies/mL Week 24: Early predictors of efficacy Keeffe et al. Clin Gastroenterol Hepatol, 2007

26. ARTEMIS: Darunavir + Ritonavir Versus Lopinavir/Ritonavir Mills A, et al. 48 th ICAAC. Washington, DC, 2008. Abstract H-1250c. All patients received emtricitabine/tenofovir DF. Virologic failure: >50 copies/mL. * P =0.0437 versus lopinavir/r. † P <0.001 for non-inferiority to lopinavir/r. ‡ P =0.023 versus lopinavir/ritonavir. Week 96 Outcomes Darunavir + RTV (n=343) Lopinavir/r (n=346) Virologic failure (%) 12* 17 HIV RNA <50 copies/mL (%) 79 † 71 By baseline HIV RNA <100K copies/mL > 100K copies/mL 81 (n=226) 76 ‡ (n=117) 75 (n=226) 63 (n=120)

27. ARTEMIS: 96-Week Tolerability Results All patients received emtricitabine/tenofovir DF. * P <0.001 versus lopinavir/r. † P =0.0016 versus lopinavir/r. ‡ P <0.0001 versus lopinavir/ritonavir. Mills A, et al. 48 th ICAAC. Washington, DC, 2008. Abstract H-1250c. Darunavir + RTV (n=343) Lopinavir/r (n=346) Grade 2-4 adverse events Diarrhea Nausea Rash (all types) 4* 2 3 11 3 1 Grade 2-4 lipid abnormalities Total cholesterol LDL-C Triglycerides 18 † 18 4 ‡ 28 15 13

31. Case Study - 2

46. A5224s design: Metabolic substudy of A5202 A5224s

47. LIPIDS A5202: ATV/r vs. EFV Median Changes in Fasting Lipids (mg/dL) In low HIV RNA stratum, in comparison between ABC/3TC vs. TDF/FTC: significantly greater increase in TC, LDL, HDL with both EFV and ATV/r; greater increase in TG with ATV/r Median Change in Fasting Lipids (Week 48, mg/dL) Daar E, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 59LB. TC LDL HDL TG ABC/3TC ATV/r 29 13 8 24 EFV 40 21 12 15 P-value <0.001 0.002 <0.001 0.26 TDF/FTC ATV/r 10 2 5 14 EFV 22 10 8 13 P-value <0.001 0.002 <0.001 0.26

50. D.T Jayaweera M.D. Professor of Medicine Infectious Diseases Thank You