1. HIV/renal studies (CHIC) Baseline renal function as predictor of HIV/renal disease progression –Death, opportunistic infection –Severe chronic kidney disease (stages 4-5) Changes in renal function –Accelerated decline in renal function –Chronic kidney disease progression HIV/renal transplantation HIV/Fanconi syndrome

2. Total N (%)19,111 (100) Male N (%)15,09 4(79) Ethnicity N (%)Black4,640 (24) White/Other14, 471 (76) Hepatitis B surface antigen positive N (%)1,097 (6) Hepatitis C antibody positive N (%)1,333 (7) CD4 at time of baseline eGFR (cells/mm 3 )Median (IQR)352 (212, 520) Viral load at time of baseline eGFR (copies/ml)Median (IQR)1995 (50, 32154) Baseline eGFR-MDRD ml/min/1.73m 2 Median (IQR)95 (83, 108) Baseline eGFR-CKD-EPI ml/min/1.73m 2 Median (IQR)100 (87, 112) On cART at time of baseline eGFRN (%)12,034 (62)  Median time from HIV diagnosis to baseline eGFR was 4 [3, 9] months  Median follow-up was 5.7 [IQR: 2.7, 9.1] years  1,837 (9.6%) died; 79 (0.41%) progressed to stage 4/5 CKD Does renal function at baseline predict mortality or progression to stages 4/5 CKD?

3. 0% 25% 50% 75% 100% Cumulative Mortality % 0 5 10 15 Years from entry to the cohort ≥9075-89 60-7430-59 15-29<15 0% 25% 50% 75% 100% 05 1015 Years from entry to the cohort ≥90 60-7430-59 15-29<15 75-89 (a) eGFR-MDRD(b) eGFR-CKD-EPI Time to death in HIV positive patients stratified by baseline eGFR Hamzah et al, BHIVA 2010

4. MDRD CKD-EPI eGFRAdjusted 1 HR (95%CI) P P ≥9011 60-890.93 (0.84, 1.02) 0.13 1.02 (0.92, 1.13) 0.75 30-59 1.98 (1.53, 2.56) <0.001 2.24 (1.72, 2.94) <0.001 15-29 5.31 (3.13, 9.01) <0.001 5.25 (3.04, 9.08) <0.001 <15 6.69 (4.07, 11.00) <0.001 6.90 (4.20, 11.33) <0.001 1 Estimates were adjusted for gender, ethnicity, age at entry to cohort, and AIDS, CD4 cell count and cART at baseline Adjusted mortality hazard ratios (95% CI) stratified by baseline eGFR Hamzah et al, BHIVA 2010

5. MDRD CKD-EPI eGFR Adjusted SHR (95%CI)P P ≥9011 89-753.50 (0.98, 12.6)0.052.17 (0.61, 7.73)0.23 74-6011.86 (3.16, 44.5)<0.00114.0 (4.55, 43.1)<0.001 59-30140.9 (42.4, 463.1)<0.001115.9 (42.1, 319.6)<0.001 Ethnicity Black3.38 (1.58, 7.25)0.0022.52 (1.20, 5.28)0.01 CD4 cell count (cells/mm 3 ) (per 50 cell increase) 0.95 (0.87, 1.04)0.270.95 (0.86, 1.03)0.26 Estimates were adjusted for all the variables in table; SHR= Sub-hazard ratios; CI=Confidence intervals Factors associated with progression to stage 4/5 CKD Hamzah et al, BHIVA 2010

6. HIV/renal studies (CHIC) Baseline renal function as predictor of HIV/renal disease progression –Death, opportunistic infection –Severe chronic kidney disease (stages 4-5) Changes in renal function –Accelerated decline in renal function –Chronic kidney disease progression HIV/renal transplantation HIV/Fanconi syndrome

7. ATV/r vs. EFV Median Change in Creatinine Clearance A5202: Overall: As-Treated Daar, E et al. 17 th CROI 2010. Abstract 59LB

8. 97% 3% Campbell LJ et al, HIV Med 2009; 10:329-36. Annual decline in eGFR

9. Incident CKD in EuroSIDA CKD defined as –confirmed eGFR 60 –>25% decline if baseline eGFR <60 21,482 PYFU –median 3.7 years 225 (3.3%) progressed to CKD –Incidence 1.1 (0.9-1.2) per 100py Mocroft et al. AIDS 2010

11. HIV/renal studies (CHIC) Baseline renal function as predictor of HIV/renal disease progression –Death, opportunistic infection –Severe chronic kidney disease (stages 4-5) Changes in renal function –Accelerated decline in renal function –Chronic kidney disease progression HIV/renal transplantation HIV/Fanconi syndrome

12. HIV-Associated Kidney Disease: ESRF AIDS 2009; 23: 2517-21

13. Fanconi syndrome Prevalence: 1-2% of patients receiving Tenofovir Bone pain Phosphate wasting Osteomalacia Almost exclusively when tenofovir is co-administered with a (boosted) PI