CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: In this diverse group of women undergoing intensive TFV PK sampling, we found a strong and significant association between higher TFV exposure over time and faster declines in subsequent kidney function longitudinally. Variations in tenofovir drug exposure, although rarely assessed, may partially account for subsequent nephrotoxicity in HIV-infected patients. 793 Impact of TDF+PI/r on Renal Function in Sub-Saharan Africa : 2LADY/ANRS 12169 Trial Arsene Hema 1 ; Amandine Cournil 2 ; Laura Ciaffi 2 ; Sabrina Eymard-Duvernay 2 ; Assane Diouf 3 ; Nestor Manga 4 ;Vincent Le Moing 2 ; Jacques Reynes 2 ; Sinata Koulla-Shiro 5 ; Eric Delaporte 2 1 CHU Souro Sanou, Bobo Dioulasso, Burkina Faso; 2 IRD/UM 1, Montpellier, France; 3 Le Centre Régional de Recherche et de Formation à la Prise en Charge Clinique de Fann, Dakar, Senegal; 4 Yaounde Military Hospital, Yaounde, Cameroon; 5 FMSB/University Yaounde 1, Yaounde, Cameroon Background: A strong genetic susceptibility to chronic kidney disease (CKD) has been observed in sub-Saharan African populations. The current WHO-recommended second line antiretroviral treatment (ART) associates a protease inhibitor boosted with ritonavir (PI/r) in combination with Tenofovir Disoproxil Fumarate (TDF) or Zidovudine (AZT) + lamivudine or emtricitabine (FTC). TDF + PI/r has been associated with proximal tubular dysfunction and CKD. The aimwas to determine if TDF+PI/r use was associated with changes in renal function in HIV patients starting a second line ART in comparison with a regimen without TDF (abacavir (ABC) + didanosine (ddI) + LPV/r) in three African countries (Cameroun, Senegal and Burkina Faso). Methods: HIV-1 positive adults, failing standard first line ART were randomized to either A: TDF+FTC+LPV/r; B: ABC + ddI + LPV/r or C: TDF + FTC + darunavir (DRV) /r and followed until 18 months. Patients with an MDRD-estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1,73m 2 were included in this analysis. We compared levels and changes in eGFR using multivariable linear regressions. First occurrence of CKD (eGFR<60ml/ml/1,73m 2 ) was compared using Mantel-Haenszel tests. Results: Out of 454 randomized patients, 443 were included in this analysis. Mean age was 39 years (SD: 9.7) and 72%were women. Thirty-nine patients (9%) had hypertension and 2 (0.4%) diabetes. Median follow-up was 16 months. The rate of decline of eGFR from baseline to week 4 was marked in all treatment groups with a greater mean decrease in TDF+FTC+LPV/r arm (-16.6 ml/min/1.73m 2 ) than in ABC+DDI+LPV/r arm (-8.2; P=10 -3 ); and TDF+FTC+DRV/r arm (-9.6; P=10 -3 ). Fromweek 4 to month 18, mean eGFR remained stable in TDF+FTC+DRV/r and increased in the other two arms. The greatest increase was observed in ABC+DDI+LPV/r (+10.4). At month 18, mean eGFR in the non-TDF containing regimen (112.3) recovered its baseline level and was significantly greater than eGFR 18-month-levels in the TDF-containing regimens (with LPV/r; 100.8; P=5.10 -3 ; with DRV/r; 104.9; P=0.02). Incidence of CKD was 5%; 5% and 4% person-year in arms A, B and C, respectively and did not differ by treatment arms (P=0.78).

Poster Abstracts

eGFR changes by treatment arm Conclusions: Randomization to TDF+IP/r was associated with a mild non progressive decrease of eGFR after 18 months in patients with eGFR>60ml/ml/1,73m 2 at baseline. These results suggest a good renal tolerance of the second line associating TDF+FTC+IP/r in patients in sub-Saharan Africa. 794 Renal Tubular Disease and the RelationshipWith Tenofovir and Atazanavir Exposure Lisa Hamzah 1 ; John Booth 2 ; Catherine Horsfield 3 ; Rachael Jones 4 ; Jeremy Levy 5 ; DeborahWilliams 6 ; Nadia Khatib 7 ; Rachel Hilton 3 ; John Connolly 2 ; Frank A. Post 8 1 King’s College London, London, United Kingdom; 2 University College London, London, United Kingdom; 3 Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom; 4 Chelsea and Westminster Hospital, NHS Foundation Trust, London, United Kingdom; 5 Imperial College London, London, United Kingdom; 6 Brighton and Sussex Hospitals NHS Trust, London, United Kingdom; 7 Heart of England NHS Foundation Trust, Birmingham, United Kingdom; 8 King’s College Hospital NHS Foundation Trust, London, United Kingdom Background: Renal tubular dysfunction is common in HIV+ patients treated with antiretroviral therapy (ART). The pathological spectrum of renal tubular disease (RTD) and its association with ART remains poorly described. Methods: We reviewed 265 consecutive renal biopsies (2000-2012) of HIV+ patients attending 8 clinics in the UK. We describe the clinical characteristics of patients with RTD and compared current/recent exposure (at the time of, or up to 3 months prior to the date of biopsy) to potentially nephrotoxic ART (tenofovir [TDF], atazanavir [ATV], indinavir [IDV] and lopinavir [LPV]) in 54 RTD cases and 64 patients with immune complex kidney disease (ICKD). Kruskall-Wallis, Chi squared, Fisher’s exact tests and Mantel-Haenszel methods were used to evaluate between group differences and calculate odds ratios (OR). Results: RTD could be classified into 3 distinct patterns: acute tubular injury (ATI, n=22), tubulointerstitial nephritis (TIN, n=20) and interstitial fibrosis and tubular atrophy (IFTA, n=12). Compared with TIN and IFTA, ATI cases were less likely to be of black ethnicity (10 vs. 55 and 42%, p=0.006) and more likely to be on ART (100 vs. 55 and 68%, p=0.001) with HIV RNA <200 copies/mL (100 vs. 54 and 58%, p<0.001) at biopsy. There were no significant differences between other HIV and renal parameters in patients with ATI, TIN and IFTA, including median time since HIV diagnosis (11, 4 and 13 years), CD4 nadir (154, 102 and 87 cells/mm 3 ), current CD4 count (364, 262 and 227 cells/mm 3 ), eGFR (47, 25 and 42 mL/ min/1.73m 2 ) and proteinuria (1.4, 1.8 and 1.2 g/24h). 5 ATI cases had biochemical evidence of proximal tubulopathy/Fanconi syndrome vs. none with TIN or IFTA. With resolution, renal function returned to baseline in 77, 50 and 58% of subjects. Compared with ICKD cases, patients with ATI were more likely to have current/recent exposure to TDF (OR [95% CI] 9.8 [2.6, 36.7]), p<0.001), ATV (OR 7.8 [1.2, 50.2]), p=0.01) or LPV (OR 3.3 [1.0, 10.9], p=0.04). No consistent ART associations were observed with TIN or IFTA.

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CROI 2015