CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

650 FACTORS ASSOCIATED WITH RAPID EGFR DECLINE IN PATIENTS RECEIVING TDF AND/OR ATV Lisa Hamzah 1 , Sophie Jose 2 , Rachael Jones 3 , Deborah Williams 4 , David Chadwick 5 , Andrew Phillips 2 , Caroline Sabin 2 , Frank Post 6 1 King’s Coll Hosp, London, UK, 2 Univ Coll London, London, UK, 3 Chelsea and Westminster NHS Fndn Trust, London, UK, 4 Brighton and Sussex Univ Hosps, Brighton, UK, 5 South Tees Hosps NHS Fndn Trust, Middlesbrough, UK, 6 King’s Coll Hosp NHS Fndn Trust, London, UK Background: Rapid estimated glomerular filtration rate (eGFR) decline is a risk factor for cardiovascular events in diabetics and for mortality in the general population. In HIV- positive people, tenofovir (TDF) and atazanavir (ATV) have been associated with rapid eGFR decline. We analysed risk factors for, and mortality associated with, rapid eGFR decline in subjects receiving TDF and/or ATV. Methods: Individuals in UK CHIC with a first episode of either TDF or ATV exposure since 1/1/2000 with ≥1 year exposure and ≥1 creatinine value (excluding first 3 months after TDF/ATV start) were considered for analysis. Despite overlap, periods of TDF and ATV exposure were analysed separately. eGFR slopes were generated for each group using mixed effects models adjusted for age, ethnicity and sex; individuals with rapid eGFR decline (>3mL/min/1.73m²/year) were identified. Demographic and HIV factors associated with rapid eGFR decline for those on TDF and ATV were analysed using logistic regression, and factors associated with all-cause mortality using Poisson regression. Results: 16172 individuals commenced TDF (mean age 38 years, 73%white, 79%male, mean eGFR at TDF start 82 mL/min/1.73m², 21% co-administered with ATV) and 4162 commenced ATV (mean age 37 years, 68%white, 72%male, mean eGFR at ATV start 80, 81% co-administered with TDF). Adjusted eGFR slopes (95% CI) for TDF and ATV were -0.26 (-0.33, -0.19) and -0.61 (-0.79, -0.43) respectively; 15.8% of those on TDF and 21.7% of those on ATV experienced rapid eGFR decline. In adjusted analyses, rapid eGFR decline was associated with black ethnicity, lower baseline eGFR and shorter TDF/ATV exposure (Table 1). In addition, younger age, AIDS and co-exposure to ATV/lopinavir (LPV) in the TDF group and female sex and TDF exposure in the ATV group were associated with rapid decline. During a mean (SD) follow up of 8.0 (4.8) years, 573 died. After adjustment for age, sex, ethnicity, nadir CD4, hepatitis status, baseline eGFR and ART regimen, rapid eGFR decline remained associated with all-cause mortality (aHR [95% CI] 1.56 [1.27, 1.92] and 1.83 [1.31, 2.56] for TDF and ATV respectively, p<0.001). Similar results were obtained when rapid eGFR decline was defined as >5 mL/min/1.73m²/year. Conclusion: Rapid eGFR decline was observed in a substantial proportion of those who received TDF or ATV and identified a subset of patients at increased risk of death. Black ethnicity, lower baseline eGFR, TDF/ATV and TDF/LPV co-exposure were associated with rapid eGFR decline.

Poster and Themed Discussion Abstracts

651 DISCONTINUATION OF DTG, EVG/C, AND RAL DUE TO TOXICITY IN A PROSPECTIVE COHORT

Josep M. Llibre 1 , Anna Esteve 2 , Jose M. Miro 3 , Gracia Mateo 4 , Adrià Curran 5 , Daniel Podzamczer 6 , Melchor Riera 7 , Francesc Homar 8 , Luis Force 9 , for the PISCIS Cohort Study Group 1 Univ Hosp Germans Trias, Barcelona, Spain, 2 Cntr d’Estudis Epidemiològics Sobre les ITS i Sida de Catalunya, Barcelona, Spain, 3 Univ of Barcelona, Barcelona, Spain, 4 Hosp Sant Pau, Barcelona, Spain, 5 Hosp Vall d’Hebró, Barcelona, Spain, 6 Hosp Univ de Bellvitge, Barcelona, Spain, 7 Hosp Univ Son Espases, Palma de Mallorca, Spain, 8 Hosp Son Llàtzer, Palma de Mallorca, Spain, 9 Hosp de Mataró, Mataró, Spain Background: The rates of discontinuation (D/C) due to adverse events (AEs) of the integrase strand transfer inhibitors (INSTI) dolutegravir (DTG), raltegravir (RAL) and cobicistat- boosted elvitegravir (EVG/c) have been very low in randomized clinical trials. However, some real-life retrospective series have reported unexpectedly high rates of D/C due to AEs, particularly with DTG. We aimed to compare the D/C rates due to AEs of the three INSTI inhibitors in a prospective multicenter cohort. Methods: The PISCIS Cohort is an ongoing observational study that includes about 21000 HIV-infected patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain). All subjects having started one of these 5 regimens including DTG with abacavir/lamivudine (ABC/3TC) or tenofovir fumarate/emtricitabine (TDF/FTC; regimens A and B, respectively), RAL with ABC/3TC (C) or TDF/FTC (D), or the co-formulation EVG/c/TDF/FTC (E) since July 2013 as their initial regimen or a switch with plasma HIV-1 RNA <50 c/ mL were included. The incidence rate and 95% confidence interval [IR (95% CI)] of D/C due to toxicity is estimated as the ratio of the number of discontinuations by 100 patients/ year of follow-up. Adjusted hazard ratios (aHR) and their 95% CI were obtained frommultivariate Cox models, adjusted for gender, age, transmission group, origin, treatment- naïve and hepatitis B/C co-infection. Results: Out of 13066 patients on follow-up at July 2016, 2096 subjects were included (90% naives), receiving regimens A (n=859), B (n=108), C (n=208), D (n=280) and E (n=641). Of them, 430 (stopped prematurely their regimen, due to AEs in 74. The corresponding IR (95%CI) for DTG, RAL and EVG/c were 5.1 (3.6-7.0), 3.0 (1.8-4.5), and 2.8 (1.7-4.1), respectively. Among those receiving DTG, the IR with ABC/3TC or TDF/FTC were 4.9 (3.3-6.9) and 6.3 (2.0-12.9), respectively, with no significant differences between them. The aHR of D/C due to AEs with DTG vs. RAL was 1.1 (0.6-2.1), DTG vs. EVG/c 1.6 (0.8-2.9), and EVG/c vs. RAL 0.8 (0.4-1.6).

CROI 2017 279