CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Poster and Themed Discussion Abstracts

411 EFFECT OF COBICISTAT ON TENOFOVIR PLASMA CONCENTRATION: A CROSS-SECTIONAL STUDY Cristina Gervasoni 1 , Davide Minisci 1 , Sara Baldelli 1 , Cristina Mazzali 2 , Andrea Giacomelli 1 , Laura Milazzo 1 , Paola Meraviglia 1 , Emilio Clementi 1 , Massimo Galli 1 , Dario Cattaneo 1 1 Luigi Sacco Univ Hosp, Milano, Italy, 2 Politecnico di Milano, Italy, Milano, Italy Background: The dose of tenofovir alafenamide (TAF) is reduced from 25 to 10 mg daily when given with cobicistat (COBI) or ritonavir due to the boosting effects of these drugs on tenofovir levels. However, such dose reduction has never being adopted for tenofovir disoproxil fumarate (TDF). Accordingly, the observed less nephrotoxicity of TAF versus TDF could have been driven, at least in part, by inappropriate dose selection for drugs comparison. We aim at providing data on the effect of COBI on tenofovir concentrations in real-life settings. Methods: A cross-sectional analysis was conducted in HIV-positive patients from our database receiving TDF-containing antiretroviral therapies (ART) for at least one month and with at least one assessment of tenofovir plasma trough concentrations. Uni- and multivariate regression analyses were carried out considering tenofovir concentration as the dependent variable and clinical characteristics of the enrolled patients as independent covariates. A general linear model to analyze the effect of independent variables on tenofovir concentrations was applied. Independent variables with p-values < 0.20 at univariate analysis where introduced in the multivariate model Results: Overall, 510 HIV-infected patients were identified from our dataset. These patients were given TDF in combination with PIs/ritonavir (n=212, 41.6%), NNRTIs (n=176, 34.5%), INIs (dolutegravir or raltegravir, n=46, 9.0%) or with elvitegravir/COBI coformulation (n=76, 14.9%). As shown in Table 1, the covariates that resulted significantly associated with elevated tenofovir plasma trough concentrations were patients’ age, body weight, sex, serum creatinine levels and concomitant ART. The highest drug concentrations were measured in patients given elvitegravir/COBI (161±113 ng/mL), being significantly higher than values measured in patients given PIs/ritonavir (147±125 ng/ mL), INIs (113±74 ng/mL) or NNRTIs (109±62 ng/mL) Conclusion: We firstly confirmed the importance of some clinical covariates in predicting tenofovir overexposure. We also provided solid evidence that coadministration with COBI, ihibiting specific influx/efflux drug transporters , resulted in significantly higher tenofovir concentrations compared with all other ART. Accordingly, it could be hypothesized that the lack of dose adjustment for TDF when given with COBI (or with ritonavir) could have introduced a bias in the comparison of safety between TAF and TDF in the current randomized trials

412 MULTIPLE-DOSE TREATMENT WITH RITONAVIR INCREASES THE EXPOSURE OF DORAVIRINE Sauzanne Khalilieh 1 , Matt Anderson 1 , Tine Laethem 2 , Kelly Yee 1 , Rosa Sanchez 1 , Li Fan 1 , Monali Sura 1 , Luc Van Bortel 3 , Greit Van Lancker 3 , Marian Iwamoto 1 1 Merck & Co, Inc, Kenilworth, NJ, USA, 2 MSD Belgium, Brussels, Belgium, 3 Ghent Univ Hosp, Ghent, Belgium Background: Doravirine is a novel, potent, HIV-1 non-nucleoside reverse transcriptase inhibitor in development that is primarily metabolized by oxidation via CYP3A4. Ritonavir (RTV) is both an inhibitor of CYP3A and a general inducer of enzymes that may metabolize doravirine. The objective of this study was to assess the effect of multiple doses of RTV on the pharmacokinetics (PK) of doravirine.

CROI 2017 169