Elvitegravir concentrations in seminal plasma in HIV-1-infected men

作者：Imaz A^*; Niubo J; Kashuba A D; Ferrer E; Sykes C; Rozas N; Acerete L; Vila A; Podzamczer D

来源：HIV Medicine, 2017, 18(3): 225-230.

DOI：10.1111/hiv.12417

• antiretroviral therapy
• elvitegravir
• HIV
• HIV antiviral pharmacology
• HIV reservoirs
• male genital tract
• seminal plasma

Objectives
The aim of the study was to quantify elvitegravir (EVG) concentrations in the semen of HIV-1-infected men receiving antiretroviral therapy (ART) consisting of an elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) single-tablet regimen.
Methods
A phase IV, cross-sectional study was carried out including HIV-1-infected male adults with suppressed plasma HIV-1 RNA who switched ART to EVG/COBI/FTC/TDF. Total EVG concentrations at the end of the dosing interval (C-24 (h)) and HIV-1 RNA were measured in paired seminal plasma (SP) and blood plasma (BP) samples 4 weeks after switching to EVG/COBI/FTC/TDF. Validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify EVG concentrations, and HIV-1 RNA was determined by real-time polymerase chain reaction (PCR).
Results
Ten men were included. Their median age was 40 years (range 24-47 years), the median time on ART was 50 months (range 10-186 months), the median time with plasma HIV-1 RNA < 40 copies/mL was 37 months (range 7-113 months), and the median CD4 count was 737 cells/mu L (range 190-1122 cells/mu L). Four weeks after switching to EVG/COBI/FTC/TDF, all subjects had HIV-1 RNA < 40 copies/mL in both BP and SP. Median EVG C-24 (h) was 277 ng/mL (range 64.8-1790 ng/mL) in BP and 169 ng/mL (range 12.8-792 ng/mL) in SP. A significant correlation was observed between BP and SP EVG concentrations (Spearman rho 0.952; P < 0.001). The median SP:BP EVG concentration ratio was 0.39 (range 0.20-0.92). EVG C-24 h in SP was at least 23-fold the in vitro protein-unbound 50% effective response (EC50) of HIV-1 clinical isolates (0.04-0.55 ng/mL). In all but one individual, EVG C-24 h in SP was also higher than the blood plasma protein binding-adjusted 95% inhibitory concentration (IC95) of wild-type HIV-1 (45 ng/mL).
Conclusions
Seminal EVG concentrations in HIV-infected men treated with EVG/COBI/FTC/TDF sufficed to contribute to maintaining HIV-1 RNA suppression in this compartment.

• 出版日期2017-3