Elvitegravir Concentrations in Seminal Plasma in HIV-1-infected Men

HIV Med. 2017 Mar;18(3):225-230. doi: 10.1111/hiv.12417. Epub 2016 Aug 1.

Abstract

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 (C24 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/μL (range 190-1122 cells/μL). 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 C24 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 C24 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 C24 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.

Keywords: HIV; HIV antiviral pharmacology; HIV reservoirs; antiretroviral therapy; elvitegravir; male genital tract; seminal plasma.

Publication types

  • Clinical Trial, Phase IV
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics*
  • Chromatography, Liquid
  • Cross-Sectional Studies
  • HIV Infections / drug therapy*
  • HIV-1 / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Plasma / chemistry
  • Quinolones / administration & dosage*
  • Quinolones / pharmacokinetics*
  • RNA, Viral / blood
  • Real-Time Polymerase Chain Reaction
  • Semen / chemistry*
  • Tablets / administration & dosage
  • Tandem Mass Spectrometry
  • Young Adult

Substances

  • Anti-HIV Agents
  • JTK 303
  • Quinolones
  • RNA, Viral
  • Tablets