title: Elvitegravir concentrations in seminal plasma in HIV-1-infected men.
abstract: 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.
  
  
  
  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).
  
  
  
  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 hwas 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 hin 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 hin SP was also higher than the blood plasma protein binding-adjusted 95% inhibitory concentration (IC95) of wild-type HIV-1 (45 ng/mL).
  
  
  
  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.
authors.affiliation: HIV and STD Unit, Department of Infectious Diseases, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Imaz
authors.affiliation: Department of Microbiology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Niubó
authors.affiliation: UNC Center for AIDS Research, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Kashuba
authors.affiliation: HIV and STD Unit, Department of Infectious Diseases, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ferrer
authors.affiliation: UNC Center for AIDS Research, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: C
authors.initials: C
authors.lastname: Sykes
authors.affiliation: HIV and STD Unit, Department of Infectious Diseases, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Rozas
authors.affiliation: HIV and STD Unit, Department of Infectious Diseases, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Acerete
authors.affiliation: HIV and STD Unit, Department of Infectious Diseases, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Vila
authors.affiliation: HIV and STD Unit, Department of Infectious Diseases, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Podzamczer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010949:Plasma / Q000737:chemistry; D015363:Quinolones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012367:RNA, Viral / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D012661:Semen / Q000737:chemistry*; D013607:Tablets / Q000008:administration & dosage; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015363:Quinolones; D012367:RNA, Viral; D013607:Tablets; C509700:elvitegravir
keywords: 
  HIV
  ; HIV antiviral pharmacology; HIV reservoirs; antiretroviral therapy; elvitegravir; male genital tract; seminal plasma