title: HIV-1-RNA Decay and Dolutegravir Concentrations in Semen of Patients Starting a First Antiretroviral Regimen.
abstract: The objective of this study was to quantify human immunodeficiency virus (HIV) type 1 RNA decay and dolutegravir (DTG) concentrations in the semen of HIV-infected patients receiving DTG-based first-line therapy.
  
  
  
  This was a prospective, single-arm, open-label study including 15 HIV-1-infected, antiretroviral therapy-naive men starting once-daily treatment with DTG (50 mg) plus abacavir-lamivudine (600/300 mg). HIV-1 RNA was measured in seminal plasma (SP) and blood plasma (BP) at baseline, on days 3, 7, and 14, and at weeks 4, 12, and 24. The HIV-1 RNA decay rate was assessed using nonlinear mixed-effects models. Total and free DTG concentrations were quantified 24 hours after the dose at weeks 4 and 24 by means of a validated liquid chromatography-tandem mass spectrometry method.
  
  
  
  Viral decay was faster in BP than in SP in the first decay phase (half-life, 4.5 vs 8.6 days; P = .001) with no statistically significant differences in the second phase. HIV-1 RNA suppression (<40 copies/mL) was reached earlier in SP (4 vs 12 weeks; P = .008) due to lower baseline HIV-1 RNA levels. The median total DTG 24 hours after the dose in SP was 119.1 ng/mL (range, 27.2-377 ng/mL), which represents 7.8% of BP exposure. The median DTG free-fraction in SP was 48% of the total drug. Seminal protein-unbound DTG concentrations exceeded the in vitro 50% inhibitory concentration (0.21 ng/mL) by a median of 214-fold.
  
  
  
  DTG concentrations in SP are sufficient to contribute to rapid seminal HIV-1 RNA suppression.
authors: HIV and STD Unit, Department of Infectious Diseases.
authors: Arkaitz
authors: A
authors: Imaz
authors: Institució Catalana de Recerca i Estudis Avançats, Barcelona.|University of Vic-Central University of Catalonia, Vic.|AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors: Javier
authors: J
authors: Martinez-Picado
authors: Department of Microbiology, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat.
authors: Jordi
authors: J
authors: Niubó
authors: UNC Center for AIDS Research, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill.
authors: Angela D M
authors: AD
authors: Kashuba
authors: HIV and STD Unit, Department of Infectious Diseases.
authors: Elena
authors: E
authors: Ferrer
authors: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors: Dan
authors: D
authors: Ouchi
authors: UNC Center for AIDS Research, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill.
authors: Craig
authors: C
authors: Sykes
authors: HIV and STD Unit, Department of Infectious Diseases.
authors: Nerea
authors: N
authors: Rozas
authors: HIV and STD Unit, Department of Infectious Diseases.
authors: Laura
authors: L
authors: Acerete
authors: HIV and STD Unit, Department of Infectious Diseases.
authors: Jordi
authors: J
authors: Curto
authors: HIV and STD Unit, Department of Infectious Diseases.
authors: Antonia
authors: A
authors: Vila
authors: HIV and STD Unit, Department of Infectious Diseases.
authors: Daniel
authors: D
authors: Podzamczer
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D015224:Dideoxynucleosides / Q000008:administration & dosage; D004338:Drug Combinations; D015658:HIV Infections / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D010865:Pilot Projects; D010879:Piperazines; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D011728:Pyridones; D020871:RNA Stability; D012367:RNA, Viral / Q000378:metabolism*; D012661:Semen / Q000737:chemistry* / Q000821:virology*; D013997:Time Factors; D055815:Young Adult; D000099226:Dolutegravir; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D004338:Drug Combinations; D006575:Heterocyclic Compounds, 3-Ring; D019259:Lamivudine; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012367:RNA, Viral; D000099226:Dolutegravir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir
keywords: HIV-1; antiretroviral therapy; dolutegravir; male genital tract, HIV reservoirs; semen