HIV-1-RNA decay and dolutegravir concentrations in semen of patients starting a first antiretroviral regimen

Arkaitz Imaz, Javier Martinez-Picado, Jordi Niubó, Angela D.M. Kashuba, Elena Ferrer, Dan Ouchi, Craig Sykes, Nerea Rozas, Laura Acerete, Jordi Curto, Antonia Vila, Daniel Podzamczer

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    13 Citations (Scopus)

    Abstract

    © 2016 The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. Background. 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. Methods. 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. Results. 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. Conclusions. DTG concentrations in SP are sufficient to contribute to rapid seminal HIV-1 RNA suppression.
    Original languageEnglish
    Pages (from-to)1512-1519
    JournalJournal of Infectious Diseases
    Volume214
    Issue number10
    DOIs
    Publication statusPublished - 15 Nov 2016

    Keywords

    • antiretroviral therapy
    • dolutegravir
    • HIV-1
    • male genital tract, HIV reservoirs
    • semen

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