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J Infect Dis. 2016 Nov 15;214(10):1512-1519. Epub 2016 Aug 30.

HIV-1-RNA Decay and Dolutegravir Concentrations in Semen of Patients Starting a First Antiretroviral Regimen.

Author information

1
HIV and STD Unit, Department of Infectious Diseases.
2
Institució Catalana de Recerca i Estudis Avançats, Barcelona.
3
University of Vic-Central University of Catalonia, Vic.
4
AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
5
Department of Microbiology, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat.
6
UNC Center for AIDS Research, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill.

Abstract

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.

KEYWORDS:

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

PMID:
27578849
PMCID:
PMC5091371
DOI:
10.1093/infdis/jiw406
[Indexed for MEDLINE]
Free PMC Article

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