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. 2016 Nov 15;214(10):1512-1519.
doi: 10.1093/infdis/jiw406. Epub 2016 Aug 30.

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

Arkaitz Imaz  1 , Javier Martinez-Picado  2   3   4 , Jordi Niubó  5 , Angela D M Kashuba  6 , Elena Ferrer  1 , Dan Ouchi  4 , Craig Sykes  6 , Nerea Rozas  1 , Laura Acerete  1 , Jordi Curto  1 , Antonia Vila  1 , Daniel Podzamczer  1
Affiliations

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

Arkaitz Imaz et al. J Infect Dis. .

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.

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Figures

Figure 1.
Figure 1.
Decline in human immunodeficiency virus (HIV) type 1 RNA decline through week 24; times points denote days (d) and weeks (wk) after baseline. A, Blood plasma. B, Seminal plasma.
Figure 2.
Figure 2.
Human immunodeficiency virus (HIV) type 1 RNA decay dynamics in blood plasma (BP) and seminal plasma (SP).
See this image and copyright information in PMC

Comment in

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