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. 2017 Feb 21;4(2):ofx033.
doi: 10.1093/ofid/ofx033. eCollection 2017 Spring.

Clinical and Mucosal Immune Correlates of HIV-1 Semen Levels in Antiretroviral-Naive Men

Brendan J W Osborne  1   2 , Angie K Marsh  1   2 , Sanja Huibner  1   2 , Kamnoosh Shahabi  1   2 , Cindy Liu  3   4 , Tania Contente  3 , Nico J D Nagelkerke  5 , Colin Kovacs  6 , Erika Benko  6 , Lance Price  3   4 , Kelly S MacDonald  1   2   7 , Rupert Kaul  1   2
Affiliations

Clinical and Mucosal Immune Correlates of HIV-1 Semen Levels in Antiretroviral-Naive Men

Brendan J W Osborne et al. Open Forum Infect Dis. .

Abstract

Background: This study was done to characterize parameters associated with semen human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) viral load (VL) variability in HIV-infected, therapy-naive men.

Methods: Paired blood and semen samples were collected from 30 HIV-infected, therapy-naive men who have sex with men, and 13 participants were observed longitudinally for up to 1 year. Human immunodeficiency virus RNA, bacterial load by 16S RNA, herpesvirus (Epstein-Barr virus and cytomegalovirus [CMV]) shedding, and semen cytokines/chemokines were quantified, and semen T-cell subsets were assessed by multiparameter flow cytometry.

Results: Semen HIV RNA was detected at 93% of visits, with >50% of men shedding high levels of virus (defined as >5000 copies/mL). In the baseline cross-sectional analysis, an increased semen HIV VL correlated with local CMV reactivation, the semen bacterial load, and semen inflammatory cytokines, particularly interleukin (IL)-8. T cells in semen were more activated than blood, and there was an increased frequency of Th17 cells and γδ-T-cells. Subsequent prospective analysis demonstrated striking interindividual variability in HIV and CMV shedding patterns, and only semen IL-8 levels and the blood VL were independently associated with semen HIV levels.

Conclusions: Several clinical and immune parameters were associated with increased HIV semen levels in antiretroviral therapy-naive men, with induction of local proinflammatory cytokines potentially acting as a common pathway.

Keywords: HIV; cytokines; herpesviruses; microbiome; semen..

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Figures

Figure 1.
Figure 1.
Association of semen human immunodeficiency virus (HIV) viral load with local inflammation and proinflammatory cytokines. Levels of semen HIV RNA in antiretroviral therapy-naive men were strongly associated with both the presence/absence of semen inflammation (top panel), based on modification of a previously defined mucosal algorithm, and with levels of individual proinflammatory cytokines (bottom 2 panels; interleukin [IL]-8 and IL-1β shown).
Figure 2.
Figure 2.
Reactivation of semen herepesviruses and the semen HIV viral load. Semen HIV RNA levels in ARV-Naive men were associated with levels of (A) semen CMV DNA (left) but not (B) semen EBV DNA (right).
Figure 3.
Figure 3.
Association of 16s rRNA bacterial load with semen HIV-1 RNA levels. The total concentration of bacterial 16s rRNA, a crude marker of the semen microbiome, was positively correlated with semen HIV RNA levels in antiretroviral therapy-naive men.
Figure 4.
Figure 4.
Longitudinal patterns of HIV RNA semen shedding over time in antiretroviral therapy-naive men. Examples of semen HIV RNA semen shedding patterns over time: (a) blood viral load (VL) consistently higher than semen; (b) persistently undetectable semen HIV RNA VL; (c) sustained disproportionate HIV semen shedding; (d) intermittent disproportionate HIV semen shedding. blood plasma; semen plasma.
Figure 5.
Figure 5.
Association of semen interleukin (IL)-8 level with the relative abundance of HIV RNA in semen versus blood. Semen levels of the proinflammatory cytokine IL-8 were strongly correlated with relative increases in semen versus blood HIV RNA in antiretroviral therapy-naive men (random intercept linear mixed model).
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