TY - JOUR
T1 - Clinical and mucosal immune correlates of HIV-1 semen levels in antiretroviral-naive men
AU - Osborne, Brendan J.W.
AU - Marsh, Angie K.
AU - Huibner, Sanja
AU - Shahabi, Kamnoosh
AU - Liu, Cindy
AU - Contente, Tania
AU - Nagelkerke, Nico J.D.
AU - Kovacs, Colin
AU - Benko, Erika
AU - Price, Lance
AU - MacDonald, Kelly S.
AU - Kaul, Rupert
N1 - Publisher Copyright:
© The Author 2017.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Cytokines
KW - HIV
KW - Herpesviruses
KW - Microbiome
KW - Semen
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U2 - 10.1093/ofid/ofx033
DO - 10.1093/ofid/ofx033
M3 - Article
AN - SCOPUS:85031895157
SN - 2328-8957
VL - 4
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 2
M1 - ofx033
ER -