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. 2013 Jan 2;27(1):39-47.
doi: 10.1097/QAD.0b013e3283573305.

Herpes viruses and HIV-1 drug resistance mutations influence the virologic and immunologic milieu of the male genital tract

Sara Gianella  1 , Sheldon R Morris, Christy Anderson, Celsa A Spina, Milenka V Vargas, Jason A Young, Douglas D Richman, Susan J Little, Davey M Smith
Affiliations

Herpes viruses and HIV-1 drug resistance mutations influence the virologic and immunologic milieu of the male genital tract

Sara Gianella et al. AIDS. .

Abstract

Objectives: To further understand the role that chronic viral infections of the male genital tract play on HIV-1 dynamics and replication.

Design: Retrospective, observational study including 236 paired semen and blood samples collected from 115 recently HIV-1 infected antiretroviral naive men who have sex with men.

Methods: In this study, we evaluated the association of seminal HIV-1 shedding to coinfections with seven herpes viruses, blood plasma HIV-1 RNA levels, CD4 T-cell counts, presence of transmitted drug resistance mutations (DRMs) in HIV-1 pol, participants' age and stage of HIV-infection using multivariate generalized estimating equation methods. Associations between herpes virus shedding, seminal HIV-1 levels, number and immune activation of seminal T-cells was also investigated (Mann-Whitney).

Results: Seminal herpes virus shedding was observed in 75.7% of individuals. Blood HIV-1 RNA levels (P < 0.01) and seminal cytomegalovirus (CMV) and human herpes virus (HHV)-8 levels (P < 0.05) were independent predictors of detectable seminal HIV-1 RNA; higher seminal HIV-1 levels were associated with CMV and Epstein-Barr virus (EBV) seminal shedding, and absence of DRM (P < 0.05). CMV and EBV seminal shedding was associated with higher number of seminal T-lymphocytes, but only presence of seminal CMV DNA was associated with increased immune activation of T-lymphocytes in semen and blood.

Conclusion: Despite high median CD4 T-cells numbers, we found a high frequency of herpes viruses seminal shedding in our cohort. Shedding of CMV, EBV and HHV-8 and absence of DRM were associated with increased frequency of HIV-1 shedding and/or higher levels of HIV-1 RNA in semen, which are likely important cofactors for HIV-1 transmission.

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Conflict of interest statement

Conflicts of interest

Competing Interests: SG and MVV do not have any commercial or other associations that might pose a conflict of interest. DDR has served as a consultant for Bristol-Myers Squibb, Gilead Sciences, Merck & Co, Monogram Biosciences, Biota, Chimerix, Tobira, and Gen-Probe. DMS has received grant support from ViiV Pharmaceuticals and consultant fees from Gen-Probe.

Figures

Fig. 1
Fig. 1. Viral frequencies in semen for each HIV-1 infected subject(n=115)
Frequency (%) of patients(n = 115) having at least one semen sample positive for any herpesvirusDNA and for each individual tested virus separately.
Fig. 2
Fig. 2. Comparison of HIV-1 RNA levels in semen samples with or without detectable CMV and EBV DNA and presence of transmitted drug resistance mutations
(a) Seminal HIV-1 RNA levels compared between samples with and without detectable CMV DNA (Mann Whitney, p = 0.05), boxplots display whiskers with min and max values. (b) Seminal HIV-1 RNA levels compared between sample with and without detectable EBV DNA (Mann Whitney, p < 0.01), boxplots display whiskers with min and max values. (c) Seminal HIV-1 RNA levels compared between samples with and without transmitted drug resistance mutations (DRM) (Mann Whitney, p = 0.02), boxplots display whiskers with min and max values
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