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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • California / epidemiology
  • Coinfection
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / immunology*
  • Drug Resistance, Viral / immunology*
  • Genitalia, Male / virology*
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Herpesviridae Infections / drug therapy
  • Herpesviridae Infections / immunology*
  • Homosexuality, Male
  • Humans
  • Male
  • Mutation
  • RNA, Viral
  • Retrospective Studies
  • Semen / virology*
  • Virus Shedding

Substances

  • RNA, Viral