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Longitudinal Viral Dynamics in Semen During Early HIV Infection.

  • Author(s): Morris, Sheldon R
  • Zhao, Mitchell
  • Smith, Davey R
  • Vargas, Milenka V
  • Little, Susan J
  • Gianella, Sara
  • et al.
Abstract

Multiple viruses co-infect the male genital tract, influencing each other's replication and perhaps affecting HIV pathogenesis and disease progression.This study included 453 longitudinal seminal samples from 195 HIV-infected men from the San Diego Primary Infection Cohort and 67 seminal samples from HIV-negative healthy controls. Seminal HIV RNA and DNA from seven human herpesviruses (HHV) were measured by RT-PCR. Longitudinal shedding rates were determined by Kaplan-Meier survival analysis. Predictors of viral shedding were determined using backwards selection in a multivariable GEE model.HIV-infected participants present significantly increased rates of seminal HHV shedding compared to HIV-negative controls. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the most commonly detected HHV in semen of HIV-infected participants. Persistent shedding was more common for CMV and EBV when compared to other HHV. With exception of HHV-7, HHV shedding was not significantly influenced by HIV RNA levels, CD4+ counts or antiretroviral therapy. Presence of CMV, EBV and Herpes Simplex Viruses (HSV) were independent predictors of genital HIV RNA shedding after adjusting for plasma HIV RNA and longitudinal measurements.Seminal replication of multiple HHV is common in our HIV primary infection cohort. Genital replication of CMV and EBV was the most common and was significantly associated with seminal HIV RNA shedding. Prevalence of HSV shedding was lower and mostly intermittent but its association with seminal HIV RNA was the strongest. Understanding the complex viral milieu in semen is important for HIV-transmission but might also play a role in HIV pathogenesis and disease progression.

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