Subclinical herpesvirus shedding among HIV-1-infected men on antiretroviral therapy

Abstract

Design We evaluated the subclinical shedding of 6 different herpesviruses in antiretroviral drug-treated HIV(+) men who have sex with men (MSM), and determined how this is associated with markers of inflammation and immune activation. Methods We obtained blood, semen, throat washing, urine, and stool from 15 antiretroviral-treated HIV-1-infected MSM with CD4+ T cell reconstitution, and 12 age-matched HIV(−) MSM from the Multicenter AIDS Cohort Study at 4 timepoints over 24 weeks to measure DNA levels of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 and 2, human herpesvirus 6 (HHV6), and HHV8. T cell activation and plasma levels of soluble markers of inflammation and activation were also measured at the corresponding timepoints. Results HIV(+) participants had a trend for higher total herpesvirus shedding rate. HIV(+) participants also had a significantly higher rate of shedding EBV and CMV compared to the HIV(−) group. Herpesvirus shedding was mostly seen in throat washings. In the HIV(+) group, herpesvirus shedding rate inversely correlated with plasma levels of interferon gamma-induced protein 10 (IP-10) and soluble CD163 (sCD163). CMV DNA levels negatively correlated with levels of T cell activation. There was a trend for a positive correlation between EBV shedding rate and plasma soluble CD14. HHV6 shedding rate negatively correlated with plasma levels of interleukin-6, sCD163, and IP-10. Correlations were not observed among HIV(−) individuals. Conclusions Among treated HIV-infected MSM, there are higher subclinical shedding rates of some herpesviruses that occurs in different body compartments and negatively correlates with levels of inflammation and immune activation.

HIV Co-infection Augments EBV-Induced Tumorigenesis in vivo

“…Even in healthy individuals, EBV periodically reactivates in the body which could stimulate local immune activation, potentially enhancing HIV replication (5). Studies in PLWH have attempted to evaluate associations between herpesvirus shedding (as determined by detectable virus in peripheral blood, throat washes, urine, stool, and/or semen) and HIV viral loads, however, given the high prevalence of other herpesviruses in PLWH, it is difficult to directly determine the effect of EBV on HIV replication and pathogenesis (25,26). Humanized mice could serve as a model to directly evaluate the effect of EBV infection on HIV replication, pathogenesis and latency in vivo.…”

Cytomegalovirus, Epstein-Barr virus and human herpesvirus 8 salivary shedding in HIV positive men who have sex with men with controlled and uncontrolled plasma HIV viremia: a 24-month longitudinal study

“…In addition to the physio-pathological explanation, the high frequency of shedding regardless of the virological response to ART could be related to the presence of immunoactivation, which was also demonstrated in patients with successful plasma HIV RNA suppression [35]. Agudelo Hernandez et al [36] reported that there was a trend of a positive correlation between the subclinical EBV DNA shedding rate (evaluated in different sites, included throat washings) and plasma levels of soluble CD14, which is a marker of monocyte activation, in HIV patients who have been virally suppressed on ART for a median of 7 years.…”

Epstein - Barr Virus Salivary Shedding in Patients with Acute Infectious Diseases: A Pilot Study

“…EBV reactivation identified by PCR testing in plasma has also been documented in patients in intensive care units ( 20 , 21 ), in patients with COVID-19 (22-24), long COVID-19 ( 19 ), malaria ( 25 ) and HIV ( 26 , 27 ).…”