Epstein–Barr and cytomegalovirus DNA salivary shedding correlate with long‐term plasma HIV RNA detection in HIV‐infected men who have sex with men

Abstract

The aim of the study was to evaluate cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA salivary shedding in HIV-positive men who have sex with men (MSM) and to determine whether viro-immunological parameters and long-term (24 months) plasma HIV RNA (pHIV) detection may predict herpesviruses replication. A total of 193 HIV-positive MSM were consecutively recruited (mean CD4+ cell count 607 cells/mm(3) and mean nadir value 333 cells/mm(3) ); pHIV was analyzed for 24 months prior to saliva sampling: patients were categorized as successfully suppressed (SS) and not suppressed (NS). The EBV viral load was categorized as high viral load (HVL), intermediate (IVL), or low (LVL), CMV DNA as positive or negative. NS patients experienced both herpesviruses detectability more frequently respect to SS patients (P = 0.034); conversely, no salivary shedding was more frequent in SS patients (P = 0.014). HVL EBV was more frequent in NS patients than in SS subjects (P = 0.038 for isolated EBV detection and P = 0.001 when CMV shedding was associated). NS subjects with HVL EBV had a median pHIV of 43,820 copies/ml, significantly higher respect to IVL and LVL patients (P = 0.027 and P = 0.0005, respectively). CMV shedding was mostly associated to EBV shedding. NS patients showed a significantly higher frequency of saliva HVL EBV detection compared to SS patients; moreover, NS patients with HVL EBV had a higher pHIV respect to those with IVL and LVL shedding. Our results suggest that a successful pHIV suppression could reduce the burden of salivary EBV replication and likely the risk of herpesviruses-related cancers.

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

“…The most frequent virological pattern detected in the same patients at both T0 and T1 was the isolated EBV DNA shedding, with a comparable frequency in SSPs and in DV; this result is in accord with our previous data [20]. EBV persists as a latent infection of a memory B cell population, and these cells recirculate between the blood and the lymphoid tissues; lytic infection in the oropharyngeal epithelium leads to oral shedding when reactivation occurs [33], whereas CMV persists as a latent infection of the myeloid lineage, and it can reactivate to lytic infection at various sites [34].…”

“…Herpesvirus salivary shedding was not identified in 9 patients (9.8%, 7 SSPs and 2 PSPs); this last percentage is in accord with that reported in previous studies with a single herpesvirus salivary testing, ranging from 3 to 25% [17, 18, 20]. Conversely, we demonstrated multiple herpesvirus reactivations both at T0 and at T1 in 24 patients (26.1% of the overall study population).…”

“…Only a few studies have evaluated CMV DNA, EBV DNA and HHV-8 DNA simultaneously in salivary samples of HIV patients: one study had a cross-sectional design [16], one was a case-control study [17], one reported a comparative analysis between the results obtained in HIV-positive subjects and age- and sex-matched HIV seronegative controls [18], and Jacobson et al [19] performed a small pilot study that analysed 2–4 saliva specimens obtained from a prospective observational study spanning a 6–12 month period. In our previous study [20], which included 193 HIV-positive MSM, we showed that 76.2% of the entire cohort displayed detectable EBV DNA in their saliva. Additionally, CMV DNA was found in 18.7% of the subjects, and a double herpesvirus positivity was reported in 16.6% of the patients.…”

Oral and anal high-risk human papilloma virus infection in HIV-positive men who have sex with men over a 24-month longitudinal study: complexity and vaccine implications

“…The breakdown of the mucosal epithelial barrier by HIV may explain this association: Nazli et al [28] demonstrated that exposure to HIV-1 led to an upregulation of inflammatory cytokine production and to a significant decrease in tight junction protein expression and increased permeability while Tugizov et al [29] showed that tight junction disruption of the oral and anal epithelium due to the expression of the HIV tat and gp120 increased HPV pseudovirion paracellular penetration into the epithelium. However, we cannot exclude an independent role for immune-activation, as described for the interplay between HIV and CMV, EBV, and HHV-8 [30, 31].…”

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

“…Our study confirms previous findings of asymptomatic herpesvirus replication in HIV-infected individuals who are suppressed on ART. [24, 41, 42] Although there was only a modest trend for higher mean shedding rates among HIV(+) participants compared to age-matched HIV(−) MSM, there are some significant findings among the HIV(+) group that will have important implications in further studies on HIV-herpesvirus co-infection. First, shedding rates at each of the four timepoints did not necessarily correlate with each other.…”