Introduction: The association of mucosal shedding of human simplex virus (HSV)-2, Kaposi’s sarcoma-associated herpesvirus (KSHV) and cytomegalovirus (CMV) after antiretroviral therapy (ART) initiation in women-living-with-HIV (WLWH) with systemic inflammation is unclear.

Methods: We recruited 187 ART-naive adult WLWH in south-central Uganda. HSV-1, HSV-2, CMV, and Varicella Zoster Virus (VZV) in vaginal secretions and Kaposi’s sarcoma-associated herpesvirus (KSHV) in oral swabs were quantified by PCR. Plasma biomarkers of systemic inflammation were measured by ELISA or electrochemiluminescence before and after ART initiation (weeks 8, 12, and 24).

Results: Participants had a baseline median age of 28 years and CD4 count of 413 cells/μL. Viral shedding rates were similar for all tested viruses between baseline and post-ART timepoints in the overall study population. CMV shedding significantly increased from a baseline rate of 53% to 77% at week 4 visit (P-value = .016), and 73% at week 8 visit (P-value = .027) in participants with a baseline CD4 count ≤200 cells/µL. CRP, TNFα, and TNFR1 levels associated with CMV shedding at week 8, IL-6 associated with HSV-2 shedding at week 4, while sCD14 and TNFR1 associated with HSV-2 shedding at week 8. Also, CRP and IL-27 were associated with KSHV shedding at week 4 and week 8, respectively.

Conclusions: Although ART initiation was not associated with increased herpesvirus shedding overall, CMV shedding increased in women with advanced HIV-1. The association of mucosal shedding of CMV, HSV-2, and KSHV in post-ART timepoints with different baseline biomarkers of systemic inflammation suggest that distinct immunological functions are implicated in the control of their viral replication.