Assessment of γ-herpesvirus infection dynamics in non-hospitalised people living with HIV during the COVID-19 pandemic in South Africa

Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are oncogenic human γ-herpesviruses highly prevalent in Sub-Saharan Africa. Both establish latent early-life infections, with intermittent lytic reactivations, often triggered by viral co-infections, particularly in immunocompromised individuals. In this retrospective observational cross-sectional sub-study, we leveraged a cohort of 407 non-hospitalised people living with HIV (PLWH) attending antiretroviral therapy services in South Africa during the COVID-19 pandemic, with previously reported increased reactivation of KSHV upon SARS-CoV-2 exposure, particularly in COVID-19 unvaccinated individuals (Lambarey et al., 2024). In contrast to the generally low KSHV viral loads (VL), we observed high detectability (97.0 %) of EBV DNA in the patients' peripheral blood, with 12.4 % of patients displaying elevated EBV VL of ≥1 × 10⁵ copies/10⁶ cells. However, neither SARS-CoV-2 exposure nor COVID-19 vaccination had an impact on EBV reactivation. Interestingly, patients with chronically elevated EBV VL had higher detectability of KSHV VL (35.0 %) compared to the remainder of the cohort with undetectable or <1 × 10⁵ copies/10⁶ cells EBV VL (18.8 %), which was confirmed by logistic regression identifying significantly higher odds of elevated EBV VL in patients with detectable KSHV VL (p = 0.03, adjusted OR 2.42 [95 % C.I. 1.10–5.33]). These results suggest an interplay between KSHV reactivation, possibly triggered by SARS-CoV-2 exposure, and chronically high EBV VL which should be closely monitored in the post-pandemic era, particularly in immunocompromised patients.