Ebola Virus Persistence Beyond Acute Infection: Could HIV-Associated Immune Dysfunction Influence Survivor Biology?

Ebola virus disease (EVD) has traditionally been considered an acute infection characterized by high mortality and severe systemic inflammation. However, growing evidence accumulated over the last decade has progressively challenged this view, demonstrating that Ebola virus may persist long after apparent clinical recovery within immune-privileged anatomical compartments, including the male genital tract, ocular tissues, central nervous system, and breast milk. Persistent viral reservoirs have been associated with prolonged RNA shedding, sexual transmission, recrudescence phenomena, and outbreak resurgence, highlighting the clinical and public health relevance of post-acute Ebola persistence. At the same time, increasing evidence suggests that EVD survivors frequently exhibit chronic inflammatory activation and long-lasting immune dysfunction. Persistent alterations involving cytokine signaling, T-cell responses, and antiviral immune regulation may contribute to incomplete viral clearance and reservoir maintenance. In this context, the potential interaction between Ebola virus persistence and HIV-associated immune dysregulation remains poorly explored despite the substantial geographical overlap between both infections in sub-Saharan Africa. This narrative review examines current evidence regarding Ebola virus persistence, immune-privileged reservoirs, survivor immune dysfunction, and persistence-associated transmission. Additionally, we discuss the biological plausibility that chronic immune activation, T-cell exhaustion, and impaired antiviral surveillance observed in people living with HIV (PWH) could theoretically influence persistence dynamics and long-term reservoir biology. Understanding these interactions may have implications for survivor monitoring, outbreak preparedness, and future research on post-acute viral reservoir diseases. Importantly, this review does not argue that HIV has been clinically established as a modifier of Ebola virus persistence. Rather, it examines Ebola virus persistence as an established post-acute phenomenon and considers whether HIV-associated immune dysregulation in people living with HIV (PWH) may represent a biologically plausible, but still untested, determinant of viral clearance and reservoir biology.