HIV/HSV-2 Syndemic

HIV and HSV are two viral infections that represent a substantial global health burden, with an estimated 3.7 billion individuals infected with HSV-1, 417 million with HSV-2, and 36.7 million with HIV. In sub-Saharan Africa, the site of over 2/3 of HIV infections (and the highest prevalence of HSV-2), it has been suggested that HSV-2 has played a more significant role than any other biological or behavioral factor in fueling the HIV epidemic. Epidemiological studies have constituently shown that HSV seropositivity increases the risk of acquiring HIV, and that HIV/HSV-2 dually infected individuals have an increased risk of transmitting HIV to their partner(s). HIV/HSV-2 dually infected individuals have also been shown to have higher HIV plasma viral loads (PVL) than individuals infected with HIV alone.

Given the lifelong nature of infection with HSV-2 and HIV, the debilitating disease they can cause, and the substantial public health burden they present, understanding the mechanisms behind infection with these pathogens, and the interplay between them, represents an important avenue of inquiry. While a significant effort has been given to answering these questions, most studies to date have focused on the local inflammatory response to HSV lesions. While these studies have helped our understanding of the increased risk of HIV acquisition associated with prior HSV infection, they do not address the systemic effects of HSV-2 on the course of HIV infection (for example, elevated HIV PVLs).

Recent work from our lab has demonstrated that HSV-2 has previously unappreciated impacts on systemic immunity that may help to explain previous epidemiological findings on the interactions between HSV-2 and HIV (Mesquita et al, 2016). We identified changes in CD4 T cells of HSV-2 infected individuals that indicate a generally more activated phenotype (relative to healthy controls). We are now working to characterize the mechanisms by which HSV-2 induces these changes, and to better understand their long-term consequences, including how they may impact the course of HIV infection.