Inflammation and HIV Transmission in Sub-Saharan Africa

Abstract

While the per-contact risk of sexual HIV transmission is relatively low, it is fourfold higher in sub-Saharan Africa, and this may partly explain the major global disparities that exist in HIV prevalence. Genital immune parameters are key determinants of HIV transmission risk, including epithelial integrity and the presence of highly HIV-susceptible intraepithelial or submucosal CD4+ T cell target cells. Biological parameters that may enhance mucosal HIV susceptibility in highly HIV-affected regions of sub-Saharan Africa include increased levels of mucosal inflammation, which can affect both epithelial integrity and target cell availability, as well as the increased mucosal surface area that is afforded by an intact foreskin, contraceptive choices, and intravaginal practices. There are multifactorial causes for increased mucosal inflammation, with the prevalence and nature of common co-infections being particularly relevant.

Distinct Effects of the Cervicovaginal Microbiota and Herpes Simplex Type 2 Infection on Female Genital Tract Immunology

“…The preexisting mucosal immune milieu at the site of sexual HIV exposure is a key determinant of HIV acquisition risk, with relative immune quiescence being associated with reduced risk and genital inflammation with enhanced HIV susceptibility [34]. Mucosal inflammation may increase HIV risk in at least 2 ways.…”

Southern Africa: the Highest Priority Region for HIV Prevention and Care Interventions

“…Kaul et al highlight the role of genital and systemic inflammation in increasing risk of sexual acquisition of HIV [9]. His immunological focus presents numerous opportunities for intervention in the vaginal microbiome and systemic immune system.…”

“…Observations of transmission risk correlating with plasma and genital viral load have translated into HPTN 052 clinical trial evidence of efficacy of ART in the infected partner preventing transmission to the HIV-uninfected partner [•9,•25,28-31]. Shanaube and Bock highlight how TasP has increased focus on the need to provide access to medications in a timely manner without treatment interruption due to drug stockouts, services to enhance access to testing and retention in care, and attention to highly vulnerable key populations, including adolescent and young women, persons in serodiscordant relationships, men who have sex with men (MSM), sex workers, and people who inject drugs (PWID) [23].…”

“…From varying perspectives, biological, policy, and epidemiologic, Kaul et al, Simelela et al, and Shanaube and Bock all discuss the role that HIV counseling and testing (HCT) and voluntary medical male circumcision (VMMC) play in prevention [•3,•9,•25]. Kaul et al provides insight into the decreased likelihood of transmission for HIV seropositive persons on ART and the increased likelihood of infection for HIV seronegative persons with specific intravaginal practices or presence of genital co-infections [•9].…”

“…Kaul et al provides insight into the decreased likelihood of transmission for HIV seropositive persons on ART and the increased likelihood of infection for HIV seronegative persons with specific intravaginal practices or presence of genital co-infections [•9]. While the control of sexually transmitted infections (STI) alone may not be a robust HIV control strategy when implemented in isolation of other efforts, no one can dispute the co-factor role that Kaul et al highlight, and the importance of STI control as a good unto itself, and an adjunct to the overall HIV control efforts [•9]. …”