Microbial functional properties that modulate inflammation and HIV risk in African women

HIV remains among the world’s most serious healthcare challenges, with 1.7 million new infections in 2019 alone. Sub-Saharan Africa is the epicentre of the HIV epidemic, where approximately 61% of new HIV infections occur annually. Young women, in particular, account for the large majority of incident infections in this region. We have shown previously that female reproductive tract (FRT) inflammation is associated with high risk of acquiring HIV and some forms of pre-exposure prophylaxis (PrEP) lack efficacy in women with inflammation (Masson et al., Clinical Infectious Diseases, 2015; McKinnon et al., Nature Medicine, 2018). While the drivers of this inflammation have not been fully established, we have found that sexually transmitted infections (STIs) and non-optimal microbiota, which are highly prevalent in Africa, are associated with increased FRT pro-inflammatory cytokine concentrations (Masson et al., Sexually Transmitted Infections, 2014). On the other hand, some bacterial species (lactobacilli) are considered optimal and are able to regulate inflammatory responses in the FRT (Chetwin et al., Scientific Reports, 2019; Manhanzva et al., Scientific Reports, 2020). There are however major gaps in our understanding of the etiological causes of FRT inflammation and the mechanisms underlying the immunomodulatory properties of the vaginal microbiota and increased HIV risk. This study will use cutting-edge “omics” approaches to characterize the immunomodulatory properties of the FRT microbiota. Clinical samples from high risk African women will be utilised to isolate both optimal and non-optimal bacterial species and define their functions and activities that influence inflammatory responses. This research will establish a better understanding of the biological factors that modulate FRT inflammation and risk of HIV. This study could lead to the development of novel diagnostics and biotherapeutic products to treat non-optimal microbiota and FRT inflammation and reduce HIV acquisition risk.