The most common bacterial community in the genital tract of healthy South African women is associated with a more than four-fold increase in the risk of acquiring HIV, found researchers from the Massachusetts General Hospital (MGH) and the Ragon Institute of MGH, Massachusetts Institute of Technology (MIT) and Harvard. In the research, the investigators report that women with specific high-risk vaginal bacterial communities not only acquired HIV at higher rates but also had increased inflammation and a greater number of HIV target cells in their reproductive tract.
“Higher numbers of HIV target cells at the initial site of exposure has been shown to increase the risk of infection and thus constitutes a likely biological mechanism for the observed increase in HIV risk,” says Dr Douglas Kwon, of the Ragon Institute and the MGH division of infectious diseases, senior author of the report.
The study enrolled 236 HIV-uninfected young black women participating in a poverty alleviation program in Umlazi, South Africa, who were followed for an average of 336 days. Using advanced methods to sequence the vaginal microbiome, the investigators found that almost 60% of women had highly diverse bacterial communities while the minority had the type of Lactobacillus-dominant bacterial population typically seen in healthy white women in developed countries.
Based on this information, the researchers grouped the genital samples they studied into four community types – referred to as “cervicotypes” – two of which were characterised by highly diverse, low- Lactobacillus bacterial populations. They then monitored HIV infection rates within these groups during the following year and found a four times greater incidence of HIV acquisition among women with diverse anaerobic bacterial communities, compared to those with Lactobacillus-dominant microbiomes. This increased risk was independent of other factors, including the presence of sexually transmitted infections, the use of condoms, and sexual behaviour.
The investigators further identified specific bacterial species associated with increased or reduced HIV acquisition risk and showed that introducing high-risk bacteria into the vaginas of mice increased numbers of the activated CD4 T cells that are the virus’s primary target, establishing a direct link between the high-risk bacteria and a known biological marker of HIV susceptibility.
“Our findings demonstrate the importance of considering the genital microbiome in the development of new strategies to reduce HIV acquisition in women living in sub-Saharan Africa,” says lead author Dr Christina Gosmann, of the Ragon Institute. “By identifying both bacterial communities and individual bacterial species associated with HIV risk, we can provide specific targets for the development of preventive strategies. In addition, treatments targeting genital bacteria could improve the effectiveness of existing preventive measures.”
Kwon adds: “Understanding the impact of differences in the genital microbial population could also have important implications for pregnant women and their infants. Some of the risk-associated pro-inflammatory bacteria that we found in our study may also contribute to poor reproductive outcomes, such as premature birth and other complications of pregnancy.”
The research team is now investigating how to leverage the genital microbiome to reduce HIV risk and improve the efficacy of existing preventative measures.
Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genital bacterial communities dominated by anaerobes other than Gardnerella were at over 4-fold higher risk of acquiring HIV and had increased numbers of activated mucosal CD4+ T cells compared to those with Lactobacillus crispatus-dominant communities. We identified specific bacterial taxa linked with reduced (L. crispatus) or elevated (Prevotella, Sneathia, and other anaerobes) inflammation and HIV infection and found that high-risk bacteria increased numbers of activated genital CD4+ T cells in a murine model. Our results suggest that highly prevalent genital bacteria increase HIV risk by inducing mucosal HIV target cells. These findings might be leveraged to reduce HIV acquisition in women living in sub-Saharan Africa.
Christina Gosmann, Melis N Anahtar, Scott A Handley, Mara Farcasanu, Galeb Abu-Ali, Brittany A Bowman, Nikita Padavattan, Chandni Desai, Lindsay Droit, Amber Moodley, Mary Dong, Yuezhou Chen, Nasreen Ismail, Thumbi Ndung’u, Musie S Ghebremichael, Duane R Wesemann, Caroline Mitchell, Krista L Dong, Curtis Huttenhower, Bruce D Walker, Herbert W Virgin, Douglas S Kwon