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By Constancia Mavodza, Sexual and Reproductive Health and Rights (SRHR) Research Analyst, Global Health Corps Fellow at the Centre for Health and Gender Equity (CHANGE) and Kate Segal, SRHR Policy Analyst, Global Health Corps Fellow at CHANGE.

An exciting emerging research canon that identifies links between vaginal bacteria and HIV underscores the need to prioritize women’s participation in HIV vaccine research. Because HIV passes through the vaginal lining and the female genital tract has a larger surface area than male genitalia, women face greater risk of HIV transmission from heterosexual vaginal intercourse.

But getting women in the door for clinical trials is difficult. Building trust with researchers and providers as well as structural disadvantages and societal barriers inhibit their participation in particular ways. For effective HIV prevention methods and an eventual vaccine, it is particularly important to recruit a diverse group of women – including pregnant women – for HIV vaccine clinical trials. Women’s inclusion in HIV vaccine research recognizes the unique biological factors that increase their HIV risk and ensures that women will receive evidence-informed care.

Adolescent girls and young women aged 15-24 comprise 60 percent of youth living with HIV globally, and in sub-Saharan Africa, adolescent girls and young women account for 74 percent of new HIV infections among youth. Discussions around risk reduction for this group have largely centered on behavioral indicators of adolescent girls and young women, such as having intergenerational sex. While certain behaviors can put girls and women at greater risk of HIV, focusing solely on social and behavioral drivers can veer into moral policing of sexual proclivities that is acutely gendered, particularly because some women cannot negotiate condom use and/or monogamy.

Physiological composition and biological mechanisms in HIV infection are different for men and women. For instance, there are sex-specific differences in HIV viral loads and CD4 counts, as well as in adverse responses to antiretroviral therapy. For adolescent girls, inflammation of the genitalia and greater presence of mucus in the immature cervix increase their vulnerability.

Another biological factor that makes women distinctively susceptible to HIV acquisition is the vaginal microbiome. The vaginal microbiome, or bacterial communities in the vagina, has been found to both increase and decrease HIV risk, depending on a woman’s bacterial makeup.

A recent study of six Eastern and Southern African countries identified seven types of vaginal bacteria that, when highly concentrated, are associated with increased vulnerability to HIV acquisition. It also found that women who acquired HIV had more diversity of bacteria in the microbiome. These findings were consistent for pregnant and post-partum women, female sex workers, and women in serodiscordant relationships (where only one partner is living with HIV).

The vaginal microbiome has also been found to impact the efficacy of antiretroviral drugs for HIV prevention. Results from a clinical trial of one microbicide found that for women whose microbiomes have a high prevalence of one particular bacteria, Lactobacillus, the medicine had significantly higher efficacy than for women in whom this bacteria is not dominant. Relatedly, women with a higher presence of Lactobacillus bacteria were associated with a lower risk of HIV infection.

What’s more, this study found regional differences in women’s vaginal bacteria concentrations: 90 percent of white women in developed countries had Lactobacillus-dominant microbiomes, compared with the majority of women from South Africa, who exhibited low Lactobacillus presence. That geography can be a determinant of your HIV risk indicates that behavioral and social factors can only explain so much, and including a diverse group of women — with diverse microbiomes — in clinical research is key to developing an effective vaccine that is suited to all populations.

Biological changes that happen during pregnancy may also heighten women’s vulnerability to HIV. Two studies found that for African HIV-negative women that are pregnant and in sexual relationships with men living with HIV, the risk of HIV transmission per sex act increased throughout pregnancy, and was highest during the six-month post-partum period. Relative to risk of HIV acquisition when not pregnant, which is approximately five percent, the studies found that the risk of infection was 2.91 times higher during the first trimester, 2.97 times higher during the second two trimesters, and 4.18 times higher post-partum. A biological mechanism called vaginal thinning, which takes place throughout pregnancy, could be the reason pregnant and post-partum women are more susceptible to HIV.

We have an opportunity to acknowledge the diversity of women’s bodies in HIV vaccine research and come up with solutions that are reflective of this complexity. Evidence that the vaginal microbiome and vaginal thinning affect women’s chances of acquiring HIV and response to HIV prevention drugs rightfully disrupts harmful narratives that concentrate too heavily on women’s sexual behavior.

Without accounting for women and the incredible variation in vaginal microbiomes, an effective HIV vaccine will remain out of reach. HIV clinical trials must include women to understand the factors that put particular groups at greater risk of HIV.

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