An unorthodox area of inquiry on HIV prevention is emerging from research led by African scientists based in Durban, South Africa. The research looks into the viability of healthy bacteria in the vagina in influencing a woman’s vulnerability to HIV infection.

Women continue to bear the burden of the global HIV epidemic, with the latest 2026 UNAIDS data showing that they account for 53% of all people living with HIV worldwide. Sub-Saharan Africa accounts for a major share of this number, with women and girls making up about 63% of new infections in the region, which translates to nearly 3 out of every 5 new HIV infections reported.

Despite decades of scientific progress, from antiretroviral medicines, commonly known as ARVs, that suppress the virus to long-acting prevention tools that reduce the risk of infection, it has become apparent that addressing this challenge requires more than developing new medicines. It also requires investing in African scientists who can ask new questions, build evidence from local contexts, and design innovative approaches to prevention.

One such question has driven scientists from the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) consortia, led by Professor Thumbi Ndung'u, a Kenyan Immunologist and Virologist, based at the Africa Health Research Institute (AHRI) in Durban, South Africa, to investigate whether these communities of bacteria that live in the vagina, could influence a woman's vulnerability to HIV infection.

Their research suggests that some vaginal bacteria may help create an environment that makes it more difficult for HIV to establish infection.

Understanding the vaginal ecosystem

The vagina is home to a complex community of microorganisms known as the vaginal microbiome. Like the microbes found in the gut that aid in proper digestion and metabolism, vaginal bacteria interact with the body, helping maintain a balanced environment and supporting natural defence mechanisms.

One good bacterial species in the vaginal microbiome stands out; "Lactobacillus crispatus is the bacteria you want in the female genital tract," says Prof. Thumbi," those are the bacteria associated with a healthy vagina."

Lactobacillus crispatus is a friendly bacteria, commonly referred to as a probiotic that can be found as an added ingredient in some fermented everyday food products we consume such as kimchi, fermented pickles and specific yogurt brands. Foods that also boost the natural growth of the bacteria in the vagina, also known as prebiotics include, onions, bananas and high vegetable and fish diets.

When Lactobacillus crispatus dominates, it helps maintain an acidic environment that discourages harmful organisms from thriving. However, when this balance is disrupted and replaced by a wider variety of bacteria, a condition often associated with bacterial vaginosis, the protective environment may change.

The questions the researchers are asking is whether this disruption could also influence HIV risk.

Following women before infection happens

To explore this possibility, the SANTHE team established a closely monitored cohort of young women at high risk of HIV acquisition in Durban, South Africa, known as the Females Rising through Education, Support, and Health (FRESH) cohort. Building and sustaining such research requires more than individual scientific expertise. It depends on long-term investment in research networks, infrastructure, trained researchers, and partnerships that allow scientists to follow complex health questions over time. Through the DELTAS Africa programme, African research institutions have been strengthened to pursue globally relevant scientific questions while addressing health challenges that affect communities across the continent.

Participants in the FRESH study were HIV-negative when they joined the research and were supported through job training and health education. They visited clinics twice every week for HIV testing, while researchers collected blood and vaginal samples over time. This intensive follow-up allowed scientists to capture HIV infection at its earliest stages and compare women who acquired HIV with those who remained HIV-free.

"We were able to ask the question," says Prof. Thumbi, "what distinguishes those who acquire HIV infection from those who don't?"

The answer pointed towards the vaginal microbiome. Women whose microbiomes were dominated by Lactobacillus crispatus were the least likely to acquire HIV. Those with more diverse bacterial communities faced a substantially higher risk. The observation raised a deeper question: why?

Why beneficial bacteria matter

Researchers found that women with healthier Lactobacillus crispatus-dominated microbiomes also had lower levels of inflammation in the genital tract. Rather than directly attacking HIV, beneficial bacteria appeared to influence the surrounding environment, making it less favourable for infection to take hold.

The next challenge was determining whether scientists could deliberately restore a protective vaginal microbiome in women whose bacterial balance had been disrupted by bacterial vaginosis.

The team designed a clinical trial that first treated bacterial vaginosis using metronidazole, a prescription antibiotic. Participants then received either a vaginal preparation containing Lactobacillus crispatus or a placebo (a fake treatment that has no real medicine in it).

The findings offered cautious optimism, four weeks after treatment, around 40% of women who received the beneficial bacteria successfully established Lactobacillus crispatus in their vaginal microbiome. None of the women who received a placebo achieved this outcome.

However, by eight weeks, the effect had begun to decline, with successful colonisation falling to around one quarter of participants. The findings showed that modifying the vaginal microbiome is possible but also highlighted the complexity of sustaining these changes.

Beyond HIV prevention

The implications of this research extend beyond HIV, where disrupted vaginal microbiomes are also associated with bacterial vaginosis, preterm birth and HPV-associated cervical disease. Restoring a healthier microbial balance could therefore contribute to broader improvements in women's reproductive health.

Although more research is needed before microbiome-based interventions become part of routine healthcare, the work is already changing how scientists think about HIV prevention. The research highlights what can emerge when African scientists are empowered to pursue ambitious questions through strong research networks and sustained investment.

DELTAS Africa, implemented by SFA Foundation and supported by Wellcome and FCDO UK, seeks to amplify the development of African world-class researchers and scientific leaders on the continent, while strengthening African institutions. We support researchers in addressing Africa’s most pressing health, climate and agriculture challenges. This is through improving the research environment, funding and training scientists and fostering equitable collaborations and societal engagement of researchers.