The Link Between Vaginal Bacteria And HIV Risk In South African Women

By Gabriella Meltzer

This past summer’s International AIDS Conference in Durban, South Africa, hosted by UNAIDS, represented monumental progress toward bringing about an “AIDS-free generation” by 2030. Sixteen years ago, the last time Durban hosted this conference, the global HIV/AIDS picture was far more bleak: 34.3 million people living with HIV/AIDS around the world, along with 5.4 million new infections and 2.8 million deaths in 1999 alone. At the time, South Africa’s government, led by former President Thabo Mbeki, was touting AIDS denialism; and his health minister, Manto Tshabalala-Msimang, was promoting a completely nonsensical combination of herbs and foods that would supposedly cure the disease. The South African government refused to provide treatment to HIV-positive individuals despite the fact that international pharmaceutical companies had finally capitulated in a years-long antiretroviral (ARV) pricing battle and agreed to provide the country with financial assistance to access life-saving drugs.

Today, South Africa has the largest operating antiretroviral treatment of any country, largely financed by domestic resources. Recent numbers illustrate marked improvements globally, proof of stalwart commitment on the part of the international community to tackle the pandemic. While 2015 saw 2.1 million new infections, 1.1 million AIDS-related deaths, and 36.7 million people living with HIV/AIDS worldwide, 17 million of the latter currently had access to life-saving ARV therapy.

Despite these strides, much work remains to be done — and nowhere is that clearer than in Durban. South Africa continues to be at the epicenter of the AIDS pandemic in spite of its rising economic growth; nearly one out of every five South African adults is HIV-positive. In 2015, 380,000 people in the country were newly infected with HIV, and there were 180,000 AIDS-related deaths. While many subpopulations are particularly vulnerable to contracting HIV, including gay men, intravenous drug users, and incarcerated individuals, in the developing world and South Africa specifically, young women represent a large number of new infections.

Countless studies show the undeniable link between gender inequality, intimate partner violence and subordination, poverty, and HIV status. Young women are often forced to drop out of primary or secondary school, where they do not receive sex education, to marry older men. This practice gives young women little agency in their own sexual, social, or economic health, as they are completely dependent upon often disloyal spouses and are not entitled to property ownership or the right to financial decision-making. Impoverished young women also cannot access adequate reproductive healthcare, either because there is a dearth of clinical resources in the area or because services are geared toward older women with children as a result of the stigma and discrimination surrounding adolescent sexual activity and HIV status.

Due to this confluence of factors, HIV/AIDS remains the number one killer of women of childbearing age worldwide, and South Africa is no exception. In South Africa, nearly 2,000 new HIV infections occur among young women and adolescent girls between the ages of 15 and 24 on a weekly basis, a rate two and a half times greater than the rate for their male counterparts. There are currently 600,000 young women and over 4 million over 15 years of age living with HIV, as compared to 210,000 young men and 2.7 million over the age of 15.

In many ways, KwaZulu-Natal, which sits on the eastern side of the country along the Indian Ocean, is the typical setting for a high incidence of HIV/AIDS in young women. It is one of South Africa’s most productive regions and is home to nearly 20% of its population. Durban, the seat of its municipality and host of the 2016 International AIDS Conference, is one of the fastest growing cities worldwide with one of the world’s top ten busiest harbors. The province prides itself on tourism, steel production, coal mining, meat processing, and mixed agriculture. This wealth, however, is not equitably distributed, as the percentage of those living below the food poverty line of R318 (or $23) per month increased from 25% to 28% of the population between 2010 and 2014, and there are 3.2 million extremely poor people out of a total population of 10.5 million.

That being said, can poverty and inequality alone explain KwaZulu-Natal’s alarmingly high HIV incidence rate of 6% among women and girls under 25, compared to roughly 1% incidence rates nationally? Probably not. So scientists from CAPRISA (Centre for the AIDS Programme of Research in South Africa) and universities throughout North America have turned to the vaginal microbiota to find out more.

Vaginal micro-biwhatta, you say?

You’ve probably heard a lot of buzz surrounding the microbiome in recent years. From obesity to cancer to Alzheimer’s, this new field of science could potentially hold the explanation and cure for some of human health’s most perplexing puzzles. But let’s take a step back.

In recent years, microbiologists have debunked nearly everything you learned about human physiology in high school biology. We were taught that the entire body is made up of cells, different kinds of which work together to build our organs, skeleton, and bones, and perform all our daily and life cycle functions. It turns out, however, that microbes such as bacteria, fungi, protozoa, and viruses outnumber the cells in our bodies ten to one. In fact, the number of genes in a person’s microbiome is 200 times that contained in the human genome. These tiny organisms do a whole lot of good, such as regulating our immune system, digesting our food, and producing many vitamins.

Autoimmune diseases such as Crohn’s and ulcerative colitis, rheumatoid arthritis, and MS are not passed down in family trees by genetic endowment, but through families’ unique microbiomes. When microbiomes go haywire, the proper balance of organisms goes off-kilter and disease-inducing microbes, known as pathogens, accumulate in the body, causing genes and metabolic activity to malfunction and attack the immune system, resulting in an inflammatory response. Inflammation of tissues, joints, and organs are the classic symptoms of autoimmune diseases; they are the body’s way of fighting off those pesky microorganisms.

The clusters of bacteria in individual parts of the body — such as the skin, mouth, gut, and yes, even vagina — are known as microbiota. So the fact that HIV is the human immunodeficiency virus might mean that the microbiome, and the vaginal microbiota in particular, hold the answer to KwaZulu-Natal’s mysteriously high incidence rates.

Two studies built upon previous clinical trials were presented at this year’s International AIDS Conference, revealing the influence of the vaginal microbiota on HIV incidence. In 2010, the CAPRISA team conducted a study in which they recruited 889 women in a study of the effectiveness of a vaginal gel containing the popular antiretroviral tenofovir. Of the 444 women who received the placebo gel, 60% heterosexually contracted HIV, versus 38% of those who received the gel containing the medication. Interpreting the results as statistically significant, scientists jubilantly announced, “It is the first time any biological intervention against HIV-1 transmission has ever shown convincing efficacy in a large trial,” and “It’s a clear-cut result with obvious protection at a meaningful level.” Yet researchers continued to wonder why the gel wasn’t more effective, and why it eventually failed in a follow-up trial conducted in 2011.

The first study presented at this year’s conference analyzed the vaginal microbiota of 119 women who were HIV-negative at the start of the 2010 trial, when scientists compared the 49 who had since become infected with HIV to the 70 who remained HIV-negative. This group of women had previously taken part in a study sponsored by Massachusetts General Hospital, MIT, and Harvard that showed certain bacterial species commonly found in South African women’s genital tracts induced inflammation, increasing their susceptibility to HIV infection. The Boston-based scientists demonstrated the linkage between decreases in Lactobacillus, a bacteria commonly found in yogurt, with a greater likelihood of vaginal inflammation. While they found that Lactobacillus was highly prevalent in 90% of American women’s vaginal microbiota, this was only the case for 37% of women hailing from KwaZulu-Natal.

The only problem? The conditions for Lactobacillus to do its vaginal bidding have to be just right, with a vaginal pH level below 4. That’s greater than the acidity of a pot of black coffee, and we all know what kind of havoc that can wreak on an empty stomach.

Salim Abdool Karim and Ian Lipkin of Columbia University’s Mailman School of Public Health built upon this previous work by trying to deduce the exact microbial recipe necessary to ward off attacking HIV viruses. Extracting thousands of bacteria ribosomal RNA, they found that women with levels greater than 1% of Prevotella bivia (a rare species of bacteria) along with low levels of Lactobacillus were thirteen times more likely than other women to contract HIV. P. bivia is associated with particularly high levels of lipopolysaccharide, a compound that lives on bacteria’s cell walls and promotes inflammatory activity. In other words, the vaginas of the women of KwaZulu-Natal were not only deficient in Lactobacillus, but also housed abnormally high amounts of P. bivia — the ideal environments for an HIV virus to penetrate and destroy a young woman’s immune system.

The second study presented at this year’s International AIDS Conference analyzed vaginal washings from 688 women in the original CAPRISA trial. Adam Burgener of the University of Manitoba and Nichole Klatt of the University of Washington realized that not only does the vaginal microbiome influence the likelihood of HIV infection, but also directly interferes with the efficacy of tenofovir, the ARV drug that was initially being tested. In fact, the tenofovir gel’s effectiveness was three times greater among women with high levels of vaginal Lactobacillus, but only conferred protection in 18% of women whose microbiomes were comprised of less than 50% Lactobacillus.

Burgener and Klatt found tenofovir to be far less effective when Lactobacilli were mixed with the bacterial strain Gardnerella vaginilis, which often takes over in the vaginal microbiota where Lactobacillus is scarce. That means that even if women in KwaZulu-Natal were able to access ARVs like PrEP, they would not be very effective in preventing the progression of this devastating disease because of the vaginal microbiota.

Phew, that was a lot of science. So what can we take away from all of this? It’s easy to interpret this research with a glass-half-empty perspective. Women throughout the world, whether they live in American cities or in rural, sub-Saharan Africa, are constantly being denied means of self-determination when it comes to their own reproductive health and wellbeing. This is the result of thousands of years of deeply ingrained cultural and social norms that permeate every culture and society. And as if entrenched inequality weren’t enough, now scientists are telling us that biology is screwing women over, too — that some women are scientifically destined to contract HIV more easily than men, often by no fault of their own.

I’m of the belief that these breakthrough studies should be cause for optimism for those who want to improve women’s health worldwide. As Chris Beyrer, president of the International AIDS Society, said, “These new insights pave the way to develop new prevention and treatment approaches that will protect the health of women, girls, and newborns . . . With women accounting for the majority of adults living with HIV in sub-Saharan Africa, and new infections among young women double that of young men in the region, it has never been more critical to address this vital issue.” Rather than reading these studies as cause for despair, we can instead view them as beacons of hope for HIV/AIDS research, treatment, and prevention that is especially geared toward the unique biological needs of women. Perhaps an intervention as simple as a probiotic taken to regulate acidic tummy troubles could, in fact, save thousands of young women’s lives and help bring about an AIDS-free generation.

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Lead image: flickr/jumblejet

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