Women are more susceptible to HIV-1 than men, with approximately 40% of all HIV-1 infections originating in the female genital tract (FGT). Increasing evidence suggests that sex hormones – such as those found in hormonal contraceptives – affect HIV-1 susceptibility through direct and indirect mechanisms involving inflammation and immune responses. In a recent review in Disease Models & Mechanisms, Postdoctoral Fellow Dr. Jocelyn Wessels of Dr. Charu Kaushic’s lab takes an extensive look at the current literature to propose viable correlations between the sex-hormone–microbiome–immunity axis and HIV-1 susceptibility in women.
Wessels’ proposes in her study that the observed impact of sex hormones on HIV-1 susceptibility could be directly connected with their ability to regulate the composition of microbes within the vaginal tract. Estradiol, for example, has been shown to play a significant role in establishing a microenvironment within the vaginal microbiota that is largely lactobacillus-dominated. In contrast, DMPA – a progestin-based injectable contraceptive recently found to vastly increase HIV-1 susceptibility in women – depletes estradiol in the female genital tract, leading to a reduced population of lactobacilli and a more diverse array of other bacteria within the vaginal microbiota. Interestingly, studies have shown that a vaginal microbiota dominated by lactobacillus species has a protective effect against HIV-1, as lactobacilli appear to reduce innate inflammation and, subsequently, the potential number of HIV target cells. On the other hand, complex bacterial compositions – such as those seen in women using DMPA – have been found to correlate with increased HIV-1 susceptibility, as diverse compositions may induce innate immunity, upregulating cytokines, inflammation and activated T cells – a major target of HIV-1.
Although additional research is critically needed in this area, Dr. Wessels’ extensive review on the determinants of HIV-1 susceptibility allows us to draw a number of reasonable correlations regarding sex hormones, the human microbiome, and the immune system. Such insights will consequently help inform further clinical studies in this area, which could lead to new or improved HIV-1 treatments and prevention strategies.
Read the full review in Disease Models & Mechanisms here.