Contraceptives, female reproductive tract inflammation and HIV risk

Contraceptives are used by millions of women worldwide and are critical to prevent unwanted pregnancies and reduce maternal and infant morbidity and mortality. However, previous studies have suggested that some hormonal and intrauterine methods may cause a shift in the microbiome towards a non-optimal state and increased inflammation in the female reproductive tract (FRT). Non-optimal microbiota and inflammation are, in turn, associated with higher risk of HIV acquisition (Masson et al., Clinical Infectious Diseases, 2015). These effects are however controversial, as several studies have yielded varying and sometimes contradictory findings. A possible explanation is that pre-existing demographic and biological differences influence the magnitude or direction of immune mediator and microbiome changes in response to contraceptives. We have shown that the effects of three commonly used contraceptives, depot medroxyprogesterone acetate, the copper intrauterine device and the levonorgestrel implant, were markedly influenced by the biological profiles of women before contraceptive initiation. Women who had low levels of FRT inflammation at baseline (i.e. are considered healthy) were most affected by contraceptives, experiencing much larger increases in inflammation than women with inflammation at baseline. Others have shown that injectable contraceptives increased HIV acquisition risk only in women with optimal, Lactobacillus-dominant microbiota, but not non-Lactobacillus communities. This study will utilise thousands of banked FRT and plasma samples from 356 women who acquired HIV and 1424 uninfected controls who participated in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomised clinical trial in Africa, where HIV risk is highest. Interactions between contraceptives, FRT inflammation and the microbiome will be investigated to determine their relative roles in HIV infection. This work will provide critical knowledge to inform contraceptive recommendations and choices, as well as novel contraceptive development.