Research in context
Evidence before this study
We searched PubMed for articles published before July 7, 2015, using the search terms “depo provera” OR “dmpa” OR “nur isterate” OR “net-en” AND “HIV” and read those written in English. We examined relevant citations from the results of our search and identified studies that examined HIV acquisition and contraceptive use from an epidemiological perspective, with some, but not all, reporting a significant association. We also identified studies that assessed the effect of progestins on the function of immune cells in vitro, in animal models, in ex-vivo tissue, or in blood or assessed cohorts not at high risk of HIV acquisition. Some studies examined the biological associations with contraceptive use in high-risk cohorts but limited their observations to soluble immune mediators and did not find a concomitant increase in HIV acquisition risk.
Added value of this study
Previous studies examining the epidemiological risk of injectable progestin-only contraceptive use and HIV acquisition have variably been confounded by differences in behavioural risk factors reported between those using no long-term contraceptive and injectable progestin-only contraceptive users. These confounders might have masked potential biological effects of injectable progestin-only contraceptive use. Our study characterises a unique cohort of young women in which profiles of HIV risk factors had similar proportions across the cohort, so women using injectable progestin-only contraceptives and women using no hormonal contraception were similar in terms of HIV risk factors.
In this study, we identified an increased frequency of HIV target cells at the cervix of HIV-negative women using injectable progestin-only contraceptives and, in the same group of women, noted a significantly higher incidence of HIV acquisition in injectable progestin-only contraceptive users. We noted a similar pattern in HIV target cell frequency in the naturally high progestin state of the luteal phase in women not using long-term contraceptive, suggesting that progestins, both endogenous and exogenous, might be key mediators of target cell availability. Our work links epidemiological observations of HIV infection to the immunological effects of injectable progestin-only contraceptive use in the female genital tract and provides new mechanistic insight into the role of progestins in HIV acquisition risk in women.
Implications of all the available evidence
Our results, taken together with other studies, have cast further doubt about the safety of injectable progestin-only contraceptive in areas of high HIV incidence. Moreover, by concluding that a high progestin concentration, both in naturally cycling women and in injectable progestin-only contraceptive users, correlates with increased target cell availability at the cervix, we suggest that progestins might induce increased cervical HIV target cell frequency. This work provides new insight into the role of progestins in the female genital tract and might inform the development of biological prophylactics to reduce HIV acquisition for women.