Abstract
Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. However, hormonal contraceptive (HC) use may influence HIV risk through changes in genital tract microbiota and inflammatory cytokines. To investigate this, 130 HIV negative adolescent females aged 15–19 years were enrolled into a substudy of UChoose, an open-label randomized crossover study (NCT02404038), comparing acceptability and contraceptive product preference as a proxy for HIV prevention delivery methods. Participants were randomized to injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) or etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR) for 16 weeks, then crossed over to another HC for 16 weeks. Cervicovaginal samples were collected at baseline, crossover and exit for characterization of the microbiota and measurement of cytokine levels; primary endpoints were cervical T cell activation, vaginal microbial diversity and cytokine concentrations. Adolescents randomized to COCs had lower vaginal microbial diversity and relative abundance of HIV risk-associated taxa compared to Net-En or CCVR. Cervicovaginal inflammatory cytokine concentrations were significantly higher in adolescents randomized to CCVR compared to COC and Net-En. This suggests that COC use may induce an optimal vaginal ecosystem by decreasing bacterial diversity and inflammatory taxa, while CCVR use is associated with genital inflammation.
Highlights
Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies
We found that adolescents assigned to COC had more lactobacilli compared to those assigned to norethisterone enanthate (Net-En), and those assigned to contraceptive vaginal ring (CCVR)
This study focused on adolescent females, who are at the highest risk for both unintended pregnancies and HIV acquisition
Summary
Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. Adolescents randomized to COCs had lower vaginal microbial diversity and relative abundance of HIV risk-associated taxa compared to Net-En or CCVR. We hypothesized that the long-acting injectable progestin Net-En may alter vaginal microbiota, causing increased genital inflammation, but that COC and CCVR, due to their estrogen component, would not. We assessed temporal changes in cervicovaginal microbiota and cytokines in adolescents randomized to three HCs: the long-acting progestinonly injectable Net-En, combined oral contraceptives (COC) Triphasil® or Nordette® and NuvaRing®, a CCVR containing etonorgesterol/ethinyl estradiol. CCVR use was associated with significantly elevated genital tract inflammation compared with both Net-En and COC Together, these data suggest that COC may benefit women at high risk for BV and HIV
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