Similar systemic but differential vaginal soluble mediator levels in injectable contraceptive users and impact of study site and STI prevalence

Abstract

The intramuscular (IM) injectable contraceptive, depo medroxyprogesterone acetate (DMPA-IM), the most common contraceptive in sub-Saharan Africa, may increase HIV susceptibility, unlike the injectable contraceptive norethisterone enanthate (NET-EN). Samples were taken at baseline and one week after the 24-week injection, from a subgroup of women randomized to DMPA-IM ( n = 49–50) or NET-EN ( n = 44–50), at two South African sites in the Women’s Health Injectable Contraceptive and HIV (WHICH) trial. We found that DMPA-IM and NET-EN similarly elevated select systemic soluble mediators. However, Durban participants showed decreases in vaginal adaptive immunity for DMPA-IM, but not NET-EN, consistent with greater HIV acquisition risk for DMPA-IM than NET-EN. Two growth factors were differentially regulated by the progestins in a vaginal epithelial cell line model, consistent with the clinical data at the Durban site. Most vaginal soluble mediators increased at the East London site for both contraceptives. Higher STI prevalence was observed at the East London site, which was associated with increased vaginal soluble mediator levels, which may mask the effects of contraceptives on the vaginal immune profile. Registry: PACTR https://pactr.samrc.ac.za/Search.aspx , TRN: 202009758229976, Registration date: 1 September 2020.