The Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial found no substantial difference in HIV acquisition risk between women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or the levonorgestrel (LNG) implant. However, ECHO did not address whether these contraceptives increase HIV risk relative to other contraceptive methods or to no contraception. We investigated the impact of DMPA-IM, copper IUD and LNG implant on cervicovaginal inflammatory profiles previously associated with HIV acquisition, among a sub-cohort of ECHO participants.
This study included 168 ECHO participants at the Setshaba Research Centre in Tshwane and MRU in eThekwini, South Africa. Eleven cytokines and antimicrobial peptides were measured in duplicate using Luminex in lateral vaginal wall swabs. Changes in cytokine concentrations were assessed using Wilcoxon signed rank test and generalized linear modelling. P values were adjusted for multiple comparisons using a false discovery rate procedure.
Baseline cervicovaginal cytokine concentrations were elevated in women with Neisseria gonorrhoeae infection and dampened among herpes simplex virus (HSV)-2 seropositive women. Younger women had higher concentrations of IL-8 and IL-1β. The copper IUD and LNG implant were associated with rapid increases in inflammatory markers following contraceptive initiation. Pro-inflammatory IL-1β and IL-6 and chemotactic IL-8, IP-10, MIP-1⍺ and MIP-1β were significantly elevated one month following copper IUD insertion. No changes were evident at one month post LNG implant insertion, however at three months, TNF-⍺, IP-10, MIP-3⍺ and SLPI were significantly raised relative to baseline. Significant effect modification was observed by N. gonorrhoeae and HSV-2 infection.
The copper IUD and the LNG implant are associated with increased cervicovaginal inflammatory markers that have been linked to HIV infection risk. These effects are modified by STI status. Recent studies have demonstrated the important interplay between inflammation, the microbiome, contraception and HIV risk. Continued research to understand these effects are critical for safe contraceptive use and to inform novel contraceptive development.