Introduction Observational data suggest HIV-1 acquisition differs between users of two common injectable progestin-only contraceptives (IPC), depot medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN). Data are limited on the potential impact of both IPC types on herpes simplex virus type 2 (HSV-2) acquisition.

Methods We conducted a secondary analysis among IPC users enrolled at South African sites in VOICE, a multi-centre randomised trial of topical and oral HIV-1 chemoprophylaxis. Contraceptive use assessment was conducted monthly. HSV-2 was diagnosed by Focus HerpeSelect EIA at enrollment and repeat EIA at study exit in all participants (seroconversion cutoff value ≥3.5); quarterly EIA was available for a subset to assess seroconversion timing. Using Cox proportional hazards regression, we assessed the association between IPC type and HSV-2 acquisition with adjustment for potential confounders (age, marriage/cohabitation, education, condom use, number of partners, VOICE study arm).

Results Among 1776 IPC users who were HSV-2-seronegative at enrollment, 922 (51.9%) used DMPA, 716 (40.3%) used NET-EN, and 138 (7.8%) used both IPC types at different times during follow-up. Among the 1638 IPC users who did not switch IPC type during follow-up, 1506 (91.9%) had baseline and exit HSV-2 serology available. Over 1534.1 person-years (py) of follow-up, 178 incident HSV-2 cases occurred: 107 in DMPA users (crude incidence rate [IR] 11.3/100 py) and 71 in NET-EN users (crude IR 12.1/100 py). Among 640 participants with quarterly HSV-2 serology, 45 cases occurred among DMPA users over 350.4 py and 31 among NET-EN users over 231.1 py (HR = 0.97; 95% CI 0.61–1.53; aHR = 1.02; 95% CI 0.64–1.62).

Conclusion HSV-2 risk did not differ by DMPA versus NET-EN use. These results are consistent with our findings that DMPA users in VOICE did not have higher risk of genital tract infection (gonorrhoea, chlamydia or trichomoniasis) compared to NET-EN users, despite having higher risk for HIV-1 infection.

Disclosure of interest statement The authors report no conflicts of interest.