Prevention of HIV-1 and unplanned pregnancy are global public health priorities for reproductive-aged women. HIV-1 treatment with non-nucleoside reverse transcriptase inhibitors (NNRTIs) has been associated with a reduced effectiveness of some hormonal contraceptives for pregnancy prevention, particularly implantable methods. A vaginal ring containing dapivirine, a novel NNRTI, has demonstrated effectiveness for HIV-1 prevention; the potential for a drug-drug interaction between vaginally-delivered dapivirine and contraceptive effectiveness has not been assessed in epidemiologic studies.
MTN-020/ASPIRE was a randomized, double-blind, placebo-controlled phase III safety and effectiveness study of the dapivirine vaginal ring for HIV-1 prevention. Sexually active women aged 18-45 years from Malawi, South Africa, Uganda, and Zimbabwe were enrolled. Use of a highly effective method of contraception was a criterion for study participation. At monthly visits, current contraceptive method was recorded on a standardized form and urine pregnancy tests were performed. If a participant became pregnant, study product was withheld for the duration of pregnancy and breastfeeding. Pregnancy incidence by arm was calculated separately for each contraceptive method and compared using an Andersen-Gill proportional hazards model stratified by site and censored at HIV-1 infection.
Of 2629 women enrolled, 2536 women returned for follow-up and reported using a highly effective contraceptive method during study participation (1263 in the dapivirine arm, 1273 in the placebo arm). Overall pregnancy incidence among women reporting use of injectable depot medroxyprogesterone acetate (DMPA), injectable norethisterone enanthate (NET-EN), hormonal implants, or oral contraceptive pills (OCPs) was: 0.49, 0.58, 0.45, and 30.21 per 100 person-years, respectively. Pregnancy incidence did not differ for those assigned active dapivirine vaginal ring versus placebo ring for any of the hormonal contraceptive methods (Table).
Dapivirine vaginal ring use was not associated with diminished hormonal contraceptive effectiveness for pregnancy prevention. Oral contraceptive pill use was associated with high pregnancy incidence, which may be due to poor pill adherence. Injectable and implantable methods were highly effective in preventing pregnancy.