Background:  Despite widespread use of oral and injectable hormonal contraception (HC), its effect on HIV risk remains unresolved. We evaluated the risk of HIV acquisition among women using oral contraceptive pills and injectable hormonal contraception in South Africa and Zimbabwe.

Methods:  We analyzed data from 4913 sexually active women aged 18 to 49 years participating in the Methods for Improving Reproductive Health in Africa (MIRA) study, a phase 3 effectiveness trial of the diaphragm and lubricant gel for HIV prevention. Participants attended quarterly visits for up to 24 months where they were interviewed about contraception and sexual behavior and were tested for pregnancy, HIV, and other sexually transmitted infections. We used Cox proportional hazards regression to estimate the risk of HIV acquisition among non-pregnant women who reported use of combined oral contraceptive pills (COC), progestin-only pills (POP), or injectable HC (depot medroxyprogesterone acetate [DMPA] and norethisterone enantate [Net-En]) compared to women not using these methods. Baseline contraceptive implant users were excluded and new users were censored at first implant use.

Results:  A total of 288 participants seroconverted during the study. Neither COC nor POP use was associated with an increased risk of HIV acquisition (see the table:  COC, adjusted hazard ratio 0.94, 95%CI 0.63 to 1.39; POP, HRa 0.84, 95%CI 0.45 to 1.56). In contrast, use of any injectable contraception was associated with an increased risk of HIV infection (HRa 1.41, 95%CI 1.04 to 1.91), but when disaggregated, neither DMPA nor Net-En significantly increased risk (HRa 1.38, 95%CI 0.96 to 1.98; HRa 1.32, 95%CI 0.73 to 2.39, respectively). A pre-specified analysis of modification by age and baseline HSV-2 status revealed that among HSV-2⁺ women at least 25 years of age, injectable use was associated with an increased risk of HIV infection compared with non-hormonal contraception (HRa 2.21, 95%CI 1.38 to 3.53).

Conclusions:  Oral and injectable contraceptives are highly effective and significantly reduce unintended pregnancies and maternal morbidity and mortality. However, these methods do not protect against HIV infection. The moderate increase in HIV risk among injectable users underscores the importance of dual protection with condoms and the need for diverse contraceptive options for women at risk of HIV infection.