Pre-exposure Prophylaxis for HIV-1 Prevention Does Not Diminish the Pregnancy Prevention Effectiveness of Hormonal Contraception

Pamela M. Murnane; Renee Heffron; Allan Ronald; Elizabeth A. Bukusi; Deborah Donnell; Nelly R. Mugob; Edwin Were; Andrew Mujugira; James Kiarie; Connie Celum; Jared M. Baeten


AIDS. 2014;28(12):1825-1830. 

In This Article

Abstract and Introduction


Background: For women at risk of HIV-1, effective contraception and effective HIV-1 prevention are global priorities.

Methodology: In a clinical trial of pre-exposure prophylaxis (PrEP) for HIV-1 prevention in HIV-1-serodiscordant couples, we estimated the effectiveness of hormonal contraceptives (oral contraceptive pills, injectable depot medroxyprogesterone acetate, and hormonal implants) for pregnancy prevention relative to no contraception among 1785 HIV-1-uninfected women followed up to 36 months. We compared the effectiveness of each method among women assigned PrEP versus placebo. Contraception was not required for participation, but was offered on-site and was recorded monthly; incident pregnancy was determined by monthly urine testing.

Results: For women using no contraception, overall pregnancy incidence was 15.4% per year. Women reporting oral contraceptive use had comparable pregnancy incidence to women using no contraception, and this lack of contraceptive effectiveness was similar for those assigned PrEP and placebo (17.7 and 10.0% incidence per year, respectively; P-value for difference in effect by PrEP use = 0.24). Women reporting injectable contraception had reduced pregnancy incidence compared to those reporting no contraception, which did not differ by arm (PrEP 5.1%, placebo 5.3% per year; P-value for difference = 0.47). Contraceptive effectiveness was highest among women using implants (pregnancy incidence <1% per year in both arms).

Conclusion: PrEP had no adverse impact on hormonal contraceptive effectiveness for pregnancy prevention. As seen previously in similar populations, women reporting contraceptive pill use had little protection from pregnancy, possibly due to poor adherence. Injectable or implantable hormonal contraception and PrEP provide effective prevention for pregnancy and HIV-1.


Women account for nearly one-half of new HIV-1 infections worldwide and the majority of new infections in Africa. For women at risk of HIV-1, effective contraception and effective methods of HIV-1 prevention are public health imperatives. Hormonal forms of contraception are highly effective for the prevention of unintended pregnancy, although some observational studies suggest hormonal contraceptive use may increase susceptibility to HIV-1,[1,2] further necessitating effective HIV-1 prevention strategies for women. Antiretroviral pre-exposure prophylaxis (PrEP) is a promising new HIV-1-prevention strategy, and joint use of hormonal contraception and PrEP could offer dual protection. However, in a recent clinical trial of PrEP conducted among women in sub-Saharan Africa, more pregnancies were observed among women randomized to daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) PrEP compared to placebo,[3] raising a concern that PrEP potentially reduces the pregnancy-prevention effectiveness of hormonal contraception.[4] The few published pharmacokinetic studies of TDF and hormonal contraception have shown mixed results, with one study finding no evidence of reduced plasma oral contraceptive concentrations when the products were used together,[5] whereas another found use of oral and injectable hormonal contraceptives reduced cellular levels of TDF metabolites.[6] Data directly measuring pregnancy incidence among women using both PrEP medications and hormonal contraceptives are very limited,[7] and further evidence is needed to ensure there are no adverse interactions between PrEP and hormonal contraceptives. We assessed the impact of TDF-based PrEP on hormonal contraceptive effectiveness in a large clinical trial of PrEP for HIV-1 prevention.