HIV disease progression by hormonal contraceptive method

HIV disease progression by hormonal contraceptive method: secondary analysis of a randomized trial.

HIV-infected women need access to safe contraception. Stringer and colleagues hypothesized that women using depomedroxyprogesterone acetate (DMPA) contraception would have faster HIV disease progression than women using oral contraceptive pills and nonhormonal methods. In a previously reported trial, the authors randomized 599 HIV-infected women to the intrauterine device (IUD) or hormonal contraception. Women randomized to hormonal contraception chose between oral contraceptive pills and DMPA. This analysis investigates the relationship between exposure to hormonal contraception and HIV disease progression [ defined as death, becoming eligible for antiretroviral therapy, or both]. Of the 595 women not on antiretroviral therapy at the time of randomization, 302 were allocated to hormonal contraception, of whom 190 (63%) initiated DMPA and 112 (37%) initiated oral contraceptive pills. Women starting IUD, oral contraceptive pills, or DMPA were similar at baseline. Compared with women using the IUD, the adjusted hazard of death was not significantly increased among women using oral contraceptive pills [1.24; 95% confidence interval (CI) 0.42-3.63] or DMPA (1.83; 95% CI 0.82-4.08). However, women using oral contraceptive pills (adjusted hazard ratio (AHR) 1.69; 95% CI 1.09-2.64) or DMPA (AHR 1.56; 95% CI 1.08-2.26) trended toward an increased likelihood of becoming eligible for antiretroviral therapy. Women exposed to oral contraceptive pills (AHR 1.67; 95% CI 1.10-2.51) and DMPA (AHR 1.62; 95% CI 1.16-2.28) also had an increased hazard of meeting this study’s composite disease progression outcome (death or becoming antiretroviral therapy eligible) than women using the IUD. In this secondary analysis, exposure to oral contraceptive pills or DMPA was associated with HIV disease progression among women not yet on antiretroviral therapy. This finding, if confirmed elsewhere, would have global implications and requires urgent further investigation.

The relationship between hormonal contraception and disease progression was not an a priori hypothesis of this trial and 47% of the participants switched contraceptive methods, withdrew from the study, or were lost to follow-up. The researchers addressed the switching by treating contraceptive method as a time-varying exposure but the fact that women assigned to the contraceptive arm could choose either DMPA or oral contraceptives could have introduced confounding. Given that the risk of maternal mortality increases with each subsequent pregnancy, with a women’s lifetime risk of dying in pregnancy as high as one in 22 in sub-Saharan Africa, women need safe and effective contraception when they want it. These results are by no mean definitive but they support the urgent call for a trial evaluating the potential relationship between HIV disease progression and hormonal contraception.