OBJECTIVE To evaluate the effect of an antiretroviral (ARV) therapy regimen containing zidovudine (AZT), lamivudine (3TC), and efavirenz (EFV) on the pharmacokinetics of depot medroxyprogesterone acetate (DMPA). METHODS Open-label, nonrandomized, clinical trial. METHODS University hospital clinic. METHODS Thirty HIV-infected women; 15 using ARV therapy (AZT, 3TC, and EFV) and 15 non-users of ARV therapy, followed biweekly for 12 weeks. METHODS Single injection of DMPA (150 mg IM) for both groups. METHODS Pharmacokinetic parameters of DMPA by liquid chromatography with mass spectrometry, and ovulation by serum P. RESULTS Maximum serum concentrations of DMPA were reached at 14 days after injection. The area under the curve was similar in both groups, as were the minimum concentration, half-life, and clearance. Only 1 woman, not using ARV therapy, ovulated at 11 weeks after DMPA. CONCLUSIONS Pharmacokinetics of DMPA were similar in HIV-infected women, regardless of ARV therapy use, suggesting that triple therapy with AZT, 3TC, and EFV is not likely to interfere with the contraceptive effectiveness of DMPA.