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). DESIGN: Open-label, nonrandomized, clinical trial. SETTING: University hospital clinic. PATIENT(S): Thirty HIV-infected women; 15 using ARV therapy (AZT, 3TC, and EFV) and 15 non-users of ARV therapy, followed biweekly for 12 weeks. INTERVENTION(S): Single injection of DMPA (150 mg IM) for both groups. MAIN OUTCOME MEASURE(S): Pharmacokinetic parameters of DMPA by liquid chromatography with mass spectrometry, and ovulation by serum P. RESULT(S): 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. CONCLUSION(S): 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.