Effective contraception is critical to young women with HIV-associated tuberculosis (TB), as unintended pregnancy is associated with increased maternal illness and death. The effects of co-administration of efavirenz and rifampicin on the mechanisms of action of depot medroxyprogesterone acetate (DMPA) are unknown. We hypothesized that clearance of medroxyprogesterone acetate (MPA) would increase when given with rifampicin and efavirenz, thus increasing risk of pregnancies. This pharmacokinetics (PK) study assessed DMPA among HIV/TB coinfected women on an efavirenz-based antiretroviral treatment and rifampicin-based TB treatment. Plasma MPA concentrations and progesterone were measured before dosing (MPA only) and 2, 4, 6, 8, 10, and 12 weeks after a single DMPA 150 mg intramuscular injection. The primary outcome measure, MPA concentration (less than 0.1 ng/mL) at week 12, was assessed and the parameters of MPA mechanism of action were calculated using statistical analysis. Among 42 evaluable women from 5 African countries, median age was 32 years and median CD4 was 414 cells/ mm3. Five women had MPA less than 0.1 ng/mL at week 12; of these, one had MPA less than 0.1 ng/mL at week 10. The median clearance of MPA was 19 681 L/week compared with 12 118 L/week for historical controls. There were no adverse events related to DMPA, and progesterone concentrations were less than 1 ng/mL for all women for the study duration. In conclusions, DMPA when given with rifampicin and efavirenz, was safe. MPA clearance was higher than in women with HIV and not on any Anti-HIV treatment suggesting that more frequent DMPA dosing might be needed.

This is a phase II open-label, single arm, multicenter, steady-state pharmacokinetic (PK) study of drug-drug interactions in Human Immunodeficiency Virus (HIV) infected women treated with depot medroxyprogesterone acetate (DMPA) while receiving an efavirenz (EFV)-based combination antiretroviral therapy (cART), rifampicin (RIF) and isoniazid (INH) during the treatment of active tuberculosis (TB). The objectives of this study are to estimate the optimal dosing frequency of depot medroxyprogesterone acetate (DMPA) for HIV and TB coinfected women taking EFV-based cART and RIF-containing TB treatment based on a target MPA concentration >0.1 ng/mL and to determine whether a 150 mg DMPA IM injection will be adequate to suppress ovulation through 12 weeks in women taking EFV-based cART and RIF-containing TB treatment based on serial plasma progesterone concentrations. Premenopausal women 18 to 46 years of age who are co-infected with HIV and TB and are on EFV plus two or more nucleoside reverse transcriptase inhibitors (NRTIs) for at least 4 weeks and intend to continue on this regimen without modifications for the duration of the study will participate. The women must also be on the continuation phase of active TB treatment taking RIF and INH on a 5-day or more per week schedule. Blood samples for DMPA PK analysis will be collected at pre-dose and every 2 weeks post DMPA administration. Progesterone levels will be tested every 2 weeks post DMPA administration. Depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly (IM) as a single-dose at study entry and an optional dose of DMPA will be available at no cost to all qualifying study participants after all week 12 study evaluations are completed. The sample size will comprise 46 evaluable participants who will be followed for 12 weeks The results of this study, if successful, will help inform the optimal frequency of DMPA injections in HIV/TB co-infected patients.