ACTG Study A5338 Raises Potential Concern about Standard DMPA Dosing Frequency among African Women Receiving HIV and TB Treatment

The Lancet HIV, September 2019

Tuberculosis (TB) coinfection among pregnant women living with HIV is associated with poor outcomes so effective contraception to prevent unintended pregnancy is of paramount importance for young women with HIV and TB. However, hormonal contraceptives can fail as result of drug-drug interactions (DDI) between these agents and TB or antiretroviral treatments (ART). The A5338 study was designed to identify the ideal dosing frequency for DMPA among women with HIV-TB coinfection and determine whether a 150 mg injection of DMPA was effective in preventing ovulation.

Participants were on RIF-based TB treatment and EFV-based ART and given DMPA at study entry, with levels of the active metabolite of DMPA measured every 2 weeks. Their results were compared with those from women taking DMPA, but neither ART nor TB treatment, from the control arm of a separate study (A5093). The results of A5338 demonstrate that EFV-based ART in combination with RIF-based TB treatment reduced the amount of DMPA to a level associated with a risk of ovulation in 12 percent of women. Researchers also found that DMPA was cleared faster among women with HIV on ART AND RIF-based TB treatment, suggesting that more frequent dosing might be necessary.

Pharmacokinetics and Pharmacodynamics of Depot Medroxyprogesterone Acetate (DMPA) in African women receiving treatment for HIV and TB: Potential concern for standard dosing frequency.