Efavirenz and rifampicin together reduce levels of injectable contraception

Women with HIV receiving depot medroxyprogesterone acetate (DMPA), with efavirenz (EFV)-based ART and rifampicin (RIF)-based TB treatment, had lower MPA plasma levels compared with women not receiving the two drugs.

These findings from ACTG A5338 were presented by Rosie Mnqibisa from the Enhancing Care Initiative, Durban, South Africa, on behalf of the study group.

Effective contraception is vital for young women with HIV-associated TB. Unintended pregnancy in this population is linked to increased maternal and infant disease and death.

RIF and EFV both induce CYP3A4 leading to lower progestin exposure and, in turn, reduced hormonal contraceptive effectiveness. DMPA is a contraceptive method that is given as an intramuscular injection and commonly used in low- and middle-income countries. The effect on the pharmacokinetics (PK) and safety of using DMPA with both EFV and RIF has not been previously investigated.

ACTG A5338 was a multicentre, single arm, PK study among women in sub Saharan Africa, stable on EFV-based ART and RIF-based TB treatment. It was conducted to estimate optimal dosing frequency of DMPA for women with HIV and TB receiving EFV and RIF and to look at whether standard 150 mg DMPA would be adequate to suppress ovulation through 12 weeks in this population.

Target serum MPA concentration was >0.1 ng/mL. Concentrations were determined pre-dose and 2, 4, 6, 8, 10 and 12 weeks after DMPA injection and progesterone levels measured from week 2 onwards. The primary outcome was the proportion of women with subtherapeutic MPA levels at week 12. MPA PK parameters were compared to historical controls.

A total of 42 women from Botswana, Zimbabwe, Kenya and South Africa were included in this PK analysis. All women were black African; at baseline they were a median of 32 years old and 54 kg; 86% had viral load <400 copies/mL.

All women had MPA levels above <0.1 ng/mL at week 8. At week 10, 1 woman had levels that fell below this target. By week 12, 5 (11.9%) women had MPA levels <0.1 ng/mL (95% CI 4.2 to 26.8).

Apparent clearance was higher in study population vs controls: 19,680 vs 12,117 respectively, p=0.004. Median AUC over 12 weeks was lower: 7.63 vs 12.38 ng*week/mL respectively, p=0.004.

Progesterone levels were below 1ng/mL through week 12 for all women; no ovulation occurred.

There were no grade 3 or higher adverse effects attributed to DMPA. There were no reported pregnancies.

The investigators suggested that shortening the DMPA dosing interval for women receiving EFV and RIF, most likely to every 8–10 weeks, seems prudent.