Doubled etonogestrel dose linked to enhanced contraception in HIV-positive women on efavirenz

Placement of two etonogestrel implants instead of one appears to suppress ovulation and increase plasma etonogestrel exposure, thereby increasing contraceptive effectiveness in HIV-positive women on efavirenz-based antiretroviral therapy (ART).

The study included 72 cisgender Ugandan women (median age 31 years) with regular menstrual periods who were receiving efavirenz-based ART for HIV. These women were randomly assigned to receive two etonogestrel implants (136 mg; n=36, double implant group) or one etonogestrel implant (68 mg; n=36, control group). The implants were placed in the same arm. All participants also used a copper intrauterine device to prevent pregnancy

Researchers compared the rate of ovulation and etonogestrel pharmacokinetics between the two groups. Ovulation was evaluated by measuring weekly serum progesterone concentrations over 4 consecutive weeks at months 3 (weeks 9–12), 6 (weeks 21–24), and 12 (weeks 45–48), with concentrations of >3 ng/mL being interpreted as ovulation. Meanwhile, etonogestrel concentrations were measured from plasma samples collected at day 3 and weeks 1, 4, 12, 24, 36, and 48 after implant placement.

There were two participants in the control group who withdrew from the study, one at week 1 because of undetected pregnancy at entry and another at week 45 because of clinically significant depression. Ovulations occurred with significantly less frequency in the double implant group than in the control group (month 3: 0 percent vs 31 percent; month 6: 0 percent vs 49 percent; month 12: 6 percent vs 56 percent; p<0.001 for all). The placement of two etonogestrel implants reduced the odds of ovulation by 97.7 percent over 48 weeks.

Moreover, etonogestrel concentration was more than twofold higher in the double implant group than in the control group at each time point, with a geometric mean ratio of 2.83 at week 48.

In terms of safety, the incidence of adverse events was comparable between the two groups, and none of the participants discontinued because of adverse events.