Contraceptives
Hormones used in hormonal contraception can also interact with antiretrovirals due to overlapping metabolism via CYP450 enzymes, and/or glucuronidation . Women of child-bearing potential make up a significant portion of the population living with, or at risk of, HIV, and therefore DDIs between ART and hormonal contraceptives are of significant relevance. In HPTN 077, a phase 2a trial of the safety, tolerability, and pharmacokinetics of two doses of long-acting cabotegravir, 79 of the 85 cisgender women in the trial were on hormonal contraception . In a secondary analysis, oral contraception was associated with a 25% lower peak concentration of cabotegravir, compared to women not on hormonal contraception. Importantly, trough concentration (and other pharmacokinetic parameters AUC, t½, and time to unquantifiable concentrations) were not affected and this small difference in peak concentrations is unlikely to be clinically significant. Notably, this analysis did not look at hormone concentrations but significant changes in hormone exposures are not anticipated given that neither cabotegravir nor rilpivirine act as metabolic inducers. These results were corroborated by a similar sub-study in HPTN 084 noting a lack of clinically relevant interaction.
Other data assessing LAI ART and hormonal contraception is limited. Of the other common hormonal contraceptive methods, including depot medroxyprogesterone acetate (DMPA) or progestin-based implants, no significant DDIs are expected. Extrapolating from oral rilpivirine and cabotegravir, modest interactions may be expected but unlikely to result in clinically significant changes. Daily oral rilpivirine has been studied with ethinylestradiol and norethindrone oral contraceptive, for example, and was found to increase peak ethinylestradiol by only 17% with no effect on norethindrone concentrations . In another study, daily oral cabotegravir increased levonorgestrel peak concentrations by about 12% with no effect on ethinylestradiol . No effects were found on cabotegravir pharmacokinetics, nor on contraception pharmacodynamic endpoints such as luteinizing hormone, follicle-stimulating hormone, or progesterone concentrations.
In summary, all hormonal oral and long-acting contraception can be used without concern in people receiving LAI cabotegravir and/or rilpivirine.