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.