Response to: Pharmacokinetic and Pharmacodynamic Drug Interactions between Antiretrovirals and Oral Contraceptives

It is limiting and potentially damaging to consider that women should not be prescribed combined oral contraceptives or progestin-only pills when concurrently taking certain antiretrovirals, based on our limited understanding of drug-to-drug interactions. Instead, a woman should be empowered and educated to access the combination of healthcare behaviors and medications that optimize her well-being and safety. Additionally, scientists, drug developers, and clinicians should strive to collaborate to responsibly synthesize our scientific data into a sound physiologic framework. The progestin component of hormonal contraceptives thickens cervical mucus and prevents sperm from entering the upper genital tract. Hostile cervical mucus is the primary mechanism by which hormonal contraceptives prevent pregnancy [1]. It is reasonable to infer that an elevated or maintained progestogen level with the co-administration of protease inhibitors would result in thickened and impenetrable cervical mucus with maintained contraception. Combined hormonal contraception typically contains ethinylestradiol (EE) in addition to a progestogen. The added EE is considered to have additional mechanisms of action, such as ovulation suppression, and offers a more favorable side effect profile, with less irregular bleeding [2]. Drug interactions that result in decreased EE serum concentrations should not have an impact on cervical mucus if the progestogen exposure is maintained. Furthermore, women are currently prescribed products with 10 lg EE doses, such as Lo Loestrin Fe, and are not specifically counseled on reduced contraceptive efficacy due to lower potential EE exposure. Contraceptive efficacy as defined by the Pearl Index in FDA trials, or typical use as defined by epidemiologic population-based data, are not determined by secondary markers and pharmacokinetic outcomes, such as those defined in the review by Tittle et al. [3] Clinicians and researchers should consider engaging in a discussion that explores the potential disparities between statistical and clinical significance, with the goal of executing research that focused on clinically significant measures. A mean area under the concentration-time curve difference of 10, 20, or 40 % may not be a clinically significant change, especially if that component was developed to minimize breakthrough bleeding or side effect profiles. If one of my patients requests combined oral contraceptives but is taking an interacting medication, I offer guidance and alternatives, and counsel on the benefits of long-acting reversible contraception, in addition to the use of condoms. If she does not have a contraindication, I prescribe her method of choice, with close follow-up and repeat counseling. I applaud Tittle et al. [3] for their eloquent and replete compilation of our peer-reviewed research regarding antiretrovirals and oral contraceptives. However, I caution that we lack robust epidemiologic data to conclude, in several instances, that efficacy is reduced. We must strive for better research and equitable interpretation of the data to engender access and enhanced reproductive justice for our HIV-positive women.