Drug-drug interactions between antiretrovirals and hormonal contraception: An updated systematic review.

Objective: To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs).

Study design: Systematic review.

Results: We included 49 articles, with clinical, ARV, or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations.

Conclusion: TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counseling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice.

Implications: Most ARVs and HCs may be used safely and effectively together. Efavirenz-based ART requires careful counseling and data for possible interactions between HCs and new ARV classes are anticipated.