Exploring drug interactions of protease inhibitors to treat HIV

Protease inhibitors (PIs) remain critical for managing HIV, particularly in cases of drug resistance or as alternatives to first-line therapies. Currently, integrase strand transfer inhibitors (InSTIs), such as dolutegravir and bictegravir, are preferred third agents in first-line regimens due to their efficacy and lower risk for drug-drug interactions. However, boosted PI regimens, which include drugs such as darunavir combined with ritonavir or cobicistat, serve as key alternatives when resistance or intolerance to InSTIs arises. Boosting agents inhibit the CYP3A4 enzyme, significantly enhancing PI plasma levels and therapeutic efficacy. Despite this benefit, the boosting mechanism introduces a major clinical challenge: drug interactions with medications metabolized by CYP3A4. These interactions can influence therapeutic outcomes, either by increasing side effects or reducing the efficacy of co-administered drugs.

The need for careful management of drug interactions in boosted PI regimens becomes even more critical when considering adherence — 1 of the most significant barriers to the success of ART. Complex dosing schedules and high pill burdens often undermine treatment consistency, jeopardizing viral suppression and increasing the risk for resistance. STRs address these challenges by consolidating multiple medications into a single daily pill, simplifying therapy and improving patient persistence. By reducing the pill burden and ensuring all components are taken simultaneously, STRs enhance adherence and treatment outcomes compared with MTRs, providing a convenient option for darunavir-based therapy. While fixed-dose STRs offer a convenient and effective option for darunavir-based therapy, clinicians must remain vigilant for potential drug interactions associated with boosted regimens.

Ken S. Ho, MD, MPH, is an infectious disease specialist based in Pittsburgh, Pennsylvania, with affiliations at University of Pittsburgh Medical Center (UPMC) Presbyterian Shadyside and UPMC Magee-Womens Hospital. He serves as an associate professor of medicine in the Division of Infectious Diseases at the University of Pittsburgh School of Medicine and as the medical director of the Pitt Men’s Study, a key component of the Multicenter AIDS Cohort Study. His clinical expertise focuses on HIV care and pre-exposure prophylaxis, and his research centers on advancing HIV prevention strategies. In an article, published in Infectious Disease Advisor, Dr Ho discusses drug interactions of PIs to consider when treating HIV.

Read the full article here.