The advent of protease inhibitors (PI) in the mid-nineties and its use as part of triple combinations revolutionized the management of HIV infection. Since then, progression to AIDS and AIDS-related deaths can be prevented. However, antiretroviral therapy based on PI has been discouraged for a while given its lower tolerability compared to alternative options; and only recent improvements in pharmacotherapy have renewed the interest for the newest agents within this class. First, the tolerability of the latest PI darunavir (DRV) and atazanavir is much better than for older PI, such as indinavir or lopinavir. Second, metabolic abnormalities and/or drug interactions associated to ritonavir boosting have been ameliorated using cobicistat. Third, adding safer accompanying nucleos(t)ides, such as tenofovir alafenamide (TAF), have minimized further toxicity concerns of PI. Finally, the unique barrier to resistance and new single-tablet regimen (STR) presentation makes DRV, especially attractive for long-term therapy. The recent coformulation of DRV, cobicistat, TAF, and emtricitabine (DRV/c/TAF/FTC) within a single pill to be given once daily (Symtuza®) has positioned PI again at the frontline of HIV therapeutics. In this review, we discuss the results of studies that have assessed the efficacy and safety of the newest STR. In view of the current data, it seems worthy expanding the consideration of Symtuza® for a wider range of clinical scenarios, beyond the treatment of antiretroviral failures including first-line therapy and switching of otherwise virologically suppressed patients. The good tolerability and robust resistance profile should reward Symtuza® and position it among the preferred contemporary STRs.
Keywords: Bictegravir; Darunavir; Dolutegravir; Single-tablet regimens; Tenofovir alafenamide; Tolerability.
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