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Introduction: HIV eradication is not feasible and lifelong treatment is warranted to manage HIV infection. In this scenario, the advent of single-tablet, once-daily, fixed-dose co-formulations is important for reducing pill burden and maximize long-term drug adherence. Cobicistat-boosted darunavir along with emtricitabine and tenofovir alafenamide co-formulation (DRV/c/FTC/TAF or the trade name Symtuza®) is the first marketed protease inhibitor-based fixed-dose combination regimen for the treatment of HIV infection. It was approved in late 2017 by the European Medical Agency both for naïve patients and treatment-experienced patients with viral suppression. Areas covered: PubMed, ClinicalTrials.gov and presentations at scientific meetings were searched with the terms 'darunavir/cobicistat' and 'tenofovir alafenamide and emtricitabine' for clinical trials either conducted to date or ongoing as well as a review of abstracts from major HIV/AIDS and infectious diseases conferences from 2015 to up to date. Expert opinion: DRV/c/FTC/TAF is a novel unique antiretroviral drug co-formulation that exhibits a convenient dosing, satisfactory safety profile, and high antiviral efficacy, even in patients harboring viruses with resistance to antivirals other than darunavir in the short-midterm. It represents the first fixed-dose combination therapy including a protease inhibitor given as one single pill once daily for drug-naïve patients and as second-line antiretroviral therapy.