A four-drug combination oral tablet of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide for the treatment of HIV-1 infection in adults

ABSTRACT

Introduction

Darunavir (DRV)/cobicistat (COBI)/emtricitabine (FTC)/tenofovir alafenamide (TAF) is the only protease inhibitor-based single-tablet regimen (STR) approved for the treatment of HIV infection of adults and pediatric patients weighing at least 40 kg. DRV/COBI/FTC/TAF has demonstrated to be an effective regimen, to have a high genetic barrier to resistance, and to be well tolerated.

Areas covered

The authors summarize the chemistry and pharmacology of DRV, COBI, FTC, and TAF and discuss trials conducted on antiretroviral therapy (ART)-naïve and -experienced people living with HIV designed to evaluate safety, tolerability, and efficacy of the STR. This work also reports studies comparing DRV/COBI/FTC/TAF with competitive agents in real-world settings.

Expert opinion

Despite the availability of newer antiretroviral drugs and strategies in the management of HIV infection, including long-acting therapies, DRV/COBI/FTC/TAF is still considered an alternative regimen for the treatment of ART-naïve adults. DRV/COBI/FTC/TAF is an effective, well-tolerated, and safe antiretroviral regimen and represents a valid option for people who need to switch therapy due to tolerability issues, such as the onset of neuropsychiatric effects related to integrase strand transfer inhibitors, or virological failure.

KEYWORDS:

• HIV
• antiretroviral regimen
• single-tablet regimen
• virological suppression
• protease inhibitor

Article highlights

• DRV/COBI/FTC/TAF is a PI-based regimen formulated as a fixed dose combination approved by FDA for the treatment of HIV infection of adults and pediatric patients weighing at least 40 kg and by EMA for people aged 12 years and older with body weight at least 40 kg.

• Phase III trials conducted on ART-naïve and -experienced participants have reported high rates of virological suppression in people receiving DRV/COBI/FTC/TAF both at weeks 48 and 96; these data have also been published from a study investigating DRV/COBI/FTC/TAF in the context of a test-and-treat strategy. Moreover, no DRV, primary PI, or tenofovir RAMs emerged in participants who experienced VF, identifying DRV/COBI/FTC/TAF as one of the regimen with a higher genetic barrier to resistance.

• DRV/COBI/FTC/TAF has also demonstrated to be well tolerated: in fact, clinical trials recorded a low number of both study discontinuations and grade 3–4 drug-related AEs. Studies comparing DRV/COBI/FTC/TAF with TDF-containing regimen described an improvement in renal and BMD parameters in patients who switched to DRV/COBI/FTC/TAF and an increase in fasting lipid values in participants receiving the study regimen.

• Real-world data observed rates of GI events in PLWH treated with DRV/COBI/FTC/TAF similar to those described with INSTI-based regimens. Switching from an INSTI-based regimen to DRV/COBI/FTC/TAF leads to a significant reduction of NSs.

• International guidelines recommend DRV/COBI/FTC/TAF as alternative regimen for treatment-naïve PLWH and highlight its resistance profile for treatment-experienced individuals; however, the introduction of newer drugs, INSTIs, and innovative strategies, such as long-acting therapy, have limited the role of DRV/COBI/FTC/TAF in the management of HIV infection.

Scientific accuracy check

Janssen provided a scientific accuracy review at the request of the journal editor.

Declaration of interest

A Castagna has received consultancy fees from Gilead Sciences, ViiV Healthcare, Janssen-Cilag and Merck Sharp and Dohme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript discloses research grants from Gilead, ViiV Healthcare via their institution in the past 3 years. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.