The FDA approved the first darunavir-based single-tablet regimen for the treatment of HIV in July 2018. How is it working out for patients and providers alike?
The US Food and Drug Administration (FDA) approved the first darunavir-based single-tablet regimen (STR) for the treatment of HIV in July 2018. Now, nearly a year since its launch, health care practitioners and patients alike are evaluating its place in the HIV treatment landscape.
Based on the EMERALD and AMBER trials, the FDA approved the combination darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (D/C/F/TAF, Symtuza, Janssen) for the treatment of HIV in treatment-naïve and certain virologically suppressed adults. The 2 phase 3 studies assessed the safety and efficacy of the regimen, and the 48-week DIAMOND study results which were released in April demonstrated its efficacy as a rapid initiation option.
Providers have praised the convenience of D/C/F/TAF for patients but have also noted certain disadvantages.
“As the first and only single-tablet regimen containing a protease inhibitor (PI), [D/C/F/TAF] is a nice option to consolidate therapy for patients already receiving protease inhibitor-based, multi-tablet regimens,” Jason Schafer, PharmD, associate professor of pharmacy practice at Thomas Jefferson University in Philadelphia and the HIV/AIDS section editor for Contagion®, said.
“Darunavir (the PI in [D/C/F/TAF]) has a high barrier to resistance and may be better tolerated than other PIs, but because it is boosted by cobicistat it is subject to many drug-drug interactions,” he continued. “Also, in comparison first line regimens containing integrase inhibitors, PI-containing regimens are less well tolerated, have more drug interactions, and may lead to more treatment discontinuations.”
Eric S. Daar, MD, chief of the Division of HIV Medicine at Harbor-UCLA Medical Center and professor of medicine at the David Geffen School of Medicine at UCLA, also mentioned the convenience of the formulation for patients.
"It basically adds convenience to therapy for those who are on boosted PIs; however, it does not change any of the other properties of this class of drug," he said. "In other words, the availability of this regimen does not markedly change where boosted PIs fit into care, but enhance convenience for those who choose to use this class of drugs."
Melanie Nicol, PharmD, PhD, assistant professor, University of Minnesota College of Pharmacy, also flagged the possibility of drug-drug interactions.
"For those who cannot tolerate integrase inhibitors (generally preferred option these days) this would be a good option as darunavir is also well-tolerated with a high barrier to resistance," she told Contagion®. "Because it contains the PK booster cobicistat, it would be preferable to avoid in someone who may have drug-drug interactions."
Paul Sax, MD, clinical director of the Division of Infectious Disease at the Brigham & Women’s Hospital in Boston, Massachusetts, and a professor of medicine at the Harvard Medical School, similarly noted the convenience of the formulation, but expressed concerns regarding its relevance in an ever-evolving treatment landscape.
“Coformulations like [D/C/F/TAF] are more convenient for patients, and some data support better adherence and outcomes. However, the dominant driver of whether they will be used in place of the separate tablets is coverage by payers,” he told Contagion®.
“For this particular example, HIV treatments are moving away from regimens that require either protease inhibitors (PI) or a [pharmacokinetic] booster, and of course [D/C/F/TAF] has both,” Sax, who is a member of the Contagion® Editorial Advisory Board, continued. “Nonetheless, for those patients who need to be on a boosted PI, [D/C/F/TAF] is clearly a convenient option.”
The oral darunavir-based STR should be taken once daily with food. The drug is not recommended for patients with creatine clearance below 30 mL per minute or those with severe hepatic impairment. Prior to initiating the regimen, patients should be tested for hepatitis B virus infection and renal function should be monitored during therapy.