Switching from a suppressive five-drug regimen to fixed-dose elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) plus darunavir (DRV) proved virologically noninferior to maintaining the initial regimen at 24 weeks and virologically superior at 48 weeks. Kidney markers improved in people who changed to the two-pill combination.
The licensing of new antiretrovirals and new antiretroviral classes has improved chances of controlling HIV replication even in people with multidrug-resistant virus. But some salvage regimens include several individual agents, sometimes with dietary restrictions. Once-daily E/C/F/TAF (Genvoya) has been licensed in the United States and the European Union. The once-daily protease inhibitor darunavir (Prezista) can be boosted by ritonavir (Norvir) or cobicistat (Tybost). U.S. and Canadian researchers conducted this open-label randomized trial to test the efficacy and safety of staying with a multidrug suppressive regimen or switching to E/C/F/TAF plus darunavir.
Participants were adults with a viral load below 50 copies/mL for at least four months on their current regimen. All baseline regimens included ritonavir-boosted darunavir. Everyone had virologic failure with at least two antiretroviral regimens and had virus resistant to at least two antiretroviral classes. No one had a history of resistance to integrase inhibitors, but participants could be taking the integrase inhibitor raltegravir (Isentress), elvitegravir (Vitekta) or dolutegravir (Tivicay, DTG). Researchers randomized participants 2:1 to switch to E/C/F/TAF plus darunavir (800 mg) or to maintain their current regimens. The primary efficacy endpoint was percentage with a viral load below 50 copies/mL after 24 weeks by the U.S. Food and Drug Administration snapshot algorithm.
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The 89 participants randomized to E/C/F/TAF plus darunavir and the 46 randomized to continue their baseline regimen were similar in age (median 49 and 47 years), CD4 count (median 519 and 518 cells/mm3), median number of pills in baseline regimen (five and five), proportion with two-class resistance (70% and 74%) and proportion with three-class resistance (26% and 20%). The E/C/F/TAF group included a higher proportion of men (82% versus 61%) and a lower proportion of blacks (39% versus 57%).
At week 24, E/C/F/TAF plus darunavir proved noninferior to the baseline regimen with sub-50-copy rates of 96.6% and 91.3% (difference 5.3%, 95% confidence interval [CI] -3.4% to 17.4%). At week 48, E/C/F/TAF plus darunavir met prespecified criteria for superiority to the baseline regimen with suppression rates of 94.4% versus 76.1% (difference 18.3%, 95% CI 3.5% to 33.0%). The lower 48-week virologic success rate with the baseline regimen reflected a higher rate of virologic failure with the baseline regimen (11% versus 2%) and a higher discontinuation rate (11% versus 2%).
The overall adverse event rate was higher with E/C/F/TAF plus darunavir than with the baseline regimen (92% versus 78%), but no one stopped a study drug because of an adverse event. Rates of grade 3 or 4 lab abnormalities were similar with E/C/F/TAF plus darunavir and the baseline regimen (11% and 9%). Median change in estimated glomerular filtration rate at week 48 did not differ significantly between the two regimens (+7.4 and +3.9 mL/min), but the E/C/F/TAF group had significantly greater declines in quantitative proteinuria (urine protein-to-creatinine ratio) and tubular proteinuria (retinol binding protein-to-creatinine ratio and beta 2 microglobulin-to-creatinine ratio).
Treatment satisfaction scores among participants were significantly higher with E/C/F/TAF plus darunavir than with the baseline regimen at weeks 24 (+28 versus +21) and 48 (+27 versus +20) (P < .001 for both). Participants assigned to E/C/F/TAF plus darunavir reported fewer days with missed doses than did those assigned to maintain the baseline regimen.