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Sustained Viral Control With Switch to E/C/F/TAF Plus DRV in Experienced
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IDSA/IDWeek 2015, October 7-11, San Diego
Mark Mascolini
Antiretroviral-experienced people switching from a multipill darunavir/ritonavir regimen to two pills--darunavir plus E/C/F/TAF--maintained viral control for 48 weeks and had improved proteinuria markers in a 135-person randomized trial [1]. No drug-related serious adverse events developed in either study arm.
Tenofovir alafenamide (TAF), a tenofovir prodrug, has been coformulated with elvitegravir, cobicistat, and emtricitabine in a once-daily pill (E/C/F/TAF) that proved virologically noninferior to E/C/F/TDF (tenofovir disoproxil fumarate) in antiretroviral-naive people, but with less frequent signals of kidney or bone toxicity [2]. A multicenter US team conducted a new trial to assess the efficacy and safety of switching to E/C/F/TAF plus darunavir by people with multidrug-resistant HIV.
Study participants had a viral load below 50 copies for at least 4 months while taking a darunavir-containing regimen. Everyone had 2 antiretroviral regimen failures and at least 2-class resistance (possibly including the TDF-related K65R mutation and 3 or fewer thymidine analog mutations). No one had darunavir resistance mutations. Researchers randomized 89 people to once-daily E/C/F/TAF plus 800 mg of darunavir and 46 people to continue their darunavir-containing baseline regimen. The primary endpoint was the proportion of participants with a viral load below 50 copies at week 24 by the FDA snapshot analysis.
Median age stood at 49 in the E/C/F/TAF group and 47 in the control arm. Respective proportions of men were 82% and 61% and of blacks 39% and 57%. Before randomization all study participants were taking a median of 5 pills daily, and two thirds were taking a twice-daily or more frequent regimen. About half in both study arms were taking the integrase inhibitor raltegravir, more than half in each arm were taking TDF, and baseline resistance was similar in the two arms.
After 24 weeks 86 of 89 people randomized to E/C/F/TAF plus darunavir and 42 of 46 randomized to continue their baseline regimen had a viral load below 50 copies (97% versus 91%, difference 5.3%, 95% confidence interval -3.4% to 17.4%, P = 0.23). Two people with virologic failure in the E/C/F/TAF arm had a sub-50-copy viral load at week 36 or week 48. No resistance mutations emerged in the E/C/F/TAF arm, whereas 1 person who continued the baseline regimen acquired the M184V and K65R mutations. After 48 weeks a significantly higher proportion of people randomized to E/C/F/TAF plus darunavir had a viral load below 20 copies (90% versus 72%, P = 0.012).
In both treatment arms, 13% had a grade 3 or 4 adverse event, but only 1% randomized to E/C/F/TAF plus darunavir and no one randomized to continue their baseline regimen had a grade 3 or 4 study drug-related adverse event. No one in either arm had a drug-related serious adverse event or stopped drugs because of an adverse event.
Three urine protein signals, including two markers of tubular proteinuria (RBP:Cr and Beta-2M:Cr), declined significantly in people randomized to E/C/F/TAF plus darunavir while rising slightly in people who continued their baseline darunavir regimen. A score indicating participant satisfaction with their regimen improved significantly more at 24 and 48 weeks in the E/C/F/TAF plus darunavir arm than in the control arm (P < 0.001 for both).
The researchers proposed that, for people with 2-class or greater resistance on a multipill regimen, switching to E/C/F/TAF plus darunavir "provides a simple, once-daily, two-pill option with superior efficacy and comparable tolerability."
References
1. Huhn G, Tebas P, Gallant J, et al. Strategic simplification: the efficacy and safety of switching to elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide (E/C/F/TAF) plus darunavir (DRV) in treatment-experienced HIV-1 infected adults (NCT01968551). IDWeek 2015, October 7-11, San Diego. Abstract 726.
2. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015;385:2606-2615.
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