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Elvitegravir Noninferior to Raltegravir at Week 96 in Treatment-Experienced
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XIX International AIDS Conference, July 22-27, 2012, Washington, DC
Mark Mascolini
Elvitegravir plus a ritonavir-boosted protease inhibitor (PI) and one other antiretroviral was noninferior to raltegravir with the same other drugs through 96 weeks in antiretroviral-experienced adults, according to results of an international, double-blind, active-controlled trial [1]. Adverse event rates were similar with the two regimens, except for a lower rate of liver enzyme elevations in the elvitegravir arm.
Elvitegravir, an integrase inhibitor coformulated with the booster cobicistat and tenofovir/emtricitabine, may also be boosted by ritonavir in people taking a ritonavir-boosted PI. This trial enrolled antiretroviral-experienced people with resistance to antiretrovirals in two classes or at least 6 months of experience with two classes. Everyone had a viral load at or above 1000 copies, and study participants could have any CD4 count.
Researchers randomized participants to once-daily elvitegravir or twice-daily raltegravir, each with an active ritonavir-boosted PI and one other antiretroviral. More than half of study participants added darunavir/ritonavir to their integrase inhibitor, while about 20% added lopinavir/ritonavir.
At week 48 a time-to-loss-of-virologic-response (TLOVR) analysis determined that elvitegravir was noninferior to raltegravir, which was the trial's primary endpoint (59% of 351 assigned to elvitegravir and 58% of 351 assigned raltegravir below 50 copies, difference 1.1%, 95% confidence interval -6.0 to 8.2) [2]. At the International AIDS Conference, researchers presented blinded 96-week results.
The safety analysis included all 712 randomized and treated people, while 10 were excluded from the efficacy analysis because of protocol violations. Age averaged 44 in the elvitegravir group and 45 in the raltegravir group; 17% and 19% were women; about two thirds were white and one third black. Median initial viral load was 4.35 log10 copies/mL in the elvitegravir group and 4.42 log10 copies/mL in the raltegravir group. Respective median CD4 counts were 227 and 215.
Through 96 weeks 41% in the elvitegravir arm and 42% in the raltegravir arm had discontinued study drugs. Lack of efficacy explained 17% of discontinuations with elvitegravir and 21% with raltegravir.
The week-96 TLOVR analysis determined sub-50-copy virologic response rates of 47.6% with elvitegravir and 45.0% with raltegravir, a result confirming the noninferiority of elvitegravir (difference 2.6%, 95% CI -4.6 to 9.9). Week-96 response rates were similar with elvitegravir and raltegravir in a missing-data-equals-failure analysis (53.6% and 56.4%) and a missing-data-excluded analysis (79.0% and 83.2%). The virologic failure rate was marginally lower with elvitegravir than with raltegravir.
Major integrase mutations emerged in 6.6% in the elvitegravir arm and 7.4% in the raltegravir arm. Rates of emerging mutations conferring resistance to other classes were low and similar in the two study arms: 3% for any nucleoside mutation, 1% for any protease inhibitor mutation, and 2% to 3% for any nonnucleoside mutation.
Similar proportions of people randomized to elvitegravir and raltegravir had a serious adverse event (20.1% and 23.5%) or a grade 3 or 4 adverse event (24.3% and 23.7%). Grade 3 or 4 AST or ALT elevations were less common with elvitegravir than with raltegravir (2.3% versus 5.9% for AST, 1.7% versus 5.3% for ALT).
References
1. Elion R, Molina JM, Arribas-Lopez JR, et al. Efficacy and safety results from a randomized, double blind, active controlled trial of elvitegravir (once-daily) versus raltegravir (twice-daily) in treatment-experienced HIV-positive patients: long term 96-week data. XIX International AIDS Conference. July 22-27, 2012. Abstract TUAB0105.
2. Molina JM, LaMarca A, Andrade-Villanueva J, et al. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect Dis. 2012;12:27-35. http://www.natap.org/2011/HIV/PIIS1473309911702493.pdf
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