 |
|
|
| |
Elvitegravir-Containing Quad Noninferior to Atazanavir Regimen at 48 Weeks
|
| |
| |
19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
CROI: Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF "Quad" Compared to Ritonavir-boosted Atazanavir plus Emtricitabine/Tenofovir DF in Treatment Naive HIV-1 Infected Subjects - (03/9/11)
CROI: The Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF ("Quad") Compared to Efavirenz/Emtricitabine/Tenofovir DF in Treatment Na•ve HIV-1 Infected Subjects: Primary Results of Study GS-US-236-0102 - (03/8/11)
Mark Mascolini
Quad, the once-daily single-tablet regimen containing the experimental integrase inhibitor elvitegravir, proved virologically noninferior to atazanavir/ritonavir plus tenofovir/emtricitabine (TDF/FTC) in a 48-week double-blind, double-dummy trial that enrolled antiretroviral-naive people [1]. Among people whose regimen failed, 5 of 12 in the Quad group and none of 8 in the atazanavir group had detectable resistance mutations. Both regimens had good safety profiles, though triglycerides rose significantly more in the atazanavir group and creatinine significantly more in the Quad group.
Quad contains elvitegravir plus the boosting agent cobicistat and TDF/FTC. This international trial enrolled 700 antiretroviral-naive people with virus genotypically sensitive to atazanavir, TDF, and FTC, a viral load above 5000 copies, and an estimated glomerular filtration rate at or above 70 mL/min. Researchers randomized them to Quad or to once-daily atazanavir/ritonavir plus TDF/FTC.
Age averaged 38 in the Quad group and 39 in the atazanavir group. About 90% overall were men, and about one quarter were nonwhite. Median pretreatment viral load stood at about 4.9 log10 copies/mL in both study groups, and high proportions (43% randomized to Quad and 40% randomized to atazanavir) had a pretreatment viral load above 100,000 copies. While 35% of enrollees had a CD4 count between 201 and 350, 35% had a count between 351 and 500.
Thirty-three of 353 people (9%) discontinued treatment in the Quad arm, as did 40 of 355 (11%) in the atazanavir arm. Adverse events accounted for discontinuation in 13 people randomized to Quad and 18 randomized to atazanavir. Lack of efficacy accounted for 4 discontinuations in the Quad group and 1 in the atazanavir group.
An FDA snapshot analysis determined sub-50-copy 48-week response rates of 90% with Quad and 87% with atazanavir, a result establishing the virologic noninferiority of Quad in previously untreated people. A missing-data-equals-failure analysis determined sub-50-copy rates of 92% with Quad and 88% with atazanavir. Among people with a pretreatment viral load above 100,000 copies, 50-copy response rates were 85% with Quad and 82% with atazanavir; respective response rates in those starting treatment with at CD4 count at or below 350 were 89% and 88%. CD4 counts rose by an average 207 with Quad and 211 with atazanavir.
Among 12 people analyzed for resistance in the Quad group, 5 had detectable mutations, including a primary integrase mutation in 4, the FTC-related M184V/I in 4, and the TDF-related K65R in 1. None of 8 people analyzed for resistance in the atazanavir arm had detectable mutations.
Grade 3 or 4 adverse events arose in 13% assigned to Quad and 14% assigned to atazanavir. Respective rates of drug-related adverse events were 45% and 57%. Only 1% in either arm had serious drug-related adverse events. Common adverse events did not differ between arms; the most frequent was diarrhea in 22% randomized to Quad and 27% randomized to atazanavir.
Grade 3 or 4 lab abnormalities were generally rare and similar in the two studies arms. Exceptions included hyperbilirubinemia, which affected 58% taking atazanavir and 1% taking Quad. Serum creatinine change from baseline was significantly greater with Quad than with atazanavir at 48 weeks (median 0.12 versus 0.08 mg/dL, P < 0.001). Cholesterol changes were modest and equivalent in the two study groups, but triglyceride median change from baseline was significantly greater with atazanavir (23 versus 8 mg/dL, P = 0.006).
A similar trial (reviewed separately by NATAP) found Quad noninferior to coformulated efavirenz/TDF/FTC at 48 weeks [2].
References
1. DeJesus E, Rockstroh J, Henry K, et al. week 48 results of an ongoing global phase 3 study comparing elvitegravir/cobicistat/emtricitabine/tenofovir (quad) with atazanavir/ritonavir plus emtricitabine/tenofovir in treatment-naive HIV-1+ subjects showing efficacy, safety, and pharmacokinetics. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 627.
2. Sax P, DeJesus E, Mills A, et al. Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate has non-inferior efficacy and favorable safety compared to efavirenz/emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV-1+ subjects. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 101. http://www.natap.org/2012/CROI/croi_25.htm.
|
| |
|
|
|
|
|
