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Comparable Efficacy With QUAD, Atripla, ATV/r in Younger and Older Groups
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ICAAC: Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Demonstrates Comparable Efficacy and Favorable Tolerability to Efavirenz/Emtricitabine/Tenofovir DF and to Ritonavir-boosted Atazanavir plus Emtricitabine/Tenofovir DF in Patients ≥50 Years
http://www.natap.org/2012/ICAAC/ICAAC_18.htm
3rd International Workshop on HIV and Aging November 5-6,
2012
Baltimore MD
3rd International Workshop on HIV and Aging, November 5-6, 2012, Baltimore
Mark Mascolini
QUAD (elvitegravir/cobicistat plus tenofovir/emtricitabine [TDF/FTC]) controlled HIV in people 50 and older as well as in younger participants enrolled in two phase 3 trials comparing the once-daily pill to Atripla (efavirenz plus TDF/FTC) or atazanavir/ritonavir plus TDF/FTC [1]. Rates of certain side effects were lower with QUAD than with the comparison regimens in both older and younger people.
QUAD became the first integrase inhibitor-based once-daily coformulated antiretroviral regimen when it proved noninferior to Atripla in study 102 [2] and to atazanavir/ritonavir in study 103 [3] in antiretroviral-naive people. To assess relative efficacy and safety of QUAD and the other regimens in trial participants under 50 or 50 and older, the investigators conducted this analysis of 701 people randomized to QUAD in the two trials, 352 randomized to Atripla, and 356 randomized to boosted atazanavir.
Across the four study arms, about 15% of participants were 50 or older and about 90% men. Slightly more than 80% in both trials had asymptomatic HIV infection, with average CD4 counts in the high 300s. One third in the QUAD-Atripla study had a pretreatment viral load above 100,000 copies, as did 40% in the QUAD-atazanavir trial. Similar proportions randomized to QUAD or Atripla were black (30% and 26%), while the proportion of blacks was higher in the QUAD group than atazanavir group in study 103 (20% versus 13%).
FDA snapshot analyses determined that 48-week sub-50-copy response rates varied little with age or treatment assignment in either study 102 or study 103:
Proportions with 48-week viral load below 50 copies:
-- QUAD 50 or older: 86%
-- Atripla 50 or older: 82%
-- QUAD under 50: 88%
-- Atripla under 50: 84%
-- QUAD 50 or older: 94%
-- Atazanavir 50 or older: 88%
-- QUAD under 50: 89%
-- Atazanavir under 50: 87%
Average CD4 counts climbed significantly more with QUAD than with Atripla through 48 weeks in people under 50 (246 versus 208, P = 0.007), a difference seen in prior trials comparing efavirenz with other antiretrovirals. CD4 gains were somewhat lower in 50-or-older trial participants than in younger people and did not differ between arms (199 QUAD, 194 Atripla). In study 103 CD4 counts also climbed marginally more in younger people (212 QUAD, 213 atazanavir) than in older people (176 QUAD, 200 atazanavir).
Treatment-emergent adverse events leading to discontinuation by week 48 occurred in higher proportions of 50-and-older participants (6% QUAD, 11% Atripla) than in younger participants (3% QUAD, 4% Atripla). In this study, treatment-emergent diarrhea affected about 20% under 50 years old taking either regimen and 20% of older people taking Atripla, but only 8% of older people taking QUAD. While one quarter of younger people and one third of older people reported abnormal dreams in the Atripla arm, about 15% of younger and older people in the QUAD arm had that complaint. The same trend held true for dizziness and rash.
In the QUAD-atazanavir trial, about 5% of participants in the two treatment arms stopped therapy because of treatment-emergent adverse events, and those rates did not vary substantially by age. Ocular icterus affected more people randomized to atazanavir (15% younger, 8% older) than people randomized to QUAD (1% younger, 0 older).
Serum creatinine stayed flat through 48 weeks in younger and older people randomized to Atripla in study 102, while jumping modestly in the first weeks of treatment then staying stable through 48 weeks in people randomized to QUAD. Probably because both cobicistat and ritonavir decrease tubular secretion of creatinine, levels of creatinine rose moderately in both treatment arms in the first weeks of study 103 and remained stable at that level through 48 weeks.
Lipids climbed modestly in all treatment arms in these two trials. In study 103, median triglycerides rose significantly more with QUAD (about 25 mg/dL younger, about 10 mg/dL older) than with atazanavir, and this was the only significant lipid difference between arms (P = 0.001 in both age groups).
References
1. Gallant J, Hardy D, Robbins W, et al. Elvitegravir/cobicistat/ emtricitabine/tenofovir DF demonstrates comparable efficacy and favorable tolerability to efavirenz/emtricitabine/tenofovir DF and to ritonavir-boosted atazanavir plus emtricitabine/tenofovir DF in patients ≥50 years. 3rd International Workshop on HIV and Aging. November 5-6, 2012, Baltimore. Abstract O_17.
2. Sax PE, DeJesus E, Mills A, et al; GS-US-236-0102 study team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012;379:2439-2448. Erratum in Lancet. 2012;380:730.
3. DeJesus E, Rockstroh JK, Henry K, et al; GS-236-0103 Study Team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012;379:2429-2438.
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