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Atazanavir Without Ritonavir as Simpler Maintenance: 144-Week ARIES Results
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6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 17-20, 2011, Rome
Mark Mascolini
After 108 weeks a maintenance combination of unboosted atazanavir plus abacavir/lamivudine (ABC/3TC) controlled HIV as well as standard atazanavir/ritonavir plus ABC/3TC, but with fewer side effects [1]. Both previously untreated groups began therapy with 36 weeks of atazanavir/ritonavir plus ABC/3TC in the multicenter ARIES trial.
Unboosted atazanavir has advantages of simplicity, lower cost, and potentially greater safety. But US adult and adolescent antiretroviral guidelines recommend atazanavir/ritonavir in "preferred" and "alternative" first-line combinations, while giving a nod to unboosted atazanavir only as an "acceptable" first-line alternative. These experts advise prescribing ABC/3TC or zidovudine/3TC with unboosted atazanavir because tenofovir can further lower levels of unboosted atazanavir.
To test the viability of unboosted atazanavir after 36 weeks of atazanavir/ritonavir, US and Canadian investigators planned the ARIES trial, which recruited antiretroviral-naive people with a viral load above 1000 copies, any CD4 count, and a genotype indicating safe use of ABC. After taking atazanavir/ritonavir (300/100 mg once daily) plus ABC/3TC for 36 weeks, participants with a confirmed viral load below 50 copies before week 36, a sub-50 load immediately before week 36, and no protocol-defined virologic failure were randomized to continue that regimen or to stop ritonavir and raise the atazanavir dose to 400 mg once daily.
After 48 weeks, unboosted atazanavir proved noninferior to boosted atazanavir, as 181 of 210 people (86%) in the unboosted group and 169 of 209 (81%) in the boosted group maintained a viral load below 50 copies [2].
ARIES investigators invited people who completed 84 weeks to continue their assigned regimen through week 144. The researchers defined virologic failure after that point as a confirmed viral load at or above 400 copies. Of 379 people invited to continue, 369 (97%) did. Baseline demographics were similar between study groups at week 84 and similar to those in the week-36 randomized population: Age averaged 39 years, 85% of study participants were men, and 64% were white. Pretreatment viral load stood a little above 100,000 copies, and median pretreatment CD4 count was 198.
Of 369 people who entered the extended phase of ARIES, 314 (85%) completed 144 weeks, and the completion rate did not differ between study arms. A time-to-loss-of-virologic-response analysis determined that 77% randomized to unboosted atazanavir and 73% randomized to boosted atazanavir had a viral load under 50 copies at week 144. Proportions with a load under 400 copies were 84% in the unboosted arm and 80% in the boosted arm.
Five people taking unboosted atazanavir and 6 taking boosted atazanavir had a protocol-defined virologic failure. Only one major protease inhibitor mutation, N88S, arose in 1 person, who was taking boosted atazanavir. Median CD4 gains from study entry to week 144 were 305 in the unboosted arm and 302 in the boosted arm.
Rates of grade 2 to 4 adverse events from week 36 through week 144 were lower in the unboosted group (25 events, 13%) than in the boosted group (42 events, 23%). During that period, hyperbilirubinemia (the only treatment-related adverse event with an incidence of 3% or higher) affected 12 people (6%) taking unboosted atazanavir and 25 (14%) taking boosted atazanavir.
Median lipid changes between week 36 and week 144 favored the unboosted group. Triglycerides fell 42 mg/dL with unboosted atazanavir during that period and 11 mg/dL with boosted atazanavir during that period (P < 0.0001).
Total-to-high-density-lipoprotein cholesterol ratio improved significantly more from week 36 to week 144 in the unboosted group (-0.43) than in the boosted group (-0.19) (P = 0.008).
References
1. Squires K, Young B, DeJesus E, et al. Similar efficacy and tolerability of atazanavir (ATV) compared to ATV/ritonavir (RTV), each in combination with abacavir/lamivudine (ABC/3TC), after initial suppression with ABC/3TC + ATV/RTV in HIV-1 infected patients: final (144 weeks) results of the open-label, multicenter, non-inferiority ARIES study. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract MOPE215.
2. Squires KE, Young B, Dejesus E, et al. Similar efficacy and tolerability of atazanavir compared with atazanavir/ritonavir, each with abacavir/lamivudine after initial suppression with abacavir/lamivudine plus ritonavir-boosted atazanavir in HIV-infected patients. AIDS. 2010;24:2019-2027.
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