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Atazanavir Effective After Atazanavir/Ritonavir Induction in Naive Patients
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5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town
Mark Mascolini
Dropping the ritonavir boost from an atazanavir regimen maintained virologic suppression in a large open-label randomized trial reported on the last day of the 5th IAS conference [1]. Forty-eight weeks after randomization, lipid profiles were somewhat better in the unboosted-atazanavir group, but overall side effect rates were similar in the two groups.
ARIES trial investigators enrolled 515 previously untreated people who started atazanavir/ritonavir with abacavir plus lamivudine or emtricitabine. Everyone tested negative for the HLA-B*5701 allele, the abacavir hypersensitivity reaction marker. After 36 weeks, the researchers randomized people with a viral load under 50 copies to continue boosted atazanavir (n = 209) or to raise the atazanavir dose to 400 mg once daily and drop ritonavir (n = 210) for another 48 weeks.
Pretreatment variables were similar in the two study groups, with age averaging 39 years and viral load 5.05 log copies/mL (over 100,000 copies). Researchers stratified participants into groups with a pretreatment load below 100,000 copies (46%) or above that mark (53%). Overall median CD4 count stood at 200, and 13% of enrollees began treatment with fewer than 50 CD4s. Most study participants (84%) were men, and 5% had HCV infection. Significantly more people randomized to unboosted atazanavir than boosted atazanavir had CDC class C HIV infection when the trial began: 34 (16%) versus 17 (8%).
Overall, 90% of study participants completed 48 weeks of randomization, with no difference between study arms. While 2 (1%) withdrew from the unboosted arm because of adverse events, 5 (2%) dropped out of the boosted arm for that reason. Dropouts because of nonadherence numbered 3 in the unboosted group and 4 in the boosted group.
A time-to-loss-of-virologic-response analysis at week 84 (48 weeks after randomization) determined that 86% in the atazanavir-only group (181 of 210) and 81% in the atazanavir/ritonavir group (169 of 209) maintained a viral load below 50 copies (P = 0.140). This result established the noninferiority of unboosted atazanavir versus continued boosted atazanavir. Response rates were similar in people who started the trial with a viral load below 100,000 copies (85% unboosted, 79% boosted) or above 100,000 copies (87% unboosted, 82% boosted).
One person in the unboosted atazanavir group and 7 in the boosted group met the study definition of virologic failure--a confirmed rebound above 400 copies. Because adherence was excellent in both study groups, investigator Kathleen Squires (Thomas Jefferson University, Philadelphia) did not think spotty pill taking in the boosted group explains the higher failure rate.
No major protease inhibitor mutations emerged in any of the 8 people with confirmed virologic failure. In the 1 person whose unboosted atazanavir failed, the M184V lamivudine resistance mutation evolved.
CD4 gains were similar in the two treatment arms. While 63 people (30%) in the unboosted-atazanavir group had a grade 2 to 4 adverse event, 70 (33%) in the boosted arm had a grade 2 to 4 adverse event. Bilirubin levels fell in the unboosted group.
Median changes in fasting lipids from week 36 to week 84 generally favored unboosted atazanavir over boosted atazanavir: total cholesterol -14 versus +6 mg/dL; "good" high-density lipoprotein cholesterol +1 versus +2 mg/dL; "bad" low-density lipoprotein cholesterol -5 versus +4 mg/dL; and triglycerides -34 versus -4 mg/dL. At week 84, median triglycerides in the boosted group lay above a National Cholesterol Education Program target of 150 mg/dL, but below that level in the unboosted group.
Reference
1. Squires K, Young B, DeJesus E, et al. Similar efficacy and tolerability of atazanavir (ATV) compared to ATV/ritonavir (RTV, r), each in combination with abacavir/lamivudine (ABC/3TC), after initial suppression with ABC/3TC + ATV/r in HIV-1 infected patients: 84 week results of the ARIES trial. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract WELBB103.
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