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Atazanavir Without Ritonavir Sustains
Virologic Suppression 120 Weeks in ARIES
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ICAAC: Induction/Maintenance-Simplification: Sustained Virologic Efficacy of Atazanavir (ATV) Versus Atazanavir/Ritonavir (ATV/r), each in Combination with Abacavir/Lamivudine (ABC/3TC) over 120 Weeks: the ARIES Trial - (09/15/10)
50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 12-15, 2010, Boston
Mark Mascolini
After 120 weeks in an extended phase of the ARIES trial, unboosted atazanavir maintained viral suppression as well as atazanavir/ritonavir (both with abacavir/lamivudine) [1]. Sub-50-copy response rates at week 120 figured by a time-to-loss-of-virologic response (TLOVR) analysis exceeded 80% in both treatment arms. Drug-related adverse events were less common with unboosted atazanavir.
Antiretroviral-naive people began treatment in ARIES with atazanavir/ritonavir plus abacavir/lamivudine [2]. People with a confirmed viral load below 50 copies at week 36 were randomized to stop ritonavir (n = 210) or to continue boosted atazanavir (n = 209). At week 84, 181 of 210 (86%) people assigned to unboosted atazanavir and 169 of 209 (81%) taking atazanavir/ritonavir maintained a viral load below 50 copies, a result establishing the noninferiority of unboosted atazanavir [2].
People who completed 84 weeks of treatment were eligible to continue their assigned regimen through 144 weeks. This extension phase included 189 people in the unboosted atazanavir group and 180 in the boosted group. At ICAAC the investigators presented results through week 120. People who entered the extension phase were similar demographically to the full randomized group, with an average age of 39 years and median pretreatment viral load and CD4 count of 5.06 log and 198 cells About 55% in each arm had a pretreatment load above 100,000 copies. Most study participants (85%) were men, and 64% were white.
Between week 84 and week 120, 17 people (9%) withdrew from the unboosted arm and 14 (8%) dropped out of the boosted arm. Two people taking unboosted atazanavir and one taking boosted atazanavir stopped treatment because of virologic failure, defined as a confirmed viral load above 400 copies. An additional patient taking boosted atazanavir quit because of "insufficient viral load response." One person taking unboosted atazanavir and 2 taking boosted atazanavir dropped out because of adverse events.
In the primary TLOVR analysis at week 120, 158 of 189 people taking unboosted atazanavir (84%) and 150 of 180 taking boosted atazanavir (83%) maintained a viral load below 50 copies. Response rates were similarly high among people who entered the trial with a viral load above 100,000 copies: 85 of 104 (82%) on unboosted atazanavir and 85 of 101 (84%) on boosted atazanavir. There were 3 virologic failures (2%) between weeks 84 and 120 in the unboosted group and 4 (2%) in the boosted group. Treatment-related mutations (M184V, T215F, and the protease mutation N88S) emerged in only 1 patient, who was taking boosted atazanavir. Median CD4 gains through week 120 were the same in each treatment arm: 290 cells.
Treatment-emergent grade 2 to 4 adverse events between weeks 36 and 120 developed in 23 people taking unboosted atazanavir (12%) and 38 taking boosted atazanavir (21%). During this period, high bilirubin was measured in 12 people on unboosted atazanavir (6%) and 25 on boosted atazanavir (14%). No new treatment-related serious adverse events emerged between weeks 84 and 120.
The total-to-high-density lipoprotein (HDL) cholesterol ratio was below baseline in both treatment arms at weeks 36, 84, and 120. From week 36 through week 120, the unboosted arm had a significantly greater decline than the boosted arm in total-to-HDL cholesterol ratio (-0.54 versus -0.18, P = 0.0001), total cholesterol (-15 versus -7, P < 0.0001), triglycerides (-38 versus -19, P = 0.0007), and low-density lipoprotein cholesterol (-6 versus +5, P = 0.0001).
References
1. Squires K, DeJesus E, Bellos N, et al. Sustained virologic efficacy of atazanavir versus atazanavir/ritonavir, each in combination with abacavir/lamivudine over 120 weeks: the ARIES trial. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 12-15, 2010. Boston. Abstract H-204.
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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