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Similar efficacy and tolerability of atazanavir (ATV) compared to ATV/ritonavir (RTV, r), each in combination with abacavir/lamivudine (ABC/3TC), after initial supression with ABC/3TC + ATV/r in HIV-1 infected patients: 84 week results of the ARIES trial
Presented by Kathleen Squires (United States), Kathleen Squires (United States).
K. Squires1, B. Young2, E. DeJesus3, N. Bellos4, D. Murphy5, D. Sutherland-Phillips6, H. Zhao6, L. Patel6, L. Ross6, P. Wannamaker6, M. Shaefer6
1Thomas Jefferson University, Philadelphia, United States, 2University of Colorado, Denver, United States, 3Orlando Immunology Center, Orlando, United States, 4SW Infectious Diseases Association, Dallas, United States, 5Clinique Medicale L'Actuel, Montreal, Canada, 6GlaxoSmithKline, Research Triangle Park, United States
Background: Induction with a RTV-boosted PI regimen followed by simplification (without RTV) may offer sustained virologic suppression while minimizing potential long-term adverse effects and costs associated with RTV.
Methods: A large, open-label, multicenter, non-inferiority study. ART-naïve subjects received ABC/3TC + ATV/r followed by randomization (1:1) at Week 36 to maintain or discontinue RTV for an additional 48 weeks. Eligibility for randomization required confirmed vRNA < 50 c/mL and no virologic failure. Protocol-defined VF after Week 36 was confirmed rebound of vRNA ≥400 c/mL. Primary endpoint was proportion of subjects with vRNA < 50 c/mL at Week 84 (TLOVR).
Results: Baseline demographics of the 419 subjects randomized at Week 36: (mean age 39 years; 84% male; 63% white; vRNA 5.05 log10 c/mL; median CD4+ 200 cells/mm3) were similar between arms. 379/419 (90%) completed 84 weeks.
| Week 84 Results, ITT-Exposed Population | ABC/3TC + ATV, N=210 | ABC/3TC + ATV/r, N=209 | p-value | | vRNA <50/400 c/mL, TLOVR, n (%) | 181 (86%)/194 (92%) | 169 (81%)/180 (86%) | *p=0.140/p=0.036 | | BL vRNA <100,000 c/mL | 85%/88% | 79%/84% | na | | BL vRNA ≥100,000 c/mL | 87%/96% | 82%/88% | na | | Protocol defined VF, n (%) | 1 (0.5%) | 7 (3%) | na | | Median CD4+ cell count (ΔBL), cells/mm3 | 240 | 259 | na | | Any Drug-Related Grade 2-4 AE from BL to Week 84, n (%) | 63 (30%) | 70 (33%) | na | | Indiv. AEs in ≥10%
Hyperbilirubinemia | 34 (16%) | 40 (19%) | na | | *p-value from CMH test stratified by baseline viral load strata |
Median changes in fasting lipids from Week 36 to 84 were as follows for the simplification vs. continuation arms, respectively: cholesterol -14 vs. 6 mg/dL; HDL 1 vs. 2 mg/dL; LDL -5 vs. 4 mg/dL; and triglycerides -34 vs. -4 mg/dL.
Conclusions: Similar and sustained efficacy was demonstrated regardless of baseline vRNA in the simplification (ABC/3TC + ATV) and continuation (ABC/3TC + ATV/r) regimens at 84 weeks after achieving virologic suppression on the induction regimen; virologic failure was infrequent (2%).
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