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ACTG 5202: shorter time to virologic failure (VF) with abacavir/lamivudine (ABC/3TC) than tenofovir/emtricitabine (TDF/FTC) as part of combination therapy in treatment-naïve subjects with screening HIV RNA ³100,000 c/mL
Presented by Paul Sax, United States.
P. Sax1, C. Tierney2, A. Collier3, M. Fischl4, C. Godfrey5, N. Jahed6, K. Droll2, L. Peeples2, L. Myers7, G. Thal8, J. Rooney9, B. Ha10, W. Woodward11, E. Daar12
1Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, United States, 2Harvard School of Public Health, Boston, United States, 3University of Washington School of Medicine, Seattle, United States, 4AIDS Clinical Research Unit, University of Miami School of Medicine, Miami, United States, 5National Institute of Allergy and and Infectious Diseases, Division of AIDS, Bethesda, United States, 6ACTG Operations Center, Social & Scientific Systems Inc., Silver Spring, United States, 7Frontier Science & Technology Research Foundation Inc., Amherst, United States, 8Bristol-Myers Squibb, New York, United States, 9Gilead Sciences, Inc., Foster City, United States, 10GlaxoSmithKline, Research Triangle Park, United States, 11Abbott Laboratories, Abbott Park, United States, 12Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, United States
Background: ABC/3TC and TDF/FTC as part of initial HIV treatment are recommended, but comparative data are limited. Planned DSMB review of A5202 resulted in early study changes.
Methods: A5202 is a phase IIIB, randomized 4-arm study for treatment-naïve subjects of double-blind ABC/3TC vs TDF/FTC with open-label efavirenz or atazanavir+ritonavir, stratified by screening HIV RNA (< vs ³100,000 c/mL). Primary endpoints: Time to VF (confirmed RNA ³1000 c/mL at 16-24 weeks or ³200 c/mL at ³24 weeks) and time to first Grade 3/4 adverse event (AE). DSMB review found significant virologic efficacy differences by NRTIs for subjects with screening RNA ³100,000 c/mL, prompting unblinding of NRTIs, additional analyses and recommendations to continue with NRTIs of choice. Data from only the higher RNA stratum by NRTIs are presented; analyses intent-to-treat, regimen change included.
Results: A5202 enrolled 1,858 eligible subjects; 797 had screening RNA ³100,000. Median follow-up was 60 weeks. 85% were men, 26% Black, 25% Hispanic; mean baseline RNA=5.1 log c/mL, CD4=181/mm3. Time to VF was significantly shorter in the ABC/3TC than TDF/FTC arm (HR=2.33, 95% CI 1.46-3.72, p=0.0003), occurring in 57 and 26 subjects respectively (figure). In a secondary cross-sectional analysis (prior VF and regimen changes included), the proportion (95% CI) with HIV RNA <50 c/mL at week 48 was 75% (69%-80%) for ABC/3TC and 80% (74%- 85%) for TDF/FTC (p=0.20). Subjects receiving ABC/3TC had shorter time to grade 3/4 AEs (HR=1.87, 95% CI 1.43-2.43, p<0.0001), predominantly general body aches and lipid increases. Suspected drug hypersensitivity was reported in 7% of each NRTI group.
Conclusions: In subjects entering A5202 with screening HIV RNA ³100,000 c/mL, there was a significantly shorter time to VF and grade 3/4 AEs in subjects randomized to ABC/3TC than TDF/FTC. The comparisons of blinded NRTIs in the lower HIV RNA stratum and each regimen’s third drug in both strata are ongoing.