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Abstract
A prospective, randomized, Phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection - ACTG 5142
S.A. Riddler1, R. Haubrich2, G. DiRienzo3, L. Peeples3, W.G. Powderly4, K.L. Klingman5, K.W. Garren6, T. George7, J.F. Rooney8, B. Brizz9, D. Havlir10, J.W. Mellors1, AIDS Clinical Trials Group 5142 Study Team
1University of Pittsburgh, Pittsburgh, United States, 2University of California San Diego, San Diego, United States, 3Harvard School of Public Health, Statistical and Data Analysis Center, Boston, United States, 4University College, Dublin, Ireland, 5NIAID, Division of AIDS, Bethesda, Maryland, United States, 6Abbott Laboratories, Abbott Park, Illinois, United States, 7Bristol-Myers Squibb, Plainsboro, New Jersey, United States, 8Gilead Sciences, Foster City, California, United States, 9Social & Scientific Systems, Inc, Silver Spring, Maryland, United States, 10University of California San Francisco, San Francisco, United States
Background: First-line therapy with 2 nucleoside reverse transcriptase inhibitors (2NRTI) and either efavirenz (EFV) or lopinavir/ritonavir (LPV) has not been compared in a randomized trial; and the NRTI-sparing combination of LPV+EFV has not been studied as initial therapy.
Methods: Randomized, open-label, prospective trial comparing three class-sparing regimens for naïve subjects: LPV+EFV (L/E) vs. LPV+2NRTI (LPV; soft-gel BID) vs. EFV+2NRTI (EFV). NRTIs were selected before randomization from ZDV, d4T XR or TDF (each plus 3TC). Primary objectives were to compare between arms the time to confirmed virologic failure (VF; HIV-1 RNA>200 after week 32) and regimen completion (RC; VF or toxicity-related discontinuation of any regimen component). The significance level adjusted for multiple between-arm comparisons and interim analyses was 0.016. Analyses were ITT (censored data not equal to failure).
Results: 753 enrolled subjects (median CD4 182 cells/mm3, median HIV-1 RNA 100,000 copies/mL) were followed for a median 112 weeks. NRTI choice was ZDV 42%, d4T XR 24%, and TDF 34%. No statistically significant between-arm differences were observed in time to VF or RC (p>0.016). However, there was a trend toward shorter time to VF (p=0.033) and RC (p=0.065) for LPV compared with EFV. Kaplan-Meier estimates of the proportions without VF by week 96 were 73%, 67% and 75% for L/E, LPV and EFV arms, respectively. At week 96, the percentages with HIV-1 RNA <50 copies/mL were 83%, 77%, and 89% for the L/E, LPV and EFV arms, respectively (p=0.003 LPV vs. EFV). The median 96 week increase in CD4 was significantly greater for LPV-containing arms (L/E +268, LPV +285 cells/mm3) than for EFV (+239.5; p=0.01). The time to treatment-limiting toxicity was similar for all arms.
Conclusions: Compared with a regimen of EFV+2NRTI, LPV+2NRTI tended to have shorter time to virologic failure and regimen completion. The NRTI-sparing regimen of LPV+EFV had similar efficacy and safety as EFV+2NRTI.
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