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A pilot study of abacavir/lamivudine (ABC/3TC) and raltegravir (RAL) in antiretroviral naive HIV-1 infected subjects: 48-week results
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IAC Vienna 2010 July
B. Young1,2, T. Vanig3, E. DeJesus4, T. Hawkins5, L. Yau6, B. Ha6, SHIELD Study Team
1Univ of Colorado, Denver, United States, 2Health Connections International, Amsterdam, Netherlands, 3Spectrum Med. Group, Phoenix, United States, 4Orlando Immunology Ctr, Orlando, United States, 5Southwest CARE Ctr, Santa Fe, United States, 6GlaxoSmithKline, RTP, United States
Background: RAL is a HIV-1 integrase strand-transfer inhibitor with potent in vitro activity that has not been evaluated with ABC/3TC in antiretroviral naïve HIV-1 infected individuals. The objective of the SHIELD study was to evaluate the efficacy and safety of ABC/3TC+RAL as initial therapy.
Methods: This is a 96-week, open-label, pilot, prospective, multicenter study evaluating ABC/3TC (600 mg/300 mg once-daily)+RAL (400 mg twice daily) in subjects with entry viral load (VL) >1,000 c/mL. Subjects were excluded if they were HLA-B*5701 positive or had RAL, ABC, or 3TC resistance mutations. Virologic failure (VF) was defined as failure to achieve VL< 400 c/mL by Wk 24 or confirmed rebound ≥400 c/mL or confirmed 1 log10 c/mL increase above nadir. The planned Week 48 interim analysis is reported.
Results: SHIELD enrolled 35 subjects. Baseline (BL) characteristics were: median HIV-RNA 4.8 log10 c/mL (34% ≥100,000 c/mL), median CD4+ 301 cells/mm3 (20% < 200 cells/mm3). Two subjects (6%) prematurely discontinued study by Week 48: adverse event (1) and lost-to-followup (1).
At Week 48, the proportion of subjects with HIV-1 RNA < 400 and < 50 c/mL were both 91% (32/35) by ITT M=F. Median CD4+ change from BL was 247 cells/mm3. One subject met VF criteria. Five subjects (14%) had drug-related grade 2-4 adverse events. No drug-related SAEs were reported.
Week 48 fasting lipid changes [median (95% confidence intervals)] were not different from BL for total/HDL cholesterol [0.01 (-0.23, 0.46)], triglycerides [-1 (-11.5, 58.5)] mg/dL, and increased for LDL cholesterol [9 (3.5, 17)] mg/dL, HDL cholesterol [5.5 (2-8)] mg/dL, and total cholesterol [16.5 (11-29.5)] mg/dL.
Conclusions: In this pilot study, RAL+ABC/3TC achieved sustained virologic suppression and exhibited potent antiretroviral activity through Week 48, with limited impact on fasting lipids.
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