FREE trial: induction therapy with ART (abacavir/lamivudine/lopinavir/r) followed by maintenance regimen with triple NRTI, compared to continued ART
© Sprenger et al; licensee BioMed Central Ltd. 2008
Published: 10 November 2008
Purpose of the study
To assess the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen as maintenance therapy, after successful induction with a dual NRTI and protease inhibitor (PI) combination.
Randomized, open-label, multicenter, 96-week comparative study. Main inclusion criteria: antiretroviral therapy (ART) naïve patients, CD4 ≤350 cells/μL, HIV-1 RNA concentrations (VL) > 30,000 copies/mL. Exclusion criteria included predefined abnormal values of fasting glucose, triglycerides, LDL-cholesterol or LDL/HDL ratio. Patients were randomized after they had reached VL < 50 c/mL on two consecutive occasions between 12 and 24 weeks after the start of a BID zidovudine/lamivudine and BID lopinavir/ritonavir combination. Eligible subjects switched to abacavir/lamivudine/zidovudine (TZV) bid or continued the PI-containing regimen. Primary end-point at week 96: proportion of subjects with VL < 400 c/mL. Here, we present the 48-week interim data with virological failure VL > 50 c/mL.
Summary of results
207 patients had similar baseline (BL) characteristics: mean age 41 years, 87% male, median CD4 180 cells/mm3 (range 10–440), median VL 155,000 c/mL (900–28300000). A total of 118 subjects (57%) met randomization criteria. Of all BL data, only VL differed significantly between dropouts and randomized subjects (median 253,000 c/mL versus 118,500 c/mL, p = 0.006). After 14 weeks, 21 subjects were randomized, after 20 weeks: 40 subjects, and after 26 weeks: 57 subjects. Sixty subjects were allocated to TZV switch, and 58 subjects to continue NRTIs/PI. At 48 weeks follow-up after BL, there were no significant differences between CD4 cells in the TZV arm (median 340 cells/mm3), and the NRTIs/PI arm (397 cells/mm3). VL results were similar; there were two virological failures (3%) in the TZV group (1,480 person-weeks) and seven (12%) in the NRTIs/PI-group (1,475 person-weeks) after 48 weeks of therapy (Log Rank test; p = 0.13).
TZV as maintenance therapy after induction with NRTIs/PI in previously antiretroviral naïve patients shows an antiviral activity comparable to continuation of a PI-based regimen at 48 weeks interim analysis. Final analysis of the data at week 96 has to be awaited to further evaluate the efficacy of TZV maintenance ART.
This article is published under license to BioMed Central Ltd.