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A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96-week results from the FREE study.

HIV medicine (2014-12-05)
H G Sprenger, N Langebeek, P G H Mulder, C H H Ten Napel, R Vriesendorp, A I M Hoepelman, J C Legrand, P P Koopmans, B Bravenboer, R W Ten Kate, Php Groeneveld, Wfw Bierman, Ts van der Werf, Eh Gisolf, C Richter
ABSTRACT

The aim of the study was to test the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen, with potential beneficial metabolic effects, as maintenance therapy after induction with dual NRTIs and a boosted protease inhibitor (PI). An open-label, noninferiority study was carried out. Antiretroviral therapy (ART)-naïve patients with CD4 count ≤ 350 cells/μL and HIV-1 RNA >30000 copies/mL (n=207) were treated with zidovudine/lamivudine and lopinavir/ritonavir. After achieving HIV-1 RNA <50 copies/mL on two consecutive occasions between weeks 12 and 24 after baseline, 120 patients (baseline: median HIV-1 RNA 5.19 log10 copies/mL; median CD4 count 180 cells/μL) were randomized to receive abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) (n=61) or to continue the PI-based ART (n=59). For the proportions of patients (intention-to-treat; missing=failure) with HIV-1 RNA <400 copies/mL (PI group, 66%; ABC/3TC/ZDV group, 71%) and <50 copies/mL (PI group, 63%; ABC/3TC/ZDV group, 62%) at 96 weeks, switching to ABC/3TC/ZDV was noninferior compared with continuing the PI regimen; the difference in failure rate (ABC/3TC/ZDV minus PI) was -4.4 percentage points [95% confidence interval (CI) -21.0 to +12.3 percentage points] and +0.4 percentage points (95% CI -16.9 to +17.7 percentage points), respectively. In the per protocol analysis, the difference in virological failure for HIV-1 RNA >400 copies/mL (0 of 39 patients in the PI group and two of 45 patients in the NRTI group) and for HIV-1 RNA >50 copies/mL (two of 39 and three of 45 patients, respectively) was +4.4 percentage points (95% CI -2.1 to +11.0 percentage points) and +1.5 percentage points (95% CI -8.6 to +11.7 percentage points), respectively, also showing noninferiority. Serum lipids significantly improved in the NRTI group, but not in the PI arm. A single-class NRTI regimen after successful induction with standard ART had similar antiviral efficacy compared to continuation of a PI-based regimen at 96 weeks after baseline, with improved serum lipids.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ritonavir, ≥98% (HPLC)
Sigma-Aldrich
3′-Azido-3′-deoxythymidine, ≥98% (HPLC)
Supelco
Zidovudine, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Lamivudine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Lamivudine, ≥98% (HPLC), powder
Ritonavir, European Pharmacopoeia (EP) Reference Standard
USP
Zidovudine, United States Pharmacopeia (USP) Reference Standard
Zidovudine, European Pharmacopoeia (EP) Reference Standard
Lamivudine, European Pharmacopoeia (EP) Reference Standard
Lamivudine for system suitability 2, European Pharmacopoeia (EP) Reference Standard
Lamivudine for system suitability 1, European Pharmacopoeia (EP) Reference Standard
USP
Lamivudine, United States Pharmacopeia (USP) Reference Standard