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

HG Sprenger; N Langebeek; PGH Mulder; CHH ten Napel; R Vriesendorp; AIM Hoepelman; JC Legrand; PP Koopmans; B Bravenboer; RW ten Kate; PHP Groeneveld; WFW Bierman; TS van der Werf; EH Gisolf; C Richter

Disclosures

HIV Medicine. 2015;16(2):122-131. 

In This Article

Abstract and Introduction

Abstract

Objectives 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).

Methods An open-label, noninferiority study was carried out. Antiretroviral therapy (ART)-naïve patients with CD4 count ≤ 350 cells/μL and HIV-1 RNA > 30 000 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).

Results 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.

Conclusions 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.

Introduction

Combination antiretroviral therapy (cART) only consisting of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) is not recommended as first-line treatment for HIV infections.[1]

Antiretroviral regimens frequently have to be adjusted because of toxicity, drug–drug interactions or pregnancy. Our hypothesis was that a triple NRTI regimen can be used safely as a maintenance regimen after successful virological suppression with standard cART. This study was initiated at a time when preferred regimens were still complex with a high pill burden and with more concerns about toxicity resulting in, for example, lipodystrophy.

Initial studies addressing the effect of a switch to triple NRTIs included patients that had not been ART-naïve from the start, resulting in suboptimal responses.[2–6] Subsequent studies exploring the induction-maintenance concept in ART-naïve patients demonstrated noninferiority for triple NRTI regimens compared with two-class triple (or quadruple) cART.[7–11] Some of these studies were not entirely prospective,[7,10] or did not have a comparative design for the maintenance phase.[12] Other studies showed treatment failures because of drug intolerance.[9,11,12]

Here we describe the final results of a randomized, prospective, 96-week study in ART-naïve patients using protease inhibitor (PI)-based triple cART as induction therapy, followed by maintenance with abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) in those who reached an undetectable plasma HIV-1 RNA level (< 50 HIV-1 RNA copies/mL). Our objective was to evaluate noninferiority of ABC/3TC/ZDV compared with continued cART with lopinavir/ritonavir (LPV/r). We were also interested in the metabolic effects of the switch. Interim results at week 48 showed that virological success rates with the triple NRTI regimen and the PI-based cART regimen were similar.[13]

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