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. 2011:5:44-50.
doi: 10.2174/1874613601105010044. Epub 2011 Apr 22.

A Multicenter, Open Labeled, Randomized, Phase III Study Comparing Lopinavir/Ritonavir Plus Atazanavir to Lopinavir/Ritonavir Plus Zidovudine and Lamivudine in Naive HIV-1-Infected Patients: 48-Week Analysis of the LORAN Trial

K U Ulbricht  1 , G M Behrens, M Stoll, B Salzberger, H Jessen, A B Jessen, B Kuhlmann, H Heiken, A Trein, R E Schmidt
Affiliations

A Multicenter, Open Labeled, Randomized, Phase III Study Comparing Lopinavir/Ritonavir Plus Atazanavir to Lopinavir/Ritonavir Plus Zidovudine and Lamivudine in Naive HIV-1-Infected Patients: 48-Week Analysis of the LORAN Trial

K U Ulbricht et al. Open AIDS J. 2011.

Abstract

Objective: The primary aim of the study was to compare the metabolic side effects of a nucleoside analogue-containing regimen with a nucleoside analogue-sparing double protease inhibitor regimen. A secondary goal was to test for efficacy of a double-PI regimen.

Design: Multicenter, randomized, open-label, phase III clinical trial.

Subjects: Adult HIV-1-infected individuals naïve to antiretroviral therapy with viral load above 400 HIV-RNA copies/ml were randomized (1:1) to either 400 mg lopinavir /100 mg ritonavir (LPV/r) BID plus 150 mg lamivudine/300 mg zidovudine (CBV) BID versus LPV/r BID plus 300 mg atazanavir (ATV) QD. Main outcome measure was the virologic failure in both groups, defined as viral load ≥50 copies/ml at week 48.

Results: In the CBV/LPV/r-arm, 29 out of 35 patients [(83%; 95% confidence interval (CI) 66.9-92.2%] and 18 out of 40 patients (45%; 95% CI 29.7-61.5%) in the ATV/LPV/r-arm had a HIV-RNA level <50 copies/ml at week 48. The intent-to-treat analysis revealed inferior virologic response in the ATV/LPV/r arm (Chi-Q and Fisher´s Exact Test p<0.001) and resulted in premature termination of the trial. Eleven patients in the ATV/LPV/r-arm discontinued therapy because of virological failure. These failures mostly presented with low level replication (<1,000 copies/ml). Increases in CD4 cell counts was significantly more rapid in the ATV/LPV/r arm (p=0.02), but comparable at week 48.

Conclusions: ATV/LPV/r had less virologic efficacy than the conventional RTI-based regimen and resulted in a high virological failure rate with low level replication.

Keywords: HIV-therapy; Therapy-naïve patients.; double-protease-inhibitor.

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Figures

Fig. (1)
Fig. (1)
Virologic response. Virologic response as percentage of all HIV-1-infected patients with a viral load below 50 copies HIV-RNA/mL plasma after enrolment into LORAN study (“intend-to-treat” analysis, top panel) and in all patients receiving antiretroviral therapy in both arms (“observed data” analysis, bottom panel).
Fig. (2)
Fig. (2)
Immunologic response. Time course of mean (SEM) CD4 cell counts (top panel) and mean (SEM) change in CD4 cell counts from baseline (buttom panel) in both treatment arms.
See this image and copyright information in PMC

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