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 Ulbricht1, §, G.M Behrens1, §, M Stoll1, B Salzberger2, H Jessen3, A.B Jessen3, B Kuhlmann4, H Heiken4, A Trein5, R.E Schmidt*, 1
1 Department for Clinical Immunology and Rheumatology, Hannover Medical School, Hannover, Germany
2 Department for Internal Medicine I, University Hospital Regensburg, Germany
3 Private Practice, Berlin, Germany
4 Private Practice, Hannover, Germany
5 Private Practice, Stuttgart, Germany


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© Ulbricht et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department for Clinical Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg- Str. 1, D-30625 Hannover, Germany; Tel: ++49 511 532 6656; Fax: ++49 511 532 9067; E-mail: immunologie@mh-hannover.de
§ These authors contributed equally to the manuscript.


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, double-protease-inhibitor, Therapy-naïve patients..