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Randomized Controlled Trial
. 2016 Jan 5;11(1):e0144917.
doi: 10.1371/journal.pone.0144917. eCollection 2016.

Tipranavir/Ritonavir (500/200 mg and 500/100 mg) Was Virologically Non-Inferior to Lopinavir/Ritonavir (400/100 mg) at Week 48 in Treatment-Naïve HIV-1-Infected Patients: A Randomized, Multinational, Multicenter Trial

David A Cooper  1 , Damien V Cordery  1 , Roberto Zajdenverg  2 , Kiat Ruxrungtham  3 , Keikawus Arastéh  4 , Frank Bergmann  5 , José L de Andrade Neto  6 , Joseph Scherer  7 , Ricardo L Chaves  8 , Patrick Robinson  7 ; study team
Collaborators, Affiliations
Randomized Controlled Trial

Tipranavir/Ritonavir (500/200 mg and 500/100 mg) Was Virologically Non-Inferior to Lopinavir/Ritonavir (400/100 mg) at Week 48 in Treatment-Naïve HIV-1-Infected Patients: A Randomized, Multinational, Multicenter Trial

David A Cooper et al. PLoS One. .

Abstract

Ritonavir-boosted tipranavir (TPV/r) was evaluated as initial therapy in treatment-naïve HIV-1-infected patients because of its potency, unique resistance profile, and high genetic barrier. Trial 1182.33, an open-label, randomized trial, compared two TPV/r dose combinations versus ritonavir-boosted lopinavir (LPV/r). Eligible adults, who had no prior antiretroviral therapy were randomized to twice daily (BID) 500/100 mg TPV/r, 500/200 mg TPV/r, or 400/100 mg LPV/r. Each treatment group also received Tenofovir 300 mg + Lamivudine 300 mg QD. The primary endpoint was a confirmed viral load (VL) <50 copies/mL at week 48 without prior antiretroviral regimen changes. Primary analyses examined CD4-adjusted response rates for non-inferiority, using a 15% non-inferiority margin. At week 48, VL<50 copies/mL was 68.4%, 69.9%, and 72.4% in TPV/r100, TPV/r200, and LPV/r groups, respectively, and TPV/r groups showed non-inferiority to LPV/r. Discontinuation due to adverse events was higher in TPV/r100 (10.3%) and TPV/r200 (15.3%) recipients versus LPV/r (3.2%) recipients. The frequency of grade ≥3 transaminase elevations was higher in the TPV/r200 group than the other groups, leading to closure of this group. However, upon continued treatment or following re-introduction after treatment interruption, transaminase elevations returned to grade ≤2 in >65% of patients receiving either TPV/r200 or TPV/r100. The trial was subsequently discontinued; primary objectives were achieved and continuing TPV/r100 was less tolerable than standard of care for initial highly active antiretroviral therapy. All treatment groups had similar 48-week treatment responses. TPV/r100 and TPV/r200 regimens resulted in sustained treatment responses, which were non-inferior to LPV/r at 48 weeks. When compared with the LPV/r regimen and examined in the light of more current regimens, these TPV/r regimens do not appear to be the best options for treatment-naïve patients based on their safety profiles.

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Conflict of interest statement

Competing Interests: This study was funded by Boehringer-Ingelheim. Joseph Scherer is currently an employee of Boehringer-Ingelheim Pharmaceuticals, Inc. Patrick Robinson was an employee of Boehringer-Ingelheim during the conduct of the study and the preparation of the manuscript. Ricardo Chaves was formerly employed with Boehringer-Ingelheim Pharmaceuticals, Inc. Roberto Zajdenverg is employed at GlaxoSmithKline, Brazil. Kiat Ruxrungtham has served as a consultant for Merck, Tibotec, and Mylan. He has been paid for speaking engagements with Bristol-Myers Squibb, Merck, Roche, Jensen-Cilag, GlaxoSmithKline, Thai GPO, and Mylan Lab limited. Keikawus Arastéh was speaker, investigator, and advisor as well as country-coordinating investigator (Tranxition study) for Boehringer-Ingelheim Pharmaceuticals, Inc. Frank Bergmann has received support for travel to meetings for the study by Boehringer-Ingelheim Pharmaceuticals, Inc. There are no patents, products in development, or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Patient disposition up to study closure.
Fig 2
Fig 2. Treatment response up to week 48 (confirmed VL <50 copies/mL).
See this image and copyright information in PMC

References

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