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PLoS One. 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.

Author information

1
The Kirby Institute, University of New South Wales, Sydney, Australia.
2
Head of Medical Affairs, HIV, Infectious Diseases and Immuneinflammatory Diseases, GlaxoSmithKline, Rio de Janeiro, Brazil.
3
HIV-NAT, Thai Red Cross AIDS Research Centre; and Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
4
Epimed GmbH, Vivantes Auguste-Viktoria Hospital, Berlin, Germany.
5
Department of Internal Medicine, Infectiology and Pulmonology, Humboldt University, Berlin, Germany.
6
Instituto A Z de Pesquisa E Ensino, Pesquisa E Ensino, Brazil.
7
Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, United States of America.
8
Boehringer Ingelheim GmbH, Ingelheim, Germany.

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.

PMID:
26730818
PMCID:
PMC4701182
DOI:
10.1371/journal.pone.0144917
[Indexed for MEDLINE]
Free PMC Article

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