title: 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.
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.
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Damien V
authors.initials: DV
authors.lastname: Cordery
authors.affiliation: Head of Medical Affairs, HIV, Infectious Diseases and Immuneinflammatory Diseases, GlaxoSmithKline, Rio de Janeiro, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Zajdenverg
authors.affiliation: HIV-NAT, Thai Red Cross AIDS Research Centre; and Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.affiliation: Epimed GmbH, Vivantes Auguste-Viktoria Hospital, Berlin, Germany.
authors.forename: Keikawus
authors.initials: K
authors.lastname: Arastéh
authors.affiliation: Department of Internal Medicine, Infectiology and Pulmonology, Humboldt University, Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bergmann
authors.affiliation: Instituto A Z de Pesquisa E Ensino, Pesquisa E Ensino, Brazil.
authors.forename: José L de Andrade
authors.initials: JL
authors.lastname: Neto
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Scherer
authors.affiliation: Boehringer Ingelheim GmbH, Ingelheim, Germany.
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Chaves
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Robinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D018450:Disease Progression; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000145:classification / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D061466:Lopinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011753:Pyrones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides; D000068698:Tenofovir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D061466:Lopinavir; D019259:Lamivudine; D000068698:Tenofovir; D019438:Ritonavir; C107201:tipranavir