Document Detail


Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection: a randomized trial.
MedLine Citation:
PMID:  12965939     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Resistance to antiretroviral agents remains a leading cause of treatment failure for patients infected with HIV-1. OBJECTIVE: To describe the efficacy and safety of tenofovir disoproxil fumarate (tenofovir DF) compared with placebo in patients with detectable viral replication despite current antiretroviral therapy. DESIGN: Randomized, double-blind, placebo-controlled study through 24 weeks. After 24 weeks, all patients received open-label tenofovir DF for the remainder of the 48-week study. SETTING: 75 North American, European, and Australian HIV clinics. PATIENTS: 552 HIV-1-infected adults who were receiving antiretroviral therapy and had stable HIV-1 RNA levels ranging from 400 to 10,000 copies/mL. MEASUREMENTS: Change in HIV-1 RNA level (time-weighted average from baseline through week 24); proportion of patients with grade 3 or 4 laboratory abnormalities and adverse events; and genotypic HIV-1 resistance testing in a separate substudy at baseline, week 24, and week 48. RESULTS: A statistically significant decrease in HIV-1 RNA level through week 24 (the primary end point) was observed in the tenofovir DF group versus the placebo group (-0.61 log10 copies/mL vs. -0.03 log10 copies/mL, respectively [P < 0.001]; difference, -0.58 log10 copies/mL [95% CI, -0.68 to -0.49 log10 copies/mL]). In a virologic substudy, 94% of 253 patients had plasma isolates expressing reverse transcriptase mutations associated with nucleoside resistance mutations at baseline. Through week 24, the incidence of clinical adverse events was similar between patients receiving placebo and those receiving tenofovir DF (14% vs. 13%). No evidence of tenofovir DF-related toxicity was seen through week 48. CONCLUSION: In treatment-experienced patients with suboptimal viral suppression, tenofovir DF significantly reduced HIV-1 RNA level and had a safety profile similar to that of placebo.
Authors:
Kathleen Squires; Anton L Pozniak; Gerald Pierone; Corklin R Steinhart; Daniel Berger; Nicholaos C Bellos; Stephen L Becker; Michael Wulfsohn; Michael D Miller; John J Toole; Dion F Coakley; Andrew Cheng;
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Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of internal medicine     Volume:  139     ISSN:  1539-3704     ISO Abbreviation:  Ann. Intern. Med.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-10     Completed Date:  2003-09-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372351     Medline TA:  Ann Intern Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  313-20     Citation Subset:  AIM; IM    
Affiliation:
Keck School of Medicine, University of Southern California, Los Angeles, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenine / adverse effects,  analogs & derivatives*,  therapeutic use*
Adult
Anti-HIV Agents / adverse effects,  therapeutic use*
CD4 Lymphocyte Count
Double-Blind Method
Drug Resistance, Viral
Female
HIV Infections / drug therapy*,  virology
HIV-1 / drug effects*,  genetics
Humans
Male
Mutation
Organophosphorus Compounds / adverse effects,  therapeutic use*
Phosphonic Acids*
Placebos
RNA / blood
Viral Load
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Organophosphorus Compounds; 0/Phosphonic Acids; 0/Placebos; 0/tenofovir disoproxil; 63231-63-0/RNA; 73-24-5/Adenine
Comments/Corrections
Summary for patients in:
Ann Intern Med. 2003 Sep 2;139(5 Pt 1):I22   [PMID:  12965954 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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