Salvage therapy with atazanavir/ritonavir combined to tenofovir in HIV-infected patients with multiple treatment failures : randomized ANRS 107 trial

• Published in: Antiviral therapy 2006-01, Vol.11 (2), p.213-221
• Main Authors: PIKETTY, Christophe, GERARD, Laurence, GIRARD, Pierre-Marie, CHAZALLON, Corine, MARCELIN, Anne-Geneviève, CLAVEL, Francois, TABURET, Anne-Marie, CALVEZ, Vincent, MADELAINE-CHOMBRIN, Isabelle, MOLINA, Jean-Michel, ABOULKER, Jean-Pierre
• Format: Article
• Language: English
• Subjects: Adenine - adverse effects; Adenine - analogs & derivatives; Adenine - therapeutic use; Adult; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Atazanavir Sulfate; Biological and medical sciences; Drug Resistance, Viral; Female; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Middle Aged; Mutation; Oligopeptides - adverse effects; Oligopeptides - therapeutic use; Organophosphonates - adverse effects; Organophosphonates - therapeutic use; Pharmacology. Drug treatments; Pyridines - adverse effects; Pyridines - therapeutic use; Ritonavir - adverse effects; Ritonavir - therapeutic use; Salvage Therapy; Tenofovir; Treatment Failure; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350601100213

Ritonavir (RTV)-boosted atazanavir (ATV) and tenofovir disoproxil fumarate (TDF-DF) are promising in highly experienced patients because of their pharmacokinetic profile, activity, safety and resistance properties. A 26-week study of the safety and efficacy of RTV-boosted ATV plus TDF-DF was conducted in 53 HIV-infected patients who were failing their current highly active antiretroviral therapy (HAART) regimen. Patients with history of failure to at least two protease inhibitors (PIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) were randomized to either continue their current regimen (group 1) or replace the PI by ATV (300 mg once daily) boosted by RTV (100 mg; group 2) for 2 weeks. Then, all patients received the same combination of ATV, RTV and TDF-DF (300 mg) plus optimized NRTIs regimen. At baseline, median CD4+ T-cell count was 206/mm3, median viral load (VL) 5.0 log10/ml and median numbers of NRTI, NNRTI and PI resistance mutations were 7, 1 and 8, respectively. At week 2, median VL remained unchanged from baseline in group 2 as compared with group 1 (-0.1 vs -0.1 log10/ml). At week 26, a mild decrease in median VL from baseline of 0.2 log10/ml was observed, with 16 (31%) and 9 (17%) patients exhibiting a decrease in viral load of at least 0.5 and 1.0 log10/ml, respectively. Baseline phenotypic and genotypic resistance to ATV were the most predictive independent factors of virological response. The regimen was well tolerated. In these very advanced patients failing highly HAART, the combination of boosted ATV plus TDF-DF yielded low antiretroviral activity.