Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients

• Published in: Antiviral therapy 2004-06, Vol.9 (3), p.315-323
• Main Authors: MASQUELIER, Bernard, TAMALET, Catherine, RUFFAULT, Annick, PALMER, Pierre, TRYLESINSKI, Aldo, MILLER, Michael, BRUN-VEZINET, Francoise, COSTAGLIOLA, Dominique, MONTES, Brigitte, DESCAMPS, Diane, PEYTAVIN, Gilles, BOCKET, Laurence, WIRDEN, Marc, IZOPET, Jacques, SCHNEIDER, Véronique, FERRE, Virginie
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - blood; Adenine - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Codon; Cohort Studies; France; Genotype; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - virology; HIV Reverse Transcriptase - antagonists & inhibitors; HIV Reverse Transcriptase - genetics; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; Humans; Medical sciences; Multivariate Analysis; Organophosphonates - blood; Organophosphonates - therapeutic use; Pharmacology. Drug treatments; Point Mutation - drug effects; Reverse Transcriptase Inhibitors - therapeutic use; RNA, Viral - blood; Tenofovir
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350400900303

To assess the genotypic determinants of the virological response to tenofovir disoproxil fumarate (TDF) in a multicentre cohort of antiretroviral (ARV)-experienced patients receiving TDF as a part of a salvage therapy. HIV-1 genotype was assessed at baseline in a subgroup of 161 patients of the French expanded access program receiving a stable TDF-including regimen for 3 months or more. Reverse transcriptase mutations associated with the viral load decrease at month 3 with a P-value or = 6 mutations predicted resistance to TDF with corresponding reductions in viral load of -1.3 +/- 1.1, and +0.1 +/- 0.7 log10 copies/ml, respectively. In patients with a TDF mutation score of 3-5, the decrease in viral load was -0.8 +/- 1.0 log10 copies/ml and was considered possibly resistant. In the multivariate analysis, a TDF mutation score > or = 6, previous use of amprenavir, indinavir and lopinavir, and co-prescription of didanosine were associated with a worse virological response. The bootstrap analysis showed the robustness of the TDF mutation score. In ARV-experienced patients receiving TDF-containing regimens, a score derived from seven reverse transcriptase mutations was shown to be independently predictive of the virological response.