Genotypic Determinants of the Virological Response to Tenofovir Disoproxil Fumarate in Nucleoside Reverse Transcriptase Inhibitor-Experienced Patients

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Abstract
Objective: 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. Methods: 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 10 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 ≥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. Conclusion: 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.

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