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Evaluating the proportion of patients with mutated drug-resistant HIV-1 strains is a major issue of current AIDS research and therapy. According to a recent study in the United States, nearly 80% of HIV-1-infected patients have virus strains that are resistant to at least one antiretroviral drug. The aim of this study was to assess the extent of multiple drug resistance among individuals followed for HIV-1 infection in France.We compiled data in a relational database for 3884 reverse transcriptase (2248 patients) and 3915 protease (2194 patients) sequences of plasma samples submitted for testing between January 1997 and March 2002 at the reference HIV AIDS hospitals located in Marseille (France).Genotypic resistance to at least one nucleoside reverse transcriptase inhibitor (NRTI) was present in 78.3%, resistance to at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) was present in 38.9%, and resistance to at least one protease inhibitor (PI) was present in 47.0% of plasma samples. The proportion of patients carrying a virus with multiple resistance to three categories of drugs (at least one NRTI plus at least one NNRTI plus at least one PI) peaked at 25.9% in 2000 and stabilized at 25.5% in March 2002.This study demonstrates the high prevalence of drug-resistant virus in a European cohort of patients currently under treatment for HIV-1 infection. New therapeutic strategies based on a more rational use of genotypic data should be worked out to prevent the development of resistance.