Drug Resistance Mutations Among HIV-1 Strains From Antiretroviral-Naive Patients in Martinique, French West Indies

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Abstract
Summary: We report on the frequency of genetic mutations associated with drug resistance in antiretroviral treatment-naive patients from Martinique (French West Indies), where zidovudine (ZDV) has been available since 1987 and where combination therapy developed simultaneously with its use in continental France. Genotypic resistance was studied in plasma HIV RNA from samples collected between 1988 and 1998 from 70 antiretroviral-naive study subjects, half presenting with either primary infection or documented seroconversion. A line probe assay (LIPA) was used to detect substitutions on the reverse transcriptase (RT) codons 41, 69, 70, 74, 184, and 215. Direct sequencing was used to complete the data for RT codons which were uninterpretable by LIPA. Of these patients, 17 harbored mutated viruses with one or more mutations in the RT gene codons analyzed. ZDV resistance mutations T215Y/F, M41L, and K70R were found in 2, 5, and 12 individuals, respectively. Mutant strains L74V (didanosine [ddI] and dideoxycytidine [ddC]) were detected in 3 patients and M184V (lamivudine/ddI/ddC) in 4 patients. However, pure mutant results at one or more codons of interest were observed in only 5 (7%; 95% confidence interval [CI], 1%-13%) patients, all involving ZDV resistance. One carried both mutations T215Y and M41L known to confer a high degree of phenotypic resistance to ZDV. Among a subgroup of 28 patients with a timepoint of infection after 1995, 24 [86%; ˜95% CI, 73%-99%) presented with a wild-type pattern. The significance of the high prevalence of mixed patterns observed in drug-naive patients remains unclear. However, the frequency of primary mutant genotypes associated with high levels of drug resistance is low in Martinique and in this study we did not observe any currently increased tendency in this frequency.