Drug resistance mutations among HIV-1 strains from antiretroviral-naive patients in Martinique, French West Indies

We report on the frequency of genetic mutations associated with drug resist ance in antiretroviral treatment-naive patients from Martinique (French Wes t Indies), where zidovudine (ZDV) has been available since 1987 and where c ombination therapy developed simultaneously with its use in continental Fra nce. Genotypic resistance was studied in plasma HIV RNA from samples collec ted between 1988 and 1998 from 70 antiretroviral-naive study subjects, half presenting with either primary infection or documented seroconversion. A l ine probe assay (LIPA) was used to detect substitutions on the reverse tran scriptase (RT) codons 41, 69, 70, 74, 184, and 215. Direct sequencing was u sed to complete the data for RT codons which were uninterpretable by LIPA. Of these patients, 17 harbored mutated viruses with one or more mutations i n the RT gene codons analyzed. ZDV resistance mutations T215Y/F, M41L, and K70R were found in 2, 5, and 12 individuals, respectively. Mutant strains L 74V (didanosine [ddI] and dideoxycytidine [ddC]) were detected in 3 patient s and M184V (lamivudine/ddI/ddC) in 4 patients. However, pure mutant result s at one or more codons of interest were observed in only 5 (7%; 95% confid ence interval [CI], 1%-13%) patients, all involving ZDV resistance. One car ried both mutations T215Y and M41L known to confer a high degree of phenoty pic resistance to ZDV. Among a subgroup of 28 patients with a timepoint of infection after 1995, 24 [86%; similar to 95% CI, 73%-99%) presented with a wild-type pattern. The significance of the high prevalence of mixed patter ns 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 inc reased tendency in this frequency.