Polymorphism and drug-selected mutations in the reverse transcriptase gene of HIV-2 from patients living in southeastern France

Few data are available about the susceptibility and the genotypic resistance pattern of human immunodeficiency virus type 2 (HIV-2) to nucleoside reverse transcriptase inhibitors (NRTIs). The HIV-2 reverse transcriptase (RT) gene from 25 HIV-2-infected patients followed-up in Marseilles and the surrounding area was analyzed. The aims of this study were to characterize the polymorphism of HIV-2 RT in the absence of drug, to determine whether it naturally harbors codons associated with drug-resistance in HIV-1, and to identify mutations emerging under NRTI-selective pressure. Fourteen patients had never undergone antiretroviral therapy and 11 received NRTI. Seventy sequences were analyzed. In untreated patients, 12 spots of high natural polymorphism (at positions 10, 11, 20, 43, 104, 121, 135, 162, 176, 180, 200, and 227) were observed; 4 of them were specific of HIV-2 (10, 176, 180, 227). Moreover, results showed four positions that could be associated with natural resistance to NRTI (75I, 118I, 219E, and perhaps 215S), in addition to those described previously for non-nucleoside reverse transcriptase inhibitors (NNRTIs) (181I, 188L, 190A). In HIV-2-infected patients receiving NRTI-containing therapies, specific genotypic patterns were observed with a high frequency of mutation Q151M (in 45% of patients) often associated with 70R, 115F, 214L, and/or 223R, which might compose an HIV-2 multi-NRTI resistance complex. Four newly or rarely described NRTI-selected mutations were observed: I5V, K35R, F214L, and K223R. As in HIV-1, substitution M184V was found in 3TC-treated patients. In conclusion, these findings highlight the need for specific guidelines for determining genotypic resistance and treatment of HIV-2.