Emergence of drug resistance mutations in a group of HIV-infected childrentaking nelfinavir-containing regimens

HIV-1-infected children are often treated with therapy regimens including p rotease inhibitors (Pls). We monitored the virologic response in a small gr oup of pediatric patients undergoing therapy with regimens including the PI nelfinavir and determined whether new drug resistance mutations were prese nt immediately after virologic failure. Seventeen reverse transcriptase inh ibitor (RTI)-experienced children starting nelfinavir-containing therapy re gimens were studied. After virologic failure, HIV-1 protease (PR) and RT se quences were examined for drug resistance mutations. Viral load levels decr eased to <400 HIV RNA copies/ml in six patients and remained at <400 HIV RN A copies/ml in four patients. Three patients did not respond virologically; all three had mutations specific for one or more of their regimen drugs ei ther before or soon after nelfinavir initiation. The virologic response was transient in eight patients whose viral loads did not decrease to <400 HIV RNA copies/ml. Genotypic data from seven of the eight patients revealed mu tations specific for one or more of their regimen drugs after virologic reb ound. PI resistance mutations occurred in eight patients: D30N in six, and L90M in three. In three patients, the only new mutation after failure was t he RT mutation M184V. Despite virologic failure, sustained increases in CD4 1 lymphocyte counts were noted in eight patients. We conclude that in this small group of pediatric patients, virologic failure occurred in all patien ts whose viral loads did not become undetectable after the switch to a nelf inavir-containing regimen. After failure, new drug resistance mutations wer e found in either PR or RT. Studies of larger cohorts are warranted to dete rmine whether HIV-1 genotypic data can help in the formulation of effective salvage therapies in children.