title: Emergence of drug resistance mutations in a group of HIV-infected children taking nelfinavir-containing regimens.
abstract: HIV-1-infected children are often treated with therapy regimens including protease inhibitors (PIs). We monitored the virologic response in a small group of pediatric patients undergoing therapy with regimens including the PI nelfinavir and determined whether new drug resistance mutations were present immediately after virologic failure. Seventeen reverse transcriptase inhibitor (RTI)-experienced children starting nelfinavir-containing therapy regimens were studied. After virologic failure, HIV-1 protease (PR) and RT sequences were examined for drug resistance mutations. Viral load levels decreased to <400 HIV RNA copies/ml in six patients and remained at <400 HIV RNA copies/ml in four patients. Three patients did not respond virologically; all three had mutations specific for one or more of their regimen drugs either 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 mutations specific for one or more of their regimen drugs after virologic rebound. PI resistance mutations occurred in eight patients: D30N in six, and L90M in three. In three patients, the only new mutation after failure was the RT mutation M184V. Despite virologic failure, sustained increases in CD4+ lymphocyte counts were noted in eight patients. We conclude that in this small group of pediatric patients, virologic failure occurred in all patients whose viral loads did not become undetectable after the switch to a nelfinavir-containing regimen. After failure, new drug resistance mutations were found in either PR or RT. Studies of larger cohorts are warranted to determine whether HIV-1 genotypic data can help in the formulation of effective salvage therapies in children.
authors.affiliation: Division of Allergy, Immunology, and Infectious Diseases, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. fitzg@umdnj.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Fitzgibbon
authors.forename: S
authors.initials: S
authors.lastname: Gaur
authors.forename: S M
authors.initials: SM
authors.lastname: Walsman
authors.forename: M
authors.initials: M
authors.lastname: Janahi
authors.forename: P
authors.initials: P
authors.lastname: Whitley-Williams
authors.forename: J F
authors.initials: JF
authors.lastname: John
mesh_terms: D018791:CD4 Lymphocyte Count; D002986:Clinical Trials as Topic; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005838:Genotype; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D009154:Mutation; D019888:Nelfinavir / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D012194:RNA-Directed DNA Polymerase; D019888:Nelfinavir