title: T69D/N pol mutation, human immunodeficiency virus type 1 RNA levels, and syncytium-inducing phenotype are associated with CD4 cell depletion during didanosine therapy.
abstract: The contribution of virologic and host factors to CD4 cell depletion associated with human immunodeficiency virus (HIV) type 1 was evaluated in children drawn from a larger efficacy trial of 2 doses of didanosine (ddI) monotherapy (Pediatric AIDS Clinical Trials Group 144). Thirty children, half with stable CD4 cell counts (non-progressors) and half with a marked decline in CD4 cells (progressors), were studied during 60-72 weeks of ddI therapy. The children were matched for age and CD4 cell counts at study entry. Three viral parameters, syncytium-inducing phenotype, higher virus load, and mutation in HIV-1 pol encoding the T69D/N mutation, were associated with disease progression. Disease progression was not associated with mutations in the reverse-transcriptase gene previously associated with resistance to ddI (L74V, K65R, or M184V). The selection of the T69D/N mutation in children with HIV-1 disease progression during ddI therapy suggests that this mutation confers a fitness advantage to the virus that may include resistance to ddI.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA, USA.
authors.forename: Willscott E
authors.initials: WE
authors.lastname: Naugler
authors.forename: Florence H
authors.initials: FH
authors.lastname: Yong
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Carey
authors.forename: Joan A
authors.initials: JA
authors.lastname: Dragavon
authors.forename: Robert W
authors.initials: RW
authors.lastname: Coombs
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Frenkel
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D016049:Didanosine / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D015751:Genes, pol; D005838:Genotype; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012367:RNA, Viral / Q000032:analysis*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D016049:Didanosine