title: Correlation of clinical progression in human immunodeficiency virus-infected children with in vitro zidovudine resistance measured by a direct quantitative peripheral blood lymphocyte assay.
abstract: A rapid method for determination of zidovudine resistance was developed and results were correlated with clinical outcome in human immunodeficiency virus (HIV)-infected children. The zidovudine susceptibilities of HIV-1 isolates from 34 children were determined through a direct quantitative peripheral blood lymphocyte assay and compared with results of the AIDS Clinical Trials Group resistance assay. Patients' peripheral blood lymphocytes were 5-fold diluted and cocultured with donor lymphocytes and varying concentrations of zidovudine. Isolates were defined as sensitive if inhibited by < or = 1.0 microM zidovudine and resistant at > 1.0 microM. Children (n = 21) with zidovudine-resistant virus had greater evidence of disease progression than did those with zidovudine-sensitive virus (n = 11) as demonstrated by failure to thrive (57% vs. 9%, P = .01) and opportunistic infections (48% vs. 0, P = .006). This assay may be useful as a screening tool for development of clinically relevant zidovudine resistance.
authors.affiliation: Department of Pediatrics, UCLA Medical Center 90024-1752, USA.
authors.forename: K
authors.initials: K
authors.lastname: Nielsen
authors.forename: L S
authors.initials: LS
authors.lastname: Wei
authors.forename: M S
authors.initials: MS
authors.lastname: Sim
authors.forename: A
authors.initials: A
authors.lastname: Deveikis
authors.forename: M
authors.initials: M
authors.lastname: Keller
authors.forename: E R
authors.initials: ER
authors.lastname: Stiehm
authors.forename: L M
authors.initials: LM
authors.lastname: Frenkel
authors.forename: Y J
authors.initials: YJ
authors.lastname: Bryson
mesh_terms: D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004352:Drug Resistance, Microbial; D005500:Follow-Up Studies; D006678:HIV / Q000187:drug effects; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000187:drug effects; D008826:Microbial Sensitivity Tests / Q000379:methods*; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016655:HIV Core Protein p24; D015215:Zidovudine