title: Reverse transcriptase genotype and antiretroviral susceptibility of human immunodeficiency virus isolates from patients with advanced disease treated with didanosine: correlation with virologic response and survival.
abstract: To identify correlates of virologic response and survival, the reverse transcriptase (RT) genotype and in vitro antiviral susceptibility of human immunodeficiency virus (HIV) isolates from 20 patients treated with didanosine were studied. Patients had advanced HIV disease and were intolerant to or had failed zidovudine. Neither RT genotype nor antiviral susceptibility testing, as determined by a peripheral blood mononuclear cell-based assay, correlated with a virologic response to didanosine, as determined previously by quantitative serum culture. Only one (8%) of 12 isolates obtained after 6-12 months of treatment showed mutation at codon 74 conferring didanosine resistance. Reversions were seen in three of five patients with pre-treatment zidovudine resistance mutations at codons 70, but in none of eight with mutations at codon 215. Pretreatment isolates encoding mutations at RT codon 215 or encoding codon 123 asp were associated with both significantly greater CD4 lymphocyte depletion and shorter survival. In this cohort of patients with advanced HIV disease, neither rapid emergence of didanosine resistance nor rapid reversion of zidovudine resistance was observed. To better understand the relationship between virologic response and in vitro susceptibility to didanosine, more precise tools may be needed.
authors.affiliation: Department of Medicine, North Shore University Hospital, Cornell University Medical College, Manhasset, NY 11030, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Shepp
authors.forename: A
authors.initials: A
authors.lastname: Ashraf
authors.forename: I T
authors.initials: IT
authors.lastname: Tang
authors.forename: M E
authors.initials: ME
authors.lastname: Match
authors.forename: C
authors.initials: C
authors.lastname: Millan
authors.forename: R
authors.initials: R
authors.lastname: Pergolizzi
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016049:Didanosine / Q000627:therapeutic use*; D005838:Genotype; D006678:HIV / Q000187:drug effects / Q000201:enzymology*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D012191:Retroviridae Proteins / Q000235:genetics*; D013534:Survival
chemical_list: D019380:Anti-HIV Agents; D012191:Retroviridae Proteins; D012194:RNA-Directed DNA Polymerase; D016049:Didanosine