title: Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy. The RV43 Study Group.
abstract: Human immunodeficiency virus type 1 (HIV-1) isolates resistant to zidovudine (ZDV) have previously been demonstrated to exhibit in vitro cross-resistance to other similar dideoxynucleoside agents which contain a 3'-azido group. However, cross-resistance to didanosine (ddI) or dideoxycytidine (ddC) has been less well documented. ZDV, ddI, and ddC susceptibility data have been collected from clinical HIV-1 isolates obtained by five clinical centers and their respective retrovirology laboratories. All subjects were treated only with ZDV. Clinical HIV-1 isolates were isolated, amplified, and assayed for drug susceptibility in standardized cultures of phytohemagglutinin-stimulated donor peripheral blood mononuclear cells obtained from healthy seronegative donors. All five cohorts showed a correlation between decreased in vitro susceptibility to ZDV and decreased susceptibility to ddI and ddC. For each 10-fold decrease in ZDV susceptibility, an average corresponding decrease of 2.2-fold in ddI susceptibility was observed (129 isolates studied; P < 0.001, Fisher's test of combined significance). Similarly, susceptibility to ddC decreased 2.0-fold for each 10-fold decrease in ZDV susceptibility (82 isolates studied; P < 0.001, Fisher's test of combined significance). These data indicate that a correlation exists between HIV-1 susceptibilities to ZDV and ddI or ddC for clinical HIV-1 isolates.
authors.affiliation: Military Medical Consortium for Applied Retroviral Research, Rockville, Maryland 20850.
authors.forename: D L
authors.initials: DL
authors.lastname: Mayers
authors.forename: A J
authors.initials: AJ
authors.lastname: Japour
authors.forename: J M
authors.initials: JM
authors.lastname: Arduino
authors.forename: S M
authors.initials: SM
authors.lastname: Hammer
authors.forename: R
authors.initials: R
authors.lastname: Reichman
authors.forename: K F
authors.initials: KF
authors.lastname: Wagner
authors.forename: R
authors.initials: R
authors.lastname: Chung
authors.forename: J
authors.initials: J
authors.lastname: Lane
authors.forename: C S
authors.initials: CS
authors.lastname: Crumpacker
authors.forename: G X
authors.initials: GX
authors.lastname: McLeod
mesh_terms: D000386:AIDS-Related Complex / Q000097:blood; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood; D016049:Didanosine / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D006679:HIV Seropositivity / Q000097:blood; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D013997:Time Factors; D016047:Zalcitabine / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
chemical_list: D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine