title: Resistance mutations to zidovudine and saquinavir in patients receiving zidovudine plus saquinavir or zidovudine and zalcitabine plus saquinavir in AIDS clinical trials group 229.
abstract: The relationships among treatment regimens, plasma human immunodeficiency virus (HIV) RNA levels, and resistance mutations to saquinavir (codons 48 and 90) and zidovudine (codon 215) were examined in a cohort of 144 patients from the AIDS Clinical Trials Group 229 study. After 24-40 weeks of therapy, no patients who had received the two-drug combination (zidovudine plus saquinavir) had only codon 48 mutations, 45.8% had only codon 90 mutations, and 8.3% had both codon 48 and 90 mutations. Mutations developed by patients who had received the three-drug combination (zidovudine and zalcitabine plus saquinavir) were codon 48 alone in 1.4%, codon 90 alone in 33.3%, and both codons 48 and 90 in 4.2%. The difference between the groups showed a trend toward reduced mutations with three versus two drugs but did not reach significance (P=.11, two-sided chi2). Higher baseline HIV RNA levels correlated with the development of protease mutations. Mutations at codon 215 were present in 82% of all patients at baseline and in 87% after therapy.
authors.affiliation: Division of Infectious Diseases, Stanford University School of Medicine, California, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Schapiro
authors.forename: J
authors.initials: J
authors.lastname: Lawrence
authors.forename: R
authors.initials: R
authors.lastname: Speck
authors.forename: M A
authors.initials: MA
authors.lastname: Winters
authors.forename: B
authors.initials: B
authors.lastname: Efron
authors.forename: R W
authors.initials: RW
authors.lastname: Coombs
authors.forename: A C
authors.initials: AC
authors.lastname: Collier
authors.forename: T C
authors.initials: TC
authors.lastname: Merigan
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology*; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D016333:HIV Protease / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D019258:Saquinavir / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D016047:Zalcitabine / Q000008:administration & dosage / Q000627:therapeutic use; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D003062:Codon; D012367:RNA, Viral; D015215:Zidovudine; D016047:Zalcitabine; D016333:HIV Protease; D019258:Saquinavir