Human immunodeficiency virus reverse transcriptase codon 215 mutations diminish virologic response to didanosine-zidovudine therapy in subjects with non-syncytium-inducing phenotype.
Eight zidovudine-experienced subjects received zidovudine and didanosine for 30 weeks followed by 30 weeks of didanosine monotherapy. At study entry, plasma from 4 subjects had human immunodeficiency virus RNA pol T215Y/F mutant and 4 had codon 215 wild type. All 8 subjects had non-syncytium-inducing virus phenotype. Sustained 10-fold decreases in plasma RNA levels were seen only in subjects who initially had 215 wild type RNA, despite the development of a T215Y/F mutation during combination therapy. Virologic and immunologic benefits were maintained in this group with didanosine monotherapy. No subject developed a pol L74V codon mutation. Significant differences in plasma virus load and CD4 cell responses were seen in this zidovudine-didanosine combination pilot study relative to codon 215 genotype.
Holodniy
M
M
AIDS Research Center, Department of Veterans Affairs Palo Alto Health Care System, CA 94304, USA.
Katzenstein
D
D
Mole
L
L
Winters
M
M
Merigan
T
T
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D003062:Codon; D016049:Didanosine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D015215:Zidovudine / Q000008:administration & dosage*
D019380:Anti-HIV Agents; D003062:Codon; D012367:RNA, Viral; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D016049:Didanosine