HIV-1 REVERSE-TRANSCRIPTASE CODON-215 MUTATION IN PLASMA RNA - IMMUNOLOGICAL AND VIROLOGICAL RESPONSES TO ZIDOVUDINE

Treatment of HIV infection with zidovudine (ZDV) may select for change s in the genetic sequence of the viral reverse transcriptase (RT) that imparts drug resistance. The presence of a 2-bp mutation at codon 215 of RT (from threonine to phenylalanine or tyrosine) was assessed in p lasma viral RNA in 85 subjects treated with ZDV in the AIDS Clinical T rials Group (ACTG) 175 virology substudy. Median CD4 cell numbers, HIV plasma RNA levels, and infectious titers of virus were significantly different over 56 weeks of treatment among 58 subjects with the wild-t ype threonine at codon 215 virus at study entry compared with the 27 s ubjects with mutations to phenylalanine or tyrosine (MUT) virus. Thirt y percent (13 of 44 subjects) with wild-type virus at study entry deve loped a new codon 215 mutation. Genotypic resistance at codon 215 in p lasma HIV RNA is associated with the subsequent immunologic and virolo gic failure of ZDV monotherapy in subjects with 200 to 500 CD4 cells/m m(3).