Reverse transcriptase mutations in HIV-1-infected children treated with zidovudine.
Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutations were detected in DNA from peripheral blood mononuclear cells from 11 of 12 HIV-1-infected children after 11-20 months of zidovudine monotherapy. The number of children with mutations detected at each codon were as follows: codon 41, 4; codon 67, 2; codon 70, 7; codon 215, 7; codon 219, 0. Codon 41 mutations were found only in the presence of a codon 215 mutation and in the absence of a codon 70 mutation. The codon 41/215 mutant combination was associated with decline in weight-for-age z score during therapy, weight < 10th percentile, CD4+ cell counts < 3rd percentile, and immune-complex dissociated HIV-1 p24 antigen (ICD p24 Ag) levels > 100 pg/ml. Patients developing the codon 70 mutation tended to have body weight > 30th percentile, CD4+ cell counts > 25th percentile, and ICD p24 Ag < 100 pg/ml. The codon 41 mutation was associated with clinical deterioration during a 6-month followup period.
Unal
A
A
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, FL 33101, USA.
Lorenzo
E
E
Brown
M
M
Smith
L
L
Matsuura
S
S
Scott
G
G
Scott
W
W
D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001835:Body Weight; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000032:analysis / Q000187:drug effects; D005260:Female; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000187:drug effects* / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D007223:Infant; D008297:Male; D016296:Mutagenesis / Q000187:drug effects*; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D003062:Codon; D016655:HIV Core Protein p24; D015215:Zidovudine; D054303:HIV Reverse Transcriptase