Human immunodeficiency virus proviral DNA from peripheral blood and lymph nodes demonstrates concordant resistance mutations to zidovudine (codon 215) and didanosine (codon 74). Division of AIDS Treatment Research Initiative 003 Study Group.
Genotypes that confer drug resistance were evaluated in human immunodeficiency virus (HIV) proviral DNA obtained from peripheral blood mononuclear cells (PBMC) and lymphoid tissue at baseline and after 8 weeks of therapy with zidovudine alone or in combination with didanosine from 22 patients (8 zidovudine-naive and 14 zidovudine-experienced). There was evidence of zidovudine resistance at codon 215 in 27.3% (6/22) of patients. All 20 patients evaluable for codon 74 (site of didanosine resistance) had virus that remained wild type during the 8-week study period. When HIV proviral DNA from PBMC was compared with that from lymphoid tissue, 94.7% (18/19) of evaluable samples were concordant at codon 215 at baseline, while 85.7% (12/14) were concordant at week 8. Resistance in PBMC (but not in lymphoid tissue) developed in 1 of 8 zidovudine-naive patients; an increased proportion of resistant strains in PBMC (but not in lymphoid tissue) was observed in 2 of 14 zidovudine-experienced patients. These results suggest high concordance for drug resistance mutations in HIV proviral DNA from blood and lymph node tissue.
Mayers
D
D
Naval Medical Research Institute and Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. dmayers@pasteur.hjf.org
Bethel
J
J
Wainberg
M A
MA
Weislow
O
O
Schnittman
S
S
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003062:Codon; D004279:DNA, Viral; D016049:Didanosine / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology*; D008297:Male; D017354:Point Mutation; D011533:Proviruses / Q000187:drug effects / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D003062:Codon; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D016049:Didanosine