Quantitation of zidovudine-resistant human immunodeficiency virus type 1 in the blood of treated and untreated patients.
A nonselective ex vivo assay was used to directly detect and quantify zidovudine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) in the blood of treated and untreated patients. In contrast to previous reports, drug-resistant virus was detected in peripheral blood mononuclear cells of a few of the patients who had never received AZT. The AZT resistance of HIV-1 isolates from one untreated individual was confirmed by further susceptibility studies in vitro and by the finding of a characteristic mutation (Lys-->Arg at codon 70) in the reverse transcriptase. In patients who were clinically stable while on AZT, HIV-1 titers in plasma and mononuclear cells were generally low but resistant viruses already predominated. In those individuals who were deteriorating despite AZT administration, high levels of viremia were observed, and the resistance phenotype was nearly universal. These findings serve to emphasize the magnitude of the AZT-resistance problem in patients on drug treatment.
Mohri
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Aaron Diamond AIDS Research Center, Department of Medicine and Microbiology, New York University School of Medicine, NY 10016.
Singh
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MK
Ching
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WT
Ho
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D000386:AIDS-Related Complex / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D000595:Amino Acid Sequence; D004352:Drug Resistance, Microbial; D005260:Female; D054303:HIV Reverse Transcriptase; D006679:HIV Seropositivity / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D015215:Zidovudine / Q000494:pharmacology* / Q000627:therapeutic use*
D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase