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Quantitation of zidovudine (AZT) -resistant HIV-1 in the blood of treated and untreated patients.
Mohri H; Ching WT; Chang HE; Alam H; Ho DD; Cedars-Sinai Medical Center
December 30, 1990
Int Conf AIDS. 1990 Jun 20-23;6(3):116 (abstract no. S.B.81). Unique

OBJECTIVE: To detect, quantify, and characterize AZT-resistant HIV-1 in infected persons. METHODS: End-point-dilution cultures of 15 patients' plasma and peripheral blood mononuclear cells (PBMC) were performed in the presence of 0, 1, 5, & 25 uM of AZT. RESULTS: Of the 15 patients (3 asymptomatic, 5 ARC, 7 AIDS), 10 were treated with AZT and 5 were never treated. Two of the untreated patient had HIV-1 resistant to 25 uM AZT, while 3 other untreated patients had only AZT-sensitive HIV-1. All 10 treated patients had detectable levels of HIV-1 which were resistant to 1 uM AZT. Of these, 6 had highly resistant (5-25 uM) HIV-1 and 4 had moderately resistant (1 uM) virus. Of the 6 patients with rapidly progressive disease, 4 were found to harbor highly AZT-resistant HIV-1. Overall, the infectious titer of HIV-1 resistant to 5-25 uM AZT ranged from 0 to 100 tissue-culture infective dose (TCID) per ml of plasma and from 10 to 1000 TCID per 10(6) PBMC. In several patients, 100% of their total HIV-1 burden in plasma of PBMC were AZT-resistant (5-25 uM). CONCLUSION: An assay to quantify AZT-resistant HIV-1 in vivo has been developed. Its application has revealed that resistant viruses can be recovered from patients never exposed to AZT. In addition, all AZT-treated patients were found to have at least some resistant HIV-1. The level of AZT-resistant HIV-1 can be high (100 TCID/ml in plasma and 1000 TCID/10(6) PBMC) and can represent up to 100% of the total infectious titer in blood. Similar analysis on additional patients, characterization of AZT-resistant viruses in vitro, and studies on the effect of dideoxyinosine on resistant virus in vivo will be presented.

Acquired Immunodeficiency Syndrome/*DRUG THERAPY AIDS-Related Complex/DRUG THERAPY Cells, Cultured Drug Resistance, Microbial Human HIV-1/*DRUG EFFECTS Leukocytes, Mononuclear/DRUG EFFECTS/MICROBIOLOGY Zidovudine/*BLOOD/THERAPEUTIC USE ABSTRACT