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Quantitation of zidovudine (AZT) -resistant HIV-1 in the blood of treated and untreated patients.




 

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



 




Information in this article was accurate in December 30, 1990. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.