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