Zidovudine resistance, syncytium-inducing phenotype, and HIV disease progression in a case-control study. The VA Cooperative Study Group.

Published

Journal Article

A case-control study of patients with progressive (cases) or nonprogressive (controls) disease was designed to determine the association among disease progression, zidovudine sensitivity, and syncytium-inducing phenotype. Viral isolates were screened for sensitivity to zidovudine using a peripheral blood mononuclear cell-based assay and for syncytium-inducing (SI) phenotype in MT2 cell culture. Thirty-four patients, whose disease progressed to AIDS or whose CD4 cell numbers fell < 200 cells/mm3, were matched with 34 patients whose conditions had not progressed or whose CD4 cell numbers remained > 200 cells/mm3. Virus was successfully cultured from both the progressor and the nonprogressor in 17 of these 34 matched case-control pairs. In six of the 17 pairs, virus isolated from the progressor had an IC50 (50% inhibitory concentration) for zidovudine > 1 microM and at least threefold greater than the IC50 of virus isolated from the matched nonprogressor (p = 0.04). In 16 of these 17 pairs the virus isolated from the progressor had the SI phenotype, indicative of high cytopathogenicity, while the virus from the matched nonprogressor had a non-syncytium-inducing phenotype (p < 0.0001). Zidovudine therapy did not appear to select for the SI phenotype in this patient population. A statistically significant association between high-level zidovudine resistance and clinical disease progression was demonstrated. A statistically significant association between the SI phenotype and disease progression was demonstrated. The results suggest that disease progression while being treated with zidovudine therapy may be more closely associated with the SI phenotype than with zidovudine resistance.

Full Text

Duke Authors

Cited Authors

  • St Clair, MH; Hartigan, PM; Andrews, JC; Vavro, CL; Simberkoff, MS; Hamilton, JD

Published Date

  • August 1993

Published In

Volume / Issue

  • 6 / 8

Start / End Page

  • 891 - 897

PubMed ID

  • 8315574

Pubmed Central ID

  • 8315574

International Standard Serial Number (ISSN)

  • 0894-9255

Language

  • eng