Zidovudine resistance and HIV-1 disease progression during antiretroviral therapy

Richard T. D'Aquila*, Victoria A. Johnson, Seth L. Welles, Anthony J. Japour, Daniel R. Kuritzkes, Victor DeGruttola, Patricia S. Reichelderfer, Robert W. Coombs, Clyde S. Crumpacker, James O. Kahn, Douglas D. Richman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

239 Scopus citations

Abstract

Objective: To evaluate the association between resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine and clinical progression. Design: Retrospective analysis of specimens from patients in the AIDS Clinical Trials Group (ACTG) protocol 116B/117, a randomized comparison of didanosine with continued zidovudine therapy in patients with advanced HIV-1 disease who had received 16 weeks or more of previous zidovudine therapy. Setting: Participating ACTG virology laboratories. Patients: 187 patients with baseline HIV-1 isolates. Measurements: Zidovudine susceptibility testing and assays for syncytium-inducing phenotype were done on baseline HIV-1 isolates. Relative hazards for clinical progression or death associated with baseline clinical, virologic, and immunologic factors were determined from Cox proportional hazards regression models. Results: Compared with other patients, 15% (26 of 170) with isolates showing high-level zidovudine resistance (50% inhibitory zidovudine concentration ≥ 1.0 μM) had 1.74 times the risk for progressing to a new AIDS-defining event or death (95% CI, 1.00 to 3.03) and 2.78 times the risk for death (CI, 1.21 to 6.39) in analyses that controlled for baseline CD4+ T-lymphocyte count, syncytium- inducing HIV-1 phenotype, disease stage, and randomized treatment assignment. The clinical benefit of didanosine was not limited to patients with highly zidovudine-resistant baseline HIV-1 isolates. Conclusions: High-level resistance of HIV-1 to zidovudine predicted more rapid clinical progression and death when adjusted for other factors. However, patients with advanced HIV-1 disease may benefit from a change in monotherapy from zidovudine to didanosine whether high-level HIV-1 resistance to zidovudine is present or absent, and laboratory assessment of zidovudine resistance is not necessary for deciding when to switch monotherapy from zidovudine to didanosine.

Original languageEnglish (US)
Pages (from-to)401-408
Number of pages8
JournalAnnals of internal medicine
Volume122
Issue number6
DOIs
StatePublished - Mar 15 1995

ASJC Scopus subject areas

  • Internal Medicine

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