Richard T. D'Aquila, MD; Victoria A. Johnson, MD; Seth L. Welles, PhD, ScD; Anthony J. Japour, MD; Daniel R. Kuritzkes, MD; Victor DeGruttola, PhD; Patricia S. Reichelderfer, PhD; Robert W. Coombs, MD, PhD; Clyde S. Crumpacker, MD; James O. Kahn, MD; Douglas D. Richman, MD
D'Aquila RT, Johnson VA, Welles SL, Japour AJ, Kuritzkes DR, DeGruttola V, et al. Zidovudine Resistance and HIV-1 Disease Progression during Antiretroviral Therapy. Ann Intern Med. 1995;122:401-408. doi: 10.7326/0003-4819-122-6-199503150-00001
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Published: Ann Intern Med. 1995;122(6):401-408.
To evaluate the association between resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine and clinical progression.
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.
Participating ACTG virology laboratories.
187 patients with baseline HIV-1 isolates.
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.
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.
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.
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Infectious Disease, HIV.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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