Effects of discontinuation of zidovudine treatment on zidovudine sensitivity of human immunodeficiency virus type 1 isolates.

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Effects of discontinuation of zidovudine treatment on zidovudine sensitivity of human immunodeficiency virus type 1 isolates.

Antimicrob Agents Chemother. 1993 Jul;37(7):1525-30. Unique Identifier : AIDSLINE MED/93371049
Boucher CA; van Leeuwen R; Kellam P; Schipper P; Tijnagel J; Lange JM; Larder BA; Department of Virology, University of Amsterdam, Amsterdam, The; Netherlands.

Abstract: Zidovudine treatment of individuals infected with human immunodeficiency virus type 1 (HIV-1) results in HIV-1 isolates with a reduced zidovudine sensitivity in vitro. This reduction is due to mutations causing amino acid substitutions at five codons (41, 67, 70, 215, and 219) on the reverse transcriptase enzyme of HIV. HIV-1 isolates were obtained 8 to 69 weeks after therapy discontinuation from 10 patients at different stages of disease. Zidovudine sensitivity was determined by the HeLa CD4+ plaque assay. The presence of the resistance-conferring mutations was determined by using a selective polymerase chain reaction. Sensitivity could be determined for six isolate pairs: one showed a decline in the 50% inhibitory zidovudine concentration after therapy discontinuation; four pairs did not show a change. The majority of changes in the five codons in isolates from all 10 patients were the result of a relative increase in the wild-type sequence. Complete changes from mutant to the wild type were seen for only two codons in isolates from two patients. This study of isolates from a small group of individuals at different stages of disease, who had been taking zidovudine for 1 to 2 years, shows that a period of 1 year without zidovudine may be required to achieve a change from a mutant or mixed virus population to a wild-type virus population.

Keywords: Cloning, Molecular Codon/GENETICS CD4-Positive T-Lymphocytes/CYTOLOGY/DRUG EFFECTS DNA, Viral/ANALYSIS Genotype Human HIV Core Protein p24/METABOLISM HIV Seropositivity/BLOOD/DRUG THERAPY HIV-1/*DRUG EFFECTS/*GENETICS/PHYSIOLOGY Leukocyte Count/DRUG EFFECTS Male Microbial Sensitivity Tests Mutation Proviruses/*DRUG EFFECTS/*GENETICS/PHYSIOLOGY Virus Replication/DRUG EFFECTS Zidovudine/*PHARMACOLOGY JOURNAL ARTICLE
931230
M93C0103

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