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Evolution of zidovudine resistant HIV-1 isolates assessed by clonal analysis.


Int Conf AIDS. 1992 Jul 19-24;8(1):Th79 (abstract no. ThA 1571). Unique

OBJECTIVES: To determine the evolution of 5 zidovudine conferring mutations on the HIV-1 reverse transcriptase (RT) gene during therapy. METHODS: Sequential HIV-1 isolates obtained from 2 initially asymptomatic individuals who progressed to AIDS during zidovudine therapy, were analyzed. The viral genome encoding for RT was amplified by PCR and cloned. Multiple clones from each isolate were sequenced. RESULTS: The first mutation appears at codon 70. After half a year of treatment 4 different populations are present; 215 alone, 215 + 70 or 215 + 41, and 41 alone. Thereafter outgrowth of 1 population with 2 mutations, 41 + 215, occurs in 1 patient. In the other patient, beside a 41 + 215 mutant population, another population with 4 mutations (41 + 67 + 70 + 215) is present after 1 year. Another year later, only a population with all 5 mutations (41 + 67 + 70 + 215 + 219) is present. CONCLUSIONS: During treatment of asymptomatic individuals, a specific pattern of zidovudine conferring mutations develops over time. Selection of the most resistant population from a pool of different populations seems to contribute to the evolution of resistant viruses.

Cloning, Molecular Drug Resistance, Microbial/GENETICS DNA Mutational Analysis Evolution Genes, Viral Human HIV Infections/DRUG THERAPY/MICROBIOLOGY HIV-1/*DRUG EFFECTS/GENETICS/ISOLATION & PURIF RNA-Directed DNA Polymerase/ANTAGONISTS & INHIB/DRUG EFFECTS/ GENETICS Zidovudine/*PHARMACOLOGY ABSTRACT


Information in this article was accurate in December 30, 1992. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.