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