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Baseline zidovudine (ZDV) susceptibility, codon 215 mutation, viral load and syncytium-inducting characteristics(SI) of HIV isolates from ACTG protocol 194.




 

Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:137.

AIDS Clinical Trials Group protocol 194 is a placebo- controlled, randomized study to evaluate the short-term virologic effect of continuing ZDV, switching to ddI, or adding ddI in ZDV-resistant HIV-1 seropositive subjects with CD4 counts 100-300/microliter following greater than 1 yr prior ZDV therapy. The trial has accrued 81 subjects thus far; median pre-study duration of ZDV use was 2.6 yrs (25- 75% range 1.9-3.6 yrs). Median absolute baseline CD4 count was 187/microliter (136-241/microliter). To date, of 31 persons evaluated, 34% had a sensitive baseline ZDV phenotype (IC50 less than or equal to 0.1 micromolar) by the ACTG/DOD consensus assay, 34% were intermediate (0.1-1.0 micromolar), and 32% showed resistance (greater than or equal to 1.0 micromolar). For a subset (n= 23) of these patients, the occurrence of a mutation at pol codon 215 was associated with ZDV IC50 greater than or equal to 1.0 micromolar; genotypes were 35% wildtype, 30% mutant 215 codon, and 35% mixed. SI occurred in 11/20 of assayed baseline isolates, but did not appear more often with resistant isolates. IC50 showed no significant correlation with baseline viral load by quantitative HIV-RNA (n=23, bDNA assay) or p24 antigen (n=31). This ongoing trial shows high- level resistance at study entry for one-third of subjects who had received over 2 years of prior ZDV. ZDV susceptibility may not correlate with HIV-RNA, p24 antigen, or SI phenotype.

Drug Resistance, Microbial/*GENETICS HIV-1/*DRUG EFFECTS/ENZYMOLOGY/GENETICS Mutagenesis, Site-Directed Mutation RNA-Directed DNA Polymerase/GENETICS Zidovudine/*PHARMACOLOGY ABSTRACT



 




Information in this article was accurate in December 30, 1995. 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.