WESTPORT, Apr 14 (Reuters Health) - Mutations induced in HIV-1 associated with incomplete suppression using zidovudine, didanosine and nevirapine show interpatient and temporal variability, according to the results of a randomized, double blind, placebo-controlled study.

Dr Richard T D'Aquila, of Massachusetts General Hospital, Charlestown, and a multicenter team following the AIDS Clinical Trials Group protocol 241, collected data on 57 HIV-1-positive patients. The 48-week study compared "combined zidovudine and didanosine to combined zidovudine, didanosine and nevirapine in subjects with HIV-1 infection and baseline CD4+ T-cell counts 350 cells per cubic millimeter or less."

Their report is published in the March issue of The Journal of Infectious Diseases. The investigators found that the nevirapine-selected mutations were reverse transcriptase (RT) 181C, 1190A and 101E. In addition, RT 130N and 188L were seen in a minority of viruses. Further, didanosine-resistance mutations were rare and there were 2 distinct zidovudine-resistance patterns.

According to the researchers, "the 2 different zidovudine-resistance mutations at codon 215 (215Y versus 215F) were associated with distinct patterns of mutations in other codons."

In longitudinal studies, the researchers found the pattern of resistance mutations changed. They suggest that this may be due to the selection of other mutations by the addition of other drugs, or to a process in which the original escape variant further mutates due to improved replicative capacity.

Dr D'Aquila and colleagues suggest that the important interactions that occur between resistance mutations "may affect drug susceptibility or replicative capacity and may influence the specific evolutionary routes to multidrug resistance."
http://www.ama-assn.org:80/special/hiv/newsline/reuters/04147976.htm