Important note: Information in this article was accurate in October 2002. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; October 14, 2002
Michael Greer, Senior Medical Writer
"Recent studies have shown that the accumulation of multiple mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance may be grouped as multi-NRTI resistance (MNR) complexes," according to Miguel E. Quinones-Mateu and colleagues at the Cleveland Clinic Foundation in the United States and the Germans Trias i Pujol University Hospital in Badalona and the Free University of Madrid in Spain.
While single resistance mutations generally reduce overall fitness, this effect can be ameliorated in MNR-carrying viral strains, Quinones-Mateu and coauthors found.
The researchers examined HIV variants engineered to carry reverse transcriptase from clinical isolates with the MNR 69 insertion complex. These clinical strains carried a serine insertion between residues 69 and 70 that was removed in some forms of the recombinant virus, they said.
Not surprisingly, MNR 69 viruses demonstrated improved fitness compared with wild-type strains in the presence of the NRTI zidovudine. However, in a drug-free environment, viral strains carrying the T69S mutation with the rest of the MNR 69 complex also proved to be more fit than wild-type viruses with the serine insertion alone, study data showed.
Moreover, this mutation also conferred enhanced fitness to MNR 69 viruses over strains with all of the MNR 69 complex except for the T69S insertion (Insertions in the reverse transcriptase increase both drug resistance and viral fitness in a human immunodeficiency virus type 1 isolate harboring the multinucleoside reverse transcriptase inhibitor resistance 69 insertion complex mutation. J Virol 2002 Oct;76(20):10546-52).
"These results suggest that RT insertions, in the right sequence context (i.e., additional mutations contained in the MNR 69 insertion complex), enhance NRTI resistance and may improve viral fitness," Quinones-Mateu and colleagues concluded. "Thus, comparing complex mutation patterns with viral fitness may help to elucidate the role of uncharacterized drug resistance mutations in antiretroviral treatment failure."
The corresponding author for this report is Miguel E. Quinones-Mateu, Cleveland Clinic Foundation, Lerner Research Institute, Department of Virology/NN10, 9500 Euclid Avenue, Cleveland, OH 44195 USA. E-mail: quinonm@ccf.org.
Key points reported in this study include:
This article was prepared by AIDS Weekly editors from staff and other reports.
Reference
Quinones-Mateu ME, Tadele M, Parera M, et al., "Insertions in the reverse transcriptase increase both drug resistance and viral fitness in a human immunodeficiency virus type 1 isolate harboring the multi-nucleoside reverse transcriptase inhibitor resistance 69 insertion complex mutation", J Virol 2002 Oct;76(20):10546-52
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