Increased ability for selection of zidovudine resistance in a distinct class of wild-type HIV-1 from drug-naive persons
| Autor: | H Weinstock, K Blumoff, Walid Heneine, J G Garcia-Lerma, S Nidtha |
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| Rok vydání: | 2001 |
| Předmět: |
Anti-HIV Agents
Molecular Sequence Data HIV Infections Drug resistance Biology Virus Replication Evolution Molecular Zalcitabine Zidovudine Drug Resistance Viral medicine Humans Didanosine Recombination Genetic Genetics Multidisciplinary Base Sequence Stavudine Wild type virus diseases Virology Dideoxynucleosides HIV Reverse Transcriptase Reverse transcriptase Viral replication Mutagenesis DNA Viral HIV-1 Commentary Reverse Transcriptase Inhibitors medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 98:13907-13912 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Transmission of HIV-1 with reduced susceptibility to antiretroviral drugs raises public health concerns. Through surveillance of drug-resistant HIV-1 in 603 treatment-naïve, recently diagnosed HIV-1-infected persons, we identified a distinct group of viruses that have mutations at codon 215 of the reverse transcriptase (RT) gene that are different from either the wild-type (WT) T or the zidovudine (AZT)-selected T215Y/F. These mutations included 215D/C/S and were found in 20 patients (3.3%). The 215D, 215C, and 215S mutations differ from 215Y by a 1-nt change compared with 2 nt for the WT T215 and likely represent revertants of 215Y. These viruses all were found to have WT susceptibility to AZT, and all replicated efficiently as WT HIV-1 T215 . However, differences in fitness among HIV-1 215D , HIV-1 215C , and HIV-1 215S were seen when RT backgrounds were changed, demonstrating a role of the RT background in the selection of these revertants. In vitro selection with AZT showed that HIV-1 215D and HIV-1 215C acquired 215Y more rapidly than did WT HIV-1 T215 , likely reflecting the need for only 1-nt change to evolve to 215Y. Our study demonstrates that HIV-1 with unusual mutations at codon 215 replicate efficiently, have WT susceptibility, and are commonly found in treatment-naïve persons. The increased ability for selecting resistance mutations defines this class of WT HIV-1 and highlights the higher potential of these viruses to compromise the efficacy of antiretroviral therapy. |
| Databáze: | OpenAIRE |
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