Comparative anti-HIV evaluation of diverse HIV-1-specific reverse transcriptase inhibitor-resistant virus isolates demonstrates the existence of distinct phenotypic subgroups
| Autor: | Valerie Fliakas-Boltz, Michael R. Boyd, Michael J. Currens, Tracy L. Stup, Joseph L. Roberson, William Decker, C A Pyle, E L White, James B. McMahon, Robert W. Buckheit |
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| Rok vydání: | 1995 |
| Předmět: |
Calanolide A
Biology Antiviral Agents Virus Cell Line Zidovudine Virology medicine Humans Drug Interactions Pharmacology chemistry.chemical_classification Reverse-transcriptase inhibitor Nucleoside analogue Reproducibility of Results virus diseases Drug Resistance Microbial Nucleotidyltransferase HIV Reverse Transcriptase Reverse transcriptase Phenotype Enzyme chemistry HIV-1 Drug Evaluation Reverse Transcriptase Inhibitors medicine.drug |
| Zdroj: | Antiviral Research. 26:117-132 |
| ISSN: | 0166-3542 |
| Popis: | We have biologically and biochemically evaluated a structurally diverse group of HIV-1-specific reverse transcriptase (RT) inhibitors and determined that the members of this class share many common properties. These include reproducible and selective antiviral activity against a panel of biologically distinct laboratory and clinical strains of HIV-1, activity against HIV-1 in a wide variety of cultured and fresh human cells, and potent inhibition of HIV-1 RT when evaluated using a heteropolymeric ribosomal RNA template assay. Each of the HIV-1-specific compounds was capable of inhibiting HIV replication when challenged at high m.o.i., further distinguishing them from the nucleoside analogs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). When tested in combination with AZT, each of the HIV-1-specific compounds synergistically inhibited the replication of HIV-1. HIV-1 isolates resistant to different HIV-1-specific inhibitors exhibited heterogeneous patterns of cross-resistance to other members of this pharmacologic class. Four distinct phenotypic classes have been defined through the use of drug-resistant virus isolates which derive from distinct mutations in the RT. These results indicate that the various subgroups of HIV-1-specific inhibitors interact differently with HIV-1 RT, suggesting important potential implications for drug combination therapeutic strategies. |
| Databáze: | OpenAIRE |
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