lamivudine-triphosphate has been researched along with abacavir* in 2 studies
2 other study(ies) available for lamivudine-triphosphate and abacavir
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Novel drug resistance pattern associated with the mutations K70G and M184V in human immunodeficiency virus type 1 reverse transcriptase.
We describe an unusual pathway of human immunodeficiency virus type 1 reverse transcriptase resistance during therapy with tenofovir-emtricitabine, characterized initially by the mutations K70E and M184V and later by K70G and M184V, with the two mutations coexisting on the same viral genome. Phenotypic resistance to lamivudine, emtricitabine, abacavir, didanosine, and tenofovir was observed, whereas susceptibility to zidovudine and stavudine was preserved. Topics: Adenine; Amino Acid Substitution; Deoxycytidine; Didanosine; Dideoxynucleosides; Drug Resistance, Multiple, Viral; Emtricitabine; HIV Reverse Transcriptase; HIV-1; Humans; Lamivudine; Molecular Sequence Data; Mutation; Organophosphonates; Reverse Transcriptase Inhibitors; Stavudine; Tenofovir; Zidovudine | 2007 |
Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors.
The K70E mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) has become more prevalent in clinical samples, particularly in isolates derived from patients for whom triple-nucleoside regimens that include tenofovir (TNV), abacavir, and lamivudine (3TC) failed. To elucidate the molecular mechanism by which this mutation confers resistance to these nucleoside RT inhibitors (NRTI), we conducted detailed biochemical analyses comparing wild-type (WT), K70E, and K65R HIV-1 RT. Pre-steady-state kinetic experiments demonstrate that the K70E mutation in HIV-1 RT allows the enzyme to discriminate between the natural deoxynucleoside triphosphate substrate and the NRTI triphosphate (NRTI-TP). Compared to the WT enzyme, K70E RT showed 2.1-, 2.3-, and 3.5-fold-higher levels of resistance toward TNV-diphosphate, carbovir-TP, and 3TC-TP, respectively. By comparison, K65R RT demonstrated 12.4-, 12.0-, and 13.1-fold-higher levels of resistance, respectively, toward the same analogs. NRTI-TP discrimination by the K70E (and K65R) mutation was primarily due to decreased rates of NRTI-TP incorporation and not to changes in analog binding affinity. The K65R and K70E mutations also profoundly impaired the ability of RT to excise 3'-azido-2',3'-dideoxythymidine monophosphate (AZT-MP) and other NRTI-MP from the 3' end of a chain-terminated primer. When introduced into an enzyme with the thymidine analog mutations (TAMs) M41L, L210W, and T215Y, the K70E mutation inhibited ATP-mediated excision of AZT-MP. Taken together, these findings indicate that the K70E mutation, like the K65R mutation, reduces susceptibility to NRTI by selectively decreasing NRTI-TP incorporation and is antagonistic to TAM-mediated nucleotide excision. Topics: Adenine; Amino Acid Substitution; Anti-HIV Agents; Cytidine Triphosphate; Dideoxynucleosides; Dideoxynucleotides; Drug Resistance, Multiple, Viral; Genotype; Glutamic Acid; HIV Reverse Transcriptase; HIV-1; Humans; Lamivudine; Lysine; Mutagenesis, Site-Directed; Organophosphonates; Phenotype; Reverse Transcriptase Inhibitors; Tenofovir; Thymine Nucleotides; Zidovudine | 2007 |