Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations.
PMID: 14551187
2004
The Journal of biological chemistry
Abstract: Additionally, we report how the decreased viral replication capacity of resistant viruses is directly linked to their decreased ability to use natural nucleotide substrates and that combination of the K65R and M184V resistance mutations leads to greater decreases in viral replication capacity.
Abstract: We report the molecular mechanisms by which a virus resistant to lamivudine with the M184V reverse transcriptase mutation shows increased susceptibility to tenofovir and can suppress the effects of the tenofovir resistance mutation K65R.
Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients.
PMID: 14976601
2004
The Journal of infectious diseases
Abstract: Response to tenofovir DF was reduced among patients with HIV-1 with >or=3 TAMs inclusive of either the M41L or L210W mutation (n=86) or patients who had a preexisting K65R mutation (n=6).
High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy.
PMID: 15044478
2004
The Journal of biological chemistry
Abstract: Consistent with this result, purified HIV-1 RT carrying K65R RT or K65R/L74V substitutions exhibits an 8-fold resistance to ddATP as judged by pre-steady state kinetics of incorporation of a single nucleotide into DNA.
Abstract: Here we show that recombinant viruses carrying K65R and K65R/L74V display the same resistance level to ddI (about 9.5-fold) relative to wild type.
Abstract: However, the K65R/L74V virus replication capacity is severely impaired relative to that of wild-type virus.
Abstract: Human immunodeficiency virus, type 1 reverse transcriptase (HIV-1
Human immunodeficiency virus type 1 reverse transcriptase mutation selection during in vitro exposure to tenofovir alone or combined with abacavir or lamivudine.
PMID: 15047556
2004
Antimicrobial agents and chemotherapy
Abstract: In the wild-type virus, TFV-ABC and TFV-3TC selected K65R (with reduced susceptibility to all three inhibitors) and then Y115F.
Abstract: Although several nucleoside reverse transcriptase inhibitors select RT mutations K65R and L74V, the combination of 65R + 74V is rare in clinics.
Abstract: Replication kinetic assays revealed that the mutant K65R + L74V is unstable, and 65R-->K reversion occurs during replication of virus in phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear (PBM) cells in the absence of selection pressure.
Abstract: To analyze the impact of these RT mutations on viral replication, a double mutant containing K65R + L74V was created by site-directed mutagenesis in a pNL4-3 background.
Abstract: Among treatment-naive patients who developed the K65R mutation in clinical trials, successful second line regimens were established.
Abstract: Based on clinical cut-offs established for the individual NRTIs, the phenotypic results with K65R suggest full-to-partial drug activity for multiple NRTIs, including tenofovir, against the K65R mutant.
Abstract: From cross-sectional genotypic analyses, the K65R mutation and TAMs appear to represent separate patterns of NRTI resistance.
Abstract: From in vitro phenotypic analysis, the K65R mutation shows no cross-resistance to zidovudine, but low-level resistance to tenofovir and the other NRTIs.
Primer unblocking by HIV-1 reverse transcriptase and resistance to nucleoside RT inhibitors (NRTIs).
PMID: 15183338
2004
The international journal of biochemistry & cell biology
Abstract: In addition, point mutations conferring resistance to NNRTIs (Y181C and L100I) or NRTIs (K65R, L74V, and M184V) partially resensitize the resistant viruses to AZT by inhibiting ATP-phosphorolysis.
Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial.
Abstract: Through 144 weeks, the K65R mutation emerged in 8 and 2 patients in the tenofovir DF and stavudine groups, respectively (P =.06).
Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients.
Abstract: High rates of early virologic failure associated with the emergence of the K65R mutation in HIV-1 reverse transcriptase (RT) have been reported among HIV-infected patients who received novel, tenofovir-containing, triple-nucleoside/nucleotide reverse transcriptase inhibitor (NRTI/NtRTI) regimens as their initial therapy.
Abstract: This review surveys the findings of prospective and retrospective studies in this regard, examines the significance of the K65R mutation and other factors associated with reports of early virologic failure among patients receiving tenofovir-containing NRTI/NtRTI regimens, and discusses clinical approaches to preventing and managing HIV drug resistance and treatme
HIV mutation literature information.
PMID: 
2004
The Journal of biological chemistry
Browser Board
Co-occurred Entities
Filtrator
ViMRT