HIV type 1 subtype C drug resistance among pediatric and adult South African patients failing antiretroviral therapy.
PMID: 19000027
2008
AIDS research and human retroviruses
Abstract: Ninety-one percent of patients harbored resistance mutations; the most frequent NRTI mutations were M184V/I (37%), D67N (32%), T215Y/F (25%), K70R (21%), M41L (20%), K219Q/E (14%), and K65R (14%), reflecting the frequent use of lamuvidine and zidovudine.
Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency.
Introduction: The K65R, K70E, L74V, Q151M and M184V mutations primarily increase the selectivity of RT for the incorporation of a natural dNTP substrate over a NRTI-triphosphate.
Result: Accordingly, we were also interested in the ability of RT enzymes conta
Discussion: Another unique feature of subtype C virus is that the K65R mutation which develops in subtype C is AGG, whereas in subtype B it is almost exclusively AGA (data not shown).
Discussion: There have been recent suggestions that silent mutations in the subtype C RT gene were responsible for the rapid selection of the K65R mutation.
Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance.
Result: The mutations K65R, K70E, L74V, Q151 M, and M184V increase the selectivity of RT for incorporation of the natural dNTP substrate versus the NRTI-triphosphate (NRTI-TP).
Role of genetic diversity amongst HIV-1 non-B subtypes in drug resistance: a systematic review of virologic and biochemical evidence.
Abstract: Mechanistic research explored resistance to the integrase inhibitor raltegravir, K65R-mediated resistance to tenofovir and the role of connection domain mutations in resistance to zidovudine.
Site-directed mutagenesis in the fingers subdomain of HIV-1 reverse transcriptase reveals a specific role for the beta3-beta4 hairpin loop in dNTP selection.
Abstract: The K65A mutant behaved similarly to the deletion mutant displaying dependence on Watson-Crick hydrogen bonding, increased fidelity and reduced dNTP-binding, while the K65R was more akin to wild-type enzyme.
Abstract: Two substitution mutants, K65R and K65A were studied.
Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors.
PMID: 17088490
2007
Antimicrobial agents and chemotherapy
Abstract: 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.
Abstract: By comparison, K65R RT demonstrated 12.4-, 12.0-, and 13.1-fold-higher levels of resistance, respectively, toward the same analogs.
Abstract: 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.
Abstract: The K65R and
Options for a second-line antiretroviral regimen for HIV type 1-infected patients whose initial regimen of a fixed-dose combination of stavudine, lamivudine, and nevirapine fails.
Abstract: Patients with an HIV-1 RNA load of >4 log copies/mL at the time of treatment failure had higher prevalence of thymidine analogue mutations (P=.041), K65R (P=.031), and Q151M (P=.008) mutations.
Abstract: Thymidine analogue mutations, K65R, and Q151M were observed in 37%, 6%, and 8% of patients, respectively.
Human immunodeficiency virus type 1: resistance to nucleoside analogues and replicative capacity in primary human macrophages.
Abstract: In contrast, mutant viruses exhibited strongly impaired RC relative to the wild type (WT) in macrophages, with the following RC order: WT > two TAMs > four TAMs = M184V > K65R.
Abstract: Mutant viruses bearing thymidine analogue mutations (TAMs) or the K65R mutation had similar resistance levels in the two cell types.
Biochemical studies on the mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to 1-(beta-D-dioxolane)thymine triphosphate.
PMID: 17403997
2007
Antimicrobial agents and chemotherapy
Abstract: A lower degree of resistance to DOT-TP than to tenofovir diphosphate or carbovir-TP was found for RT containing the K65R mutation.
Abstract: The results suggest that DOT, compared with other approved nucleoside analogs, is overall more resilient to mutations such as TAM, M184V, and K65R, which are commonly found in viruses derived from subjects failing multinucleoside therapy.
HIV mutation literature information.
PMID: 
2008
AIDS research and human retroviruses
Browser Board
Co-occurred Entities
Filtrator
ViMRT