Evaluating the role of etravirine in the second-line antiretroviral therapy after failing an initial non-nucleoside reverse transcriptase inhibitor-based regimen in a resource-limited setting.
Abstract: Patients with K65R (3.4% vs 17.9%, p=0.005), Q151M (5.9% vs 20.5%, p=0.012), and multi-NRTI resistance mutations (16.8% vs 48.7%, p<0.001) when compared to patients with >2 etravirine-RAMs.
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.
Method: D67N/K70R/ 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: By comparison, K65R RT demonstrated 12.4-, 12.0-, and 13.1-fold-higher levels of resistance, respectively, toward the same analogs.
National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation.
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: 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 K70E mutations also profoundly impaired the ability of RT to excise 3'-azido-2',3'-dideoxythymidine monophosphate (AZT-MP) and other NRTI
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.
HIV mutation literature information.
PMID: 
2008
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