The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy.
Discussion: D4T use was associated with the emergence of K65R and K70E mutations in 30% of patients.
Discussion: For patients on ZDV, some mutations apparently selected by d4T (K65R, K70E) may have diminished to levels below the limit of detection, resulting in an underestimate in the prevalence of these mutations.
Discussion: The use of d4T in subtype C virus does not follow predictable patterns in the emergence of mutations and appears to be promiscuous in its ability to select for K65R and K70E (associated with TDF resistance), multiple TAM pathways, Q151M, and T69 insertions.
Analysis of the diversity of the HIV-1 pol gene and drug resistance associated changes among drug-naive patients in Burkina Faso.
Introduction: In addition, there is a strong negative association of K65R with the M184V, L74V and K70E mutations, conferring resistance to 3TC/FTC, ddI and TDF, respectively.
National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation.
Abstract: Absence of selection of K70E in 850 HIV-1-infected naive patients suggests its role in NRTI drug resistance.
Abstract: According to occurrence of K70E mutation after failure to TDF regimen, this mutation was recently reported as a mutation associated with TDF resistance in most resistance genotypic algorithms.
Abstract: At the time of K70E selection, 60% of patients had received or received TDF-containing regimen and one-third received exclusive NRTI regimen.
Abstract: Concomitant association of K65R and K70E was possible but infrequent (11%).
Abstract: Conversely with K65R mutation, thymidine analog mutations (TAMs) can be concomi
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.
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).
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: 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.
Abstract: 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).
Abstract: Taken together, these findings indicate that th
National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation.
Abstract: CONCLUSION: This is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo.
Method: The K70E test used the mutation-specific primer 70E.REV with the primer 70.FWD and probe 70.2P.
Result: Further sequencing of the plasma RNA revealed that this K70E virus had also G196R, but not S68N; although it did not have I178M, this K70E virus therefore resembled the virus that was detected early after the start of tenofovir treatment (see table 1, week 24 isolate).
Result: While population genotyping of DNA from PBMC-derived virus isolates detected K70E mutants in only 10 animals, the real-time PCR method detected
Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.
Conclusion: The current findings with RT-SHIV are consistent with but also extend previous observations on the K65R mutation in the SIV model, with the novel observation of the tenofovir-selected K70E mutation (which was not detected by population sequencing in tenofovir-treated SIVmac251-infected macaques).
Figure: At the onset of tenofovir therapy (i.e, baseline, BL), no K65R and K70E virus could be detected.
Figure: Despite an initial rebound associated with emergence of K70E followed by K65R viral mutants (table 1.
Figure: Kinetics of K70E and K65R RT mutants during tenofovir therapy.
Figure: Plasma viral RNA sampl
Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.
HIV mutation literature information.
PMID: 
2009
AIDS (London, England)
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