Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis.
PMID: 23305651
2012
Journal of the International AIDS Society
Introduction: K65R
Introduction: A lysine to arginine mutation at position 65 of the RT (K65R), which confers a two- to four-fold decrease in susceptibility to tenofovir, is included on all drug resistance lists and has historically been considered the classic tenofovir-associated mutation.
Method: Tenofovir-associated resistance mutations included K65R, T69 insertion, K70E and >=3 thymidine-analogue mutations (TAMs; M41L, D67N, K70R, L210W, T215F/Y, K219Q/E), inclusive of either M41L or L210W.
Genotypic impact of prolonged detectable HIV type 1 RNA viral load after HAART failure in a CRF01_AE-infected cohort.
PMID: 20854169
2011
AIDS research and human retroviruses
Abstract: NNRTI mutations, M184I/V mutation, thymidine analogue mutations, and K65R were observed in 78.9%, 69%, 20%, and 12.7% of patients, respectively.
Tenofovir (TDF)-selected or abacavir (ABC)-selected low-frequency HIV type 1 subpopulations during failure with persistent viremia as detected by ultradeep pyrosequencing.
PMID: 20929395
2011
AIDS research and human retroviruses
Abstract: Among the eight tenofovir-treated subjects, three showed high-frequency (>20%) RT K65R at the time of failure, whereas one showed low-frequency (<20%) L74V; no low-frequency K65R was detected in these subjects.
Abstract: Among the nine abacavir-treated subjects, three showed low-frequency K65R; no L74V was detected in these patients.
Abstract: No K65R or L74V was detected in the samples from the control subject.
Abstract: UDPS of the HIV-1 reverse transcriptase (RT) (amino acids 56-120) was performed to detect the key mutations K65R and L74V associ
Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naive patients.
Abstract: K65R, K103N, and M184V variants at low frequencies were detected by allele-specific real-time PCR.
Abstract: Four patients with the M184V mutation also harbored the K65R or the K103N mutation.
Abstract: RESULTS: Minority drug-resistant HIV-1 variants were detected in 20/146 patients (13.7%): the M184V mutation in 12/146 patients (8.2%), the K103N mutation in 8/146 patients (5.5%), and the K65R mutation in 4/146 patients (2.7%).
Minority HIV mutation detection in dried blood spots indicates high specimen integrity and reveals hidden archived drug resistance.
Abstract: STUDY DESIGN: Evaluate nucleic acids from the DBS of 33 antiretroviral-experienced subtype B-infected subjects for minority M41L, K65R, K70R, K103N, Y181C, M184V, and T215Y/F mutations by real-time PCR.
"K70Q adds high-level tenofovir resistance to ""Q151M complex"" HIV reverse transcriptase through the enhanced discrimination mechanism."
Result: Notably, this isolate showed an increase in resistance to TFV-DF in the absence of the canonical TFV resistance mutation (K65R) and in the presence of Q151Mc mutations.
Discussion: However, we believe that similar to K65R, its prevalence will increase, as tenofovir use continues to rise.
Discussion: Moreover, K70Q/Q151Mc is at least twice as resistant to TFV as the well-known TFV-resistant K65R in the background of Q151Mc (as reported in the Stanford HIV Drug Resistance Database).
Discussion: Similarly, clinical isolates deposited at the Stanford HIV resistance database and carrying the Q151Mc mutation were also susceptible to TFV-DF, unless they also had the K65R mutation.
A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus.
Introduction: Additionally, virion-associated RT containing K65R+L74I mutations showed increased processivity in a single round of reverse transcription in comparison to K65R+L74V.
Introduction: Analysis of database (Monogram Biosciences, South San Francisco, CA) have shown that thymidine analogue mutations (TAMs) and M184V are the most common (>25%) followed by L74V/I (11%) and K65R (3.3%) mutations during clinical trials.
Introduction: Interesting observation regarding the absence of selection of K65R and L74V in the same virus by Bazmi et al.
Detection of low-level K65R variants in nucleoside reverse transcriptase inhibitor-naive chronic and acute HIV-1 subtype C infections.
PMID: 21257741
2011
The Journal of infectious diseases
Abstract: To substantiate reports of greater emergence of the K65R nucleoside reverse transcriptase inhibitor (NRTI) mutation in human immunodeficiency virus type 1 (HIV-1) subtype C, we examined natural low-level K65R expression in subtype C relative to subtypes B and AE.
Abstract: We found low-level K65R of unknown clinical significance in NRTI-naive subtype C-infected women and infants at frequencies above the natural occurrence in subtypes B and AE.
Multi-nucleoside reverse transcriptase inhibitor resistant HIV type-1 in a patient from Sierra Leone failing stavudine, lamivudine and nevirapine.
Abstract: We report a 33-year-old HIV type-1 (HIV-1)-infected male from Sierra Leone who harboured extensive drug resistance mutations to all nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs, including the multi-NRTI-resistance Q151M complex, K65R, M184I and Y181I, after using standard first-line generic fixed-dose stavudine, lamivudine and nevirapine (Triomune ) for 36 months.
The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?
HIV mutation literature information.
PMID: 
2012
Journal of the International AIDS Society
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