Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda.
PMID: 24633208
2014
The Journal of antimicrobial chemotherapy
Abstract: In multivariate regression models, K65R, Y115F and the presence of thymidine analogue-associated mutations were associated with increased susceptibility to etravirine in the cABC arm.
Result: However, in the case of etravirine, K65R, Y115F
Discussion: Although our results are based on a small number of observations (K65R was only observed in one individual) and interpreted cautiously, the associations with TAMs and K65R have been reported previously, but this is, to our knowledge, the first report of an effect of Y115F.
Discussion: However, we did find that the presence of TAMs, K65R and Y115F were independent predictors of increased etravirine susceptibility.
Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia.
Result: A K65R mutation was also detected in a slow responding patient.
Result: Combined NNRTI and NRTI mutations were seen in four of nine (44.4%) participants and involved M184V/I in all cases and K65R and D67G occurred in one participant in addition to the M184I mutation.
Discussion: However, one of the virological failure also carried K65R; and the difference in virological outcome of these patients could be due to modulation of fitness cost by mutational interactions.
Discussion: This may be due to the K65R mutation that can impair replicative fitness of the virus.
HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial.
PMID: 24740633
2014
The Journal of infectious diseases
Result: Among those randomized to placebo, 1 participant had 0.69% K65R by qMVA and 1.64% by deep sequencing.
Result: Of the seroconverters randomized to FTC/TDF, none showed minor variant mutations above the BCO at
Discussion: Among PrEP users with preexisting infection in other trials, K65R appeared after 4 weeks of TDF PrEP in 1 person, and after 7 months of FTC/TDF PrEP in another.
Discussion: In GS-934, a randomized study of FTC/TDF/efavirenz (EFV) versus 3TC/TDF/EFV in infected ART-naive subjects, 2/19 developed M184V or I while none developed K65R or K70E after treatment for a median of 16 weeks postvirologic failure.
Discussion: The absence K65R or K70E in iPrEx may be due to insufficient duration of TDF exposure.
High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen.
Abstract: The frequency of reduced susceptibility to didanosine was substantial in the abacavir-exposed group (69.1%).This reduced susceptibility was commonly attributed to L74V/I (n = 44) and to a lesser extent K65R (n = 10) mutations.
Abstract: The presence of the K65R mutation was more common after abacavir pressure (12.3% vs 1.8%).
Result: K65R was more common among children failing ABC-based regimens (n = 10, 12.3%) compared to the d4T-exposed group (n = 5, 1.8%, p = 0.0003).
Discussion: Both the presence of TAMs and K65R has an impact on the NRTI options available for 2nd and 3rd-line regimens.
Discussion: Due to the relatively low prevalence of both TAMs and K65R, the majority of children remain susceptible to AZT
Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors.
PMID: 24867966
2014
Antimicrobial agents and chemotherapy
Abstract: Biochemical assays demonstrated that W153L alone or in combination with K65R, M184I, K101E, K103N, E138K, and Y181C impaired enzyme processivity and polymerization efficiency but did not diminish RNase H activity, providing mechanistic insights into the low replicative fitness associated with these substitutions.
Abstract: To investigate the impact of W153L, alone or in combination with the clinically relevant RT resistance substitutions K65R (change of Lys to Arg at position 65), M184I, K101E, K103N<
HIV reverse-transcriptase drug resistance mutations during early infection reveal greater transmission diversity than in envelope sequences.
PMID: 24924164
2014
The Journal of infectious diseases
Abstract: Clonal sequencing verified low-level K65R at frequencies of 0.4%-4.9%.
Abstract: In each case, K65R coexisted unlinked with variants carrying 2-5 thymidine analog mutations at frequencies of 1.6%-23.0%.
Abstract: The samples were screened with sensitive polymerase chain reaction assays for the commonly transmitted M41L and K70R mutations and for K65R, which was undetected by bulk sequencing.
HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania.
Discussion: K65R is selected frequently (4%-11%) in patients with some nonsubtype-B clades for whom stavudine-containing regimens are failing in the absence of tenofovir.
Discussion: As with tenofovir, the K65R mutation may be selected by didanosine, abacavir, or stavudine (particularly in patients with nonsubtype-B clades) and is associated with decreased viral susceptibility to these drugs.
Discussion: Data are lacking on the potential negative impact of K65R on clinical response to didanosine.
Discussion: The presence of K65R is associated with a reduced virologic response to tenofovir.13 A reduced response also occurs in the presence of 3 or more TAMs inclusive of either M41L or L210W.
Discussion: The presence of TAMs or combined treatment with zidovudine pr
Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase.
Abstract: However, direct associations of K70S with mutations within the Q151M-complex and of K70T with K65R were observed.
HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia.
PMID: 25141905
2014
Journal of the International AIDS Society
Method: Sensitivity analysis was performed by including K65R in our definition of multi-NRTI RAMs as this mutation is associated with reduc
Result: As the results of this sensitivity analysis are similar to those presented in Table 2, the absence of K65R in our multi-NRTI RAM definition did not significantly alter the analysis outcome.
Result: When K65R was included in the sensitivity analysis, a total of 46/105 (44%) patients were classified as harbouring multi-NRTI RAMs.
Discussion: This prevalence was higher than the 12.7% reported from a Cambodian study, although it is important to note that multi-NRTI RAMs in that study included Q151M, K65R and 69Ins.
HIV mutation literature information.
PMID: 
2014
The Journal of antimicrobial chemotherapy
Browser Board
Co-occurred Entities
Filtrator
ViMRT