Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study.
PMID: 26831472
2016
The Lancet. Infectious diseases
Abstract: Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene.
Introduction: In individuals receiving tenofovir, HIV-1 develops phenotypically and clinically significant resistance usually as a result of one mutation at position 65 (lysine to arginine; K65R) in the reverse transcriptase (RT) gene.
Method: Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the RT gene.
Discussion: Despite evidence for diminished replication of tenofov
Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors.
Abstract: A derivative was created, additionally harboring the TAM K70R and the reversions M151Q as well as R65K since K65R antagonizes excision.
Abstract: In addition, K65R, known to antagonize AZTMP excision in HIV-1 subtype B was present.
Result: A62V and S68G restore the impaired nucleotide incorporation of the K65R mutation, thus improving the replication capacity of the virus.
Result: A second variant was constructed which in addition harbors the reversal R65K (MR-65K-70R), to abrogate negative effects of K65R on AZT excision.
Result: Although analyses with subtype B RT indicated tha
High fidelity simian immunodeficiency virus reverse transcriptase mutants have impaired replication in vitro and in vivo.
Abstract: Direct virus competition assays demonstrated a rank order of wild-type>K65R>V148I mutants in terms of viral fitness.
Abstract: In single round in vitro-replication assays, SIVmac239-K65R demonstrated significantly higher fidelity than wild-type, and rapidly reverted to wild-type following infection of macaques.
Abstract: SIVmac239-K65R and SIVmac239-V148I viruses had reduced replication capacity compared to wild-type SIVmac239.
Abstract: Thus, we showed that RT mutants, and specifically the common K65R drug-resistance mutation, had impaired replication capacity and higher fidelity.
Abstract: We investigated the effect of RT mutations K65R,
Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.
PMID: 26953333
2016
The Journal of antimicrobial chemotherapy
Abstract: K65R emerged in hal
Abstract: BACKGROUND: K65R is a relatively rare drug resistance mutation (DRM) selected by the NRTIs tenofovir, didanosine, abacavir and stavudine and confers cross-resistance to all NRTIs except zidovudine.
Abstract: CONCLUSIONS: A high rate of K65R emergence may suggest that ingesting low doses of lamivudine via breast milk could select for this mutation.
Abstract: Factors associated with K65R emergence were assessed using Fisher's exact test and the Wilcoxon rank-sum test.
Abstract: Infants with K65R had low baseline CD4 cell counts (P = 0.014), were more likely to have DRMs earlier (<=6 weeks versus >=14 weeks, P = 0.007) and were more likely to have multiclass drug resistance (P = 0.035).
Sensitive sentinel mutation screening reveals differential underestimation of transmitted HIV drug resistance among demographic groups.
Abstract: One-third of K65R was in persons who also had at least one of the other mutations screened.
Abstract: Sensitive screening identified 72% more TDR than conventional sequencing for the five mutations assessed (13.6 vs. 7.9%, P < 0.0001), with K65R having the greatest increase (0-1.7%).
Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa.
PMID: 27002368
2016
AIDS research and human retroviruses
Result: Of those with NRTI mutations, five (0.7%) had only the M184V mutation, two (0.3%) had the K65R mutation alone, one (0.1%) had the M41L mutation alone, and two (0.3%) had multiple thymidine analogue mutations (one with M184V).
Discussion: From the 2012 samples, there were two cases of transmission of the K65R mutation, which is selected for by tenofovir (TDF) and which had been introduced into first-line regimens in South Africa 2 years earlier in 2010.
Discussion: Generally, the prevalence of transmitted K65R mutants has been low in settings with widespread exposure to tenofovir-containing ART regimens.
Discussion: It had been previously shown that K65R emerges more frequently in subtype C
Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya.
Abstract: Antiretroviral-naive adults initiating antiretroviral therapy in Nairobi, Kenya were tested for HIV-1 drug resistance at codons K103N, Y181C, G190A, M184V, and K65R using an oligonucleotide ligation assay.
Abstract: Resistance to tenofovir (K65R) was found in 2014 but not in 2006.
Introduction: Introduction: Fifty-eight had mutations to NNRTI, two had only lamivudine mutations, and two had only tenofovir (K65R) mutations.
Introduction: Finally, although OLA for K65 was not performed among all 386 participants in 2006, pyrosequencing performed on the 54 participants with subsequent virologic failure found no K65R in this cohort.
Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System.
Abstract: In terms of loci, the detection rate of the alleles was greater than 97% for M41L,
Introduction: In this study, we established a multiplex assay for detecting the drug resistance mutations at 8 loci (M41L, K65R, K101E/Q/P, K103N/S, M184V, G190A, L210W and T215F/Y), which are associated with resistance to commonly used nucleoside reverse transcriptase inhibitors (NRTIs) and Non-nucleoside reverse transcriptase inhibitors (NNRTIs) based on the automated MassARRAY system (Sequenom).
Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses.
Result: However, this trend did not reach statistical significance for the K65R versus H51Y/R263K-K65R viruses (P = 0.08).
Result: In viruses carrying K65R, E138K, or M184V, the additional presence of R263K in IN coding sequence caused a further impact on viral replication than was associated with any of these RT mutations on their own.
Result: Our results show that the addition of R263K to the K65R-, L74V-, K103N-, E138K-, or M
High resistance barrier to tenofovir alafenamide is driven by higher loading of tenofovir diphosphate into target cells compared to tenofovir disoproxil fumarate.
Abstract: Using a newly developed virus breakthrough assay with TAF exposure set at physiological concentrations, we show that HIV-1 clinical isolates harboring TFV resistance mutations such as K65R, 3 or 4 thymidine-analog mutations (TAMs), Q151M/K65R, or T69 insertion complex could be inhibited by TAF, but not by TFV when used at clinically relevant concentrations for TDF.
HIV mutation literature information.
PMID: 
2016
The Lancet. Infectious diseases
Browser Board
Co-occurred Entities
Filtrator
ViMRT