Introduction: In this study, we sought to determine the virologic outcomes and rate of K65R emergence amongst patients with virologic failure after initiating TDF-containing ART as first-line treatment in a clinic in Durban, South Africa.
Introduction: In vitro studies provide some evidence for more rapid selection of K65R in subtype C virus.
Introduction: Th
Introduction: The K65R mutation has been reported in 7-15% of patients failing d4T-, ddI- or zidovudine-(AZT) containing first or second-line ART in South Africa, where subtype C accounts for most HIV-1 infections, compared to 2-5% of patients in parts of the world where infection with subtype B dominates.
Method: Univariate and multivariate logistic regression were used to identify variables associated with the presence of K65R.
Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.
PMID: 22784038
2012
The New England journal of medicine
Abstract: K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment.
Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal.
Abstract: BACKGROUND: We reported previously that while prolonged tenofovir monotherapy of macaques infected with virulent simian immunodeficiency virus (SIV) resulted invariably in the emergence of viral mutants with reduced in vitro drug susceptibility and a K65R mutation in reverse transcriptase, some animals controlled virus replication for years.
Result: As described in detail previously and summarized in Table 1 and Figure 1, five animals were infected at birth or at juvenile age with either wild-type SIVmac251 (n = 3), a K65R isolate derived from SIVmac251 (n = 1) or RT-SHIV (a chimeric SIV containing HIV-1 RT).
Result: For animal 33091, plasma collected at the time of tenofovir withdrawal and at the time of euthanasia (41 weeks after tenofovir withdrawal) had pure K65R
Trends in HIV-1 reverse transcriptase resistance-associated mutations and antiretroviral prescription data from 2003-2010.
Abstract: RESULTS: In the unfiltered data set (n=107,231), the prevalence in 2010 decreased compared to 2003 for all nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) RAMs, such as M184V/I (44.0% to 17.9%), T215Y (22.7% to 4.1%), and K65R (4.3% to 2.1%).
Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy.
Abstract: RESULTS: The cross-sectional study carried out with > 200 HIV-1 genotypes showed that virological failure to tenofovir/emtricitabine was strongly associated with the presence of M184V (P < 10-10) and TAMs (P < 10-3), while K65R was relatively uncommon in previously-treated patients failing antiretroviral therapy.
Disc
Discussion: K65R exerts an antagonistic effect on TAMs, by decreasing the ATP-mediated phosphorolytic activity that facilitates removal of NRTIs.
Discussion: In agreement with those findings, our cross-sectional study involving previously treated patients reveals that the presence of TAMs and M184V contributes to failure of salvage therapies containing the combination of tenofovir and emtricitabine, while K65R is relatively rare in those patients.
Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase.
Result: Analysis of the IC50 values shows that the Lys65Ala mutant is the most susceptible to the inhibitor with an IC50 of 960nM (2-fold increase in susceptibility), while the Lys66 substitution mutants are more similar to the Lys65Arg mutant (Table 3).
Result: However, in this instance the non-conservative mutants show an intermediate resistance profile when compared to WT and Lys65Arg (Supplementary Figures S2).
Result: In an attempt to study the role of Lys66 in drug susceptibility, qualitative gels, and quantitative filter-based drug resistance assays were performed using the various enzymes (WT, Lys66Arg, Lys66Ala, Lys66Asn, Lys66Thr, Lys65Ala and Lys65Arg) in the presenc
Ultrasensitive allele-specific PCR reveals rare preexisting drug-resistant variants and a large replicating virus population in macaques infected with a simian immunodeficiency virus containing human immunodeficiency virus reverse transcriptase.
Result: There were no patients carrying either K65R or T69 insertion.
Discussion: However, some authors have warned about the fact that d4T-based initial therapy in patients infected with subtype C virus selects for a broader array of mutations, including the K65R mutation, conferring resistance to d4T, ddI, ABC, 3TC, FTC, and TDF.
HIV mutation literature information.
PMID: 
2012
AIDS (London, England)
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