literature

HIV mutation literature information.

Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens.

PMID: 23840622 2013 PloS one

Abstract: Compared with 720 recipients of a d4T or AZT-containing first-line regimen, the 153 recipients of a TDF-containing first-line regimen were more likely to have the RT mutations K65R (46% vs 4.0%; p<0.001), Y115F (10% vs. 0.6%; p<0.001), L74VI (8.5% vs. 1.8%; p<0.001), and K70EGQ (7.8% vs. 0.4%) and recipients of an ABC-containing first-line regimen were more likely to have K65R (17% vs 4.0%; p<0.001), Y115F (30% vs 0.6%; p<0.001), and L74VI (56% vs 1.8%; p<0.001).

Discussion: Among patients with virological failure on a first-line dual NRTI plus NNRTI regimen, a higher proportion of those who received TDF and/or A

Persistence of HIV-1 transmitted drug resistance mutations.

PMID: 23904291 2013 The Journal of infectious diseases

Table: K65R

Targeting of the purine biosynthesis host cell pathway enhances the activity of tenofovir against sensitive and drug-resistant HIV-1.

PMID: 23922365 2013 The Journal of infectious diseases

Abstract: Moreover, the extensive use of ddI and d4T has led to high frequencies of the K65R mutation, further compromising TFV efficacy.

In vitro cross-resistance profile of nucleoside reverse transcriptase inhibitor (NRTI) BMS-986001 against known NRTI resistance mutations.

PMID: 23979732 2013 Antimicrobial agents and chemotherapy

Abstract: In the site-directed mutagenesis studies, a virus containing a K65R substitution exhibited a 0.4-fold change in 50% effective concentration (EC50) versus the wild type, while the majority of viruses with the Q151M constellation (without M184V) exhibited changes in EC50 versus wild type of 0.23- to 0.48-fold.

Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase.

PMID: 21908397 2012 Nucleic acids research

Abstract: We demonstrated that XMRV RT mutants K103R and Q190M, which are equivalent to HIV-1 mutants that are resistant to tenofovir (K65R) and AZT (Q151M), are also resistant to the respective drugs, suggesting that XMRV can acquire resistance to these compounds through the decreased incorporation mechanism reported in HIV-1.

Result: Another HIV-1 RT mutation, K65R, decreases susceptibility to tenofovir.

Result: Since AZT and tenofovir are potent inhibitors of XMRV (Table 6), we wanted to investigate whether the XMRV RT mutant equivalents of HIV Q151M and K65R (XMRV Q190M and

Reverse transcriptase genotypes in pediatric patients failing initial antiretroviral therapy in Gaborone, Botswana.

PMID: 21972264 2012 Journal of the International Association of Physicians in AIDS Care (Chicago, Ill.

Abstract: Nucleoside reverse transcriptase inhibitor-associated mutation frequencies noted were M184V (n = 41; 91.1%); thymidine analogue mutations (TAMs; n = 20; 44.4%); >1 TAM (n = 9; 20%); TAM-2 pathway (n = 10; 22.2%); TAM-1 pathway (n = 7; 15.6%); TAM-1 and TAM-2 pathways (n = 3; 6.7%); K65R (n = 2; 4.4%); Q151M (n = 1; 2.2%); and L74V (n = 0; 0%).

Replication-independent expression of anti-apoptosis marker genes in human peripheral blood mononuclear cells infected with the wild-type HIV-1 and reverse transcriptase variants.

PMID: 22239233 2012 Viral immunology

Abstract: Compared with WT, a significant decrease in RCs of viruses: K65R (RC=0.39+-0.02; p<=0.0001), M184V (RC=0.72+-0.04; p<=0.0001), PSD5.1 (RC=0.32+-0.04; p<=0.0001), and PSD5.2 (RC=0.90+-0.04; p=0.002) was observed on day 10.

Abstract: Point mutant K65R showed a 1.5- to 4-fold upregulation of six AAMGs on day 7.

Abstract: The viruses containing patient-derived MDR RT without the K65R mutation (PSD5.2) replicated efficiently in comparison to the viruses with MDR RT containing the K65R mutation (PSD5.1), or the single mutations K65R and M184V.

Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy.

PMID: 22293461 2012 Antiviral therapy

Introduction: A large proportion of these patients harboured mutations associated with cross-resistance to most NRTIs (K65R [19%], Q151M [19%] and/or thymidine analogue mutations (TAMs) [56%]), limiting the potential future use of fully susceptible NRTIs.

Introduction: Furthermore, K65R has been observed in a high frequency, which is linked to nucleotide changes in HIV-1 subtype C.

Introduction: In this setting, consistent resistance data from ART centres reflect a maximum of 39% complex drug resistance patterns (defined as the presence of either K65R and/or Q151M and/or 2 or more thymidine analogue mutations).

Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients.

PMID: 22297391 2012 Antiviral therapy

Abstract: During prolonged viraemia, NRTI resistance increased (n=44, +76%), in particular thymidine analogue mutations (from 4 to 14) and K65R (from 3 to 6).

Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing.

PMID: 22355307 2012 PloS one

Abstract: The most common UDS-detected DRM were NRTI in 18 subjects: M184V/I (11), TAMs(7) & K65R(4); PI DRMs were detected in 9 subjects: M46I/V(5), F53L(2), I50V(1), D30N(1), and N88S(1).

Result: Four patients had a K65R at virologic failure (variant range 0.52% to 1.28%), and none developed phenotypic resistance to TDF (Table S1).

Result: Nineteen of 24 (79.2%) had any PI, N(t)RTI and/or Discussion: None of the patients with K65R (all at <2%) developed phenotypic resistance to TDF (See Table S1).

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