literature

HIV mutation literature information.

Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection.

PMID: 32180823 2020 Drugs in context

Introduction: Across those clinical isolates (no subtype information was provided), DOR displayed a good antiviral activity with fold changes in EC50<9 against most single mutant viruses, including A98G, E138A/G/K/Q, G190A, K101E/P, K103N/S, L100I, P236L, V106M, V108I, V197D, V90I, Y181C/V, and Y188H/C.

Introduction: The highest levels of reduction in DOR susceptibility were associated with V106A or Y188L or each of these two

Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa.

PMID: 32265875 2020 Frontiers in microbiology

Discussion: The group receiving AZT plus 3TC or ABC plus 3TC showed the highest rates of NNRTI mutations such as P225H, V106M, E138A/G/K/Q, G190A/S, and Y188L occurred most frequently in patients receiving AZT plus 3TC or ABC plus 3TC.

HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016.

PMID: 32280691 2020 BioMed research international

Result: E138A/G/R/K/Q was found in this case and was predicted to have low/potential resistance to RPV and ETR.

Privileged scaffold inspired design of novel oxime-biphenyl-DAPYs in treatment of HIV-1.

PMID: 32334191 2020 Bioorganic chemistry

Abstract: Compound 7d was found to be the most potent one against both wild type (EC50 = 12.1 nM) and E138K mutant strains (EC50 = 0.0270 microM).

Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding.

PMID: 32379830 2020 PloS one

Introduction: Genetic resistance pathways including primary mutations at codons Y143C/H/R, Q148H/K/R or N155H together with one or more additional associated secondary mutations at L74M, E92Q, T97A, E138E/A/K or G140S/A, has been reported to result in higher levels of resistance with RAL treatment.

Table: E138K

Discussion: Furthermore, Xue and team found that the cross-resistance mutation E138K/Q148K resulted in a reduction in the chelation ability of oxygen atoms in INSTIs to Mg2+ in the active site of the mutated intaso

Accumulation of integrase strand transfer inhibitor resistance mutations confers high-level resistance to dolutegravir in non-B subtype HIV-1 strains from patients failing raltegravir in Uganda.

PMID: 32853364 2020 The Journal of antimicrobial chemotherapy

Abstract: Two patients, one with E138A/G140A/Q148R/G163R and one with E138K/G140A/S147G/Q148K, displayed the highest reported resistance to raltegravir, elvitegravir and even dolutegravir.

Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping.

PMID: 32929472 2020 The Journal of antimicrobial chemotherapy

Abstract: Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects.

Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development.

PMID: 32925358 2020 Journal of acquired immune deficiency syndromes (1999)

Introduction: Although RT E138K was observed as with the other subtypes, it was followed by RT K101E to yield the unique double substitution RT E138K/K101E instead of E138K/L100I.

Introduction: By contrast, under the same conditions, RT substitutions L100I and K103N were the major substitutions associated with EFV, and E138K and K101P substitutions were the 2 most common resistance pathways in selection studies with RPV.

Introduction: No viral breakthrough was observed with DOR

Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.

PMID: 32986709 2020 PloS one

Table: E138K

First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens.

PMID: 32843050 2020 Antimicrobial resistance and infection control

Conclusion: Another GRT, covering HIV-1 integrase (IN) region, performed on the sample plasma aliquot, revealed major RAMs, L74I, E138KQ, G140A, Q148R, and E157Q, to integrase strand transfer inhibitors (INSTI) including raltegravir, dolutegravir, bictegravir and elvitegravir.

Discussion: Specifically, previous exposure to RAL (a drug with a low-genetic barrier to resistance) in a context of poor adherence contributed to selecting mutations (E138KQ, G140A, Q148R) conferring cross-resistance to DTG.

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