literature

HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance.

PMID: 32555643 2020 PloS one

Introduction: Patients failing an NNRTI-based first-line regimen with genotypic drug resistance mutations typically present with M184V/I, K65R, and/or thymidine analogue mutations (TAMs) and K103N, Result: A quarter (9/36 [25%]) of the samples contained both M184V and K103N mutations.

Result: Both groups of patients were on similar regimens and displayed similar genotypic resistance profiles, with the K103N (>=57%) and M184V (>=71%) mutations being the most prevalent.

Prevalence and determinants of virological failure, genetic diversity and drug resistance among people living with HIV in a minority area in China: a population-based study.

PMID: 32576136 2020 BMC infectious diseases

Figure: Note: PIs mutations: M46I, I54V, V82A, K20T, L10F/LFI and Q58E/QE; NRTIs mutations: D67N/DN, K70R/KR/T, M184V/MV/I, T215F/FS/TNSY, K219Q, K65R, L74I/LI/LV, Y115F, L210W, M41L and V75I; NNRTIs mutation:

PMID: 32631509 2020 Bioorganic & medicinal chemistry letters

Abstract: In addition, it showed moderate inhibitory potency (EC50 = 1.329 muM) against the HIV-1 K103N/Y181C double mutant strain (MT-4 cells).

Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants.

PMID: 32640577 2020 Viruses

Abstract: Here, we characterize the mode of action of N'-(2-hydroxy-benzylidene)-3,4,5-trihydroxybenzoylhydrazone (compound 13), an N-acylhydrazone derivative that inhibited viral replication (EC50 = 10 microM), while retaining full potency against the NNRTI-resistant double mutant K103N-Y181C virus.

Method: Triplicate wells of 96-well plates containing serial dilutions of drugs were seeded with 3 x 104 MT4 cells and infected with HIV-1 NL4.3 wt or with the HIV-1 NL4-3 K103N-Y181C strain at multiplicity of infection (MOI) of 0.003 or 100 culture infective dose (CCID50) calculated using the Reed and Muench method.

Discussion: Consistently, compound 13 retained full potency of inhibition against the NNRTI drug-resistant HIV-1 strain K103N

Impact of Pre-antiretroviral Therapy CD4 Counts on Drug Resistance and Treatment Failure: A Systematic Review.

PMID: 32655148 2020 AIDS reviews

Abstract: Most frequent resistance mutations included the M184I/V for the nucleoside reverse-transcriptase inhibitors (NRTIs), K103N, and Y181 for the non-NRTIs (NNRTIs), and L90M for the Protease inhibitors.

Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon.

PMID: 32692778 2020 PloS one

Abstract: Fifteen (15) PDR mutations were found among four patients the urban settings [6 resistance mutations to NRTIs:[M41L (2), E44D (1), K65R (1), K70E (1), M184V/I (2), K219R (1)] and 6 resistance mutations to NNRTIs: K103N (1), E138A/G (2), V179E (1), M230L (1), K238T (1), P225H (1)] against two (02) mutations found in two patients in the rural setting[2 resistant mutations to NNRTIs: E138A (1) and

Bioisosterism-based design and enantiomeric profiling of chiral hydroxyl-substituted biphenyl-diarylpyrimidine nonnucleoside HIV-1 reverse transcriptase inhibitors.

PMID: 32712537 2020 European journal of medicinal chemistry

Abstract: Among all the chiral derivatives, (S)-(-)-12a showed the best potency with the antiviral activities against wild-type (WT) and single mutant strains (L100I, K103 N, Y181C, E138K; especially Y188L), and RT enzyme in the low nanomolar concentration range.

Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia.

PMID: 32804970 2020 PloS one

Abstract: The most common NNRTI associated mutation was the K103N (65.5%) which confers resistance to both efavirenz (EFV) and nevirapine (NVP).

Result: Overall, the 10 most common mutations were M184V (81%), K103N (65.5%), Y188C (36.2%), Y181C (36.2%), V106A (36.2), K65R (34.5%), K70RTQNE (32.8%), G190ASV (31.0%), K101EHP (31.0%) and E138AGQ (29.3%).

Result: The ten most common mutations to the drug class NNRTI included

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: Detected RAMs were M41L, K70Q, V75I, Q151M, M184V and T215F for NRTI; K103N and V108I for NNRTI; and L10F, K20I, M36I, M46I, I47V, I54L, L63H, L76V, V82S and L89I for PI/r.

Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia.

PMID: 32874468 2020 Infectious disease reports

Abstract: Drug resistance-related major mutation was not detected in protease fragments of pol gene, but two major mutations, K103N (6.67%) and Y181C (6.67%), were detected in reverse transcriptase fragments of pol gene.

Conclusion: The drug resistance-associated major mutations, K103N (6.67%) and Y181C (7.14%), were detected in RT genes, suggesting the emergence of TDR in Jakarta.

Table: K103N