Result: Other interesting clusters evidencing PDR transmission within the network included cluster PI-1, with 29 nodes, all men with PI resistance and median age 24 (22-28) enrolled across all years; cluster NRTI-1, with 23 nodes, 22 cisgender men and 1 cisgender woman, with median age 22 (10-27) and constant growth across all years; cluster complex-1, with 10 nodes, all men enrolled from 2018 to 2020 and median age 23 (20-30), 60% (6/10) with PI + NRTI + NNRTI resistance and 40% (4/10) with PI + NRTI resistance; and complex-2, with 7 nodes, all men with median age 26 (21-31) sharing PR M46I, L90M,
Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China.
Result: All individuals in two of the CRF07_BC clusters carried Q58E (PI mutations, N = 29) and 52.6% (10/19) in the other CRF07_BC clusters carried K103N (NNRTI mutations).
Result: Of all clusters, 96.4% (53/55) of individuals with TDR mutation in these clusters were MSM and only two (in clusters with M46L and K103N) were infected through heterosexual transmission (HST) (Figure 4).
Result: Transmitted drug resistance mutations detected in more than 10 cases included PI [Q58E (n = 51) and M46ILV (n = 46)] and NNRTI [K103N (n = 26), E138AGKQ
Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection.
Abstract: Importantly, doravirine remains active against K103N viruses in vitro, and limited clinical evidence suggests this to be the case in patients as well.
Abstract: Since K103N is by far the most prevalent (<70%) NNRTI substitution found in clinical practice, resistance against doravirine-based antiretroviral therapies is expected to be rare, even for treatment-experienced individuals.
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, <
Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China.
Discussion: Discussion: G190A caused high-level resistance to NVP and intermediate resistance to EFV and could result in attenuation of the resistance that occurs with K103N alone, and G190A had a higher frequency (83.47%) of drug resistance in the HIV-1 CRF 01AE subtype in this study.
Discussion: K103N/S (41.32%) was the most frequently observed resistance mutation in NNRTIs, followed by Y181C(27.83%) and G190A(26.21%), This is a consequence of the frequent use of NNRTI-based (EFV/NVP) first-line therapy for more than a decade in China, and these results are similar to the data from low- and middle-income countries.
Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort.
Result: Of the four false-negative results, three were K103N/S (at 10.5, 11.9, and 22.4% mutant frequency) and one at G190A (at 20.59% mutant frequency).
Result: There were no IND results at K103N/S and M184V.
Discussion: K102Q/R, K103R, and K104R have not been associated with reduced susceptibility to NNRTIs, but can interfere with detection of K103N by OLA-Simple, as their presence could interfere with the DNA ligase requirement that the four nucleotides surrounding the ligation site have perfect complementarity with the target, causing an IND result.
Discussion: Probe design for K103N proved particula
Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs.
5Result: As shown in Figure 5A-C, B4 efficiently occupied the pockets of the single amino acid mutations K103N and E138K and the double mutants F227L + V106A with an approximately ""U"" conformation, which was one of the essential condition for the antiviral activity in the DAPY scaffold."
5Result: Docking of B4 with K103N + Y181C predicted that several common features (""U"" binding conformation, hydrogen bonds, and pi-pi stacking interactions) would be lost, which might contribute
Abstract: Moreover, these two compounds had EC50 values of 0.06 and 0.08 muM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC50 = 0.08 muM).
Characterization of viral rebounds on dual etravirine/raltegravir maintenance therapy (ANRS-163 ETRAL trial).
PMID: 32259255
2020
The Journal of antimicrobial chemotherapy
Abstract: For the first patient with VF, UDS detected minority resistant variants only in RT (K103N, 9.6%; Y181C, 4.9%) at baseline.
Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa.
Abstract: The most frequent non-nucleoside reverse transcriptase inhibitor (NNRTI) RAM was K103N/S (40/96, 42%).
Result: We observed that the K103N/S mutation occurred in 41 (43%) of those patients failing cART.
Table: K103N/S
Discussion: The K103N mutation occurred at a higher frequency in patients receiving AZT plus 3TC or ABC plus 3TC than in those receiving TDF plus 3TC, and 3TC plus d4T.
Discussion: The high rate of K103N RAM is also well documented and has been observed in several previous studies.
HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016.
Abstract: The leading DRMs observed in the study were M184I/V (59.59%) against NRTIs and K103N (37.55%) against NNRTIs.
Result: K103N (37.55%, 92/245) was the most frequent mutation, followed by G190A/E/K/Q/S/V (28.57%, 70/245), V179I/D/E/T (27.76%, 68/245), V106A/I/M (26.12%, 64/245), Y181C/V (18.78%, 46/245), K101E/H/P (14.69%, 36/245), Y188C/H/L (5.71%, 14/245), L100I (4.08%, 10/245), and M230L (4.08%, 10/245).
Characteristics of drug resistance in HIV-1 CRF55_01B from ART-experienced patients in Guangdong, China.
PMID: 32300784
2020
The Journal of antimicrobial chemotherapy
Abstract: Among DRMs, M184V (43.83%) was the most frequent NRTI DRM, followed by K65R (23.46%), and V179E (98.77%) was the most frequent NNRTI DRM, followed by K103N (47.53%) and Y181C (14.81%).
HIV mutation literature information.
PMID: 
2021
Pathogens (Basel, Switzerland)
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