HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study.
Result: Four mutations T69D (NRTI), K103N/S (NNRTI), M46I/L (PI) and L90M (PI) showed significantly different percentages in different subtypes (p < 0.05) (Table 1).
Result: Furthermore, we found a very high proportion (29.4%) of PI mutation M46I/L in ART-naive individuals, significantly higher than that in ART-treated individuals (1.3%).
Result: In contrast, most M46I/L variants in other subtypes were scattered within the strains without this mutation, implying natural polymorphism of HIV-1.
Result: Low percentages of NRTI and
Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations.
Result: M46I and I54V mutations co-occur frequently in drug resistance.
Result: Adding M46I and I54V mutations to a RTV-resistant mutant was shown to improve catalytic efficiency while sustaining resistance.
Result: PRS5B contains a second flap mutation M46I, which is a drug resistance mutation for all clinical PIs except DRV, SQV and TPV.
Result: The side chain of flap residue 46 is adjacent to Phe53 at the protein surface, however, the shorter hydrophobic side chain of M46I shows no significant effects on the flap structure of PRS5B inhibitor complexes.
Result: The side chains of flap mutations M46I and I54V do not form van der Waals contacts with these inh
Pretreatment HIV drug resistance spread within transmission clusters in Mexico City.
PMID: 31819984
2020
The Journal of antimicrobial chemotherapy
Result: Other frequently shared DRMs included: reverse transcriptase (RT) Y188L (11/175), RT T215S/C (24/175) and protease M46I (19/175), mostly at >=20% within-host frequency; and RT D67N/G/E (56/175) and RT P225H (16/175) as low-frequency variants.
Result: The most frequent PI mutations included M46I/L and L90M.
Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya.
PMID: 33654530
2020
The Pan African medical journal
Introduction: At the coastal region of Kenya, L90M, M46I and D30N mutations conferring resistance to PIs were identified among out-patients injecting drug users.
Table: M46I
Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China.
Result: PI resistance were detected in only two samples, being simultaneously resistant to ATV/r and LPV/r at a potential low level caused by M46I/L mutation.
Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia.
Result: Also, one Croatian patient with a complex pattern of resistance (SDRM to PI: I84V + NRTI: M184MIV, T215S, L210W + NNRTI: K101E, Y181C, G190A, P225PH) was observed in a transmission pair with a Serbian sequence with a similar SDRM pattern with one additional SDRM (PI: M46I), indicating cross border transmission of multi-class drug resistance.
Discussion: For mutations M46I, T69D, G190E,
Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort.
Result: A Kaplan-Meier analysis could be performed for 18 TDRMs (K20T, L23I, K43T, M46I/L/V, I54V, M41L, L74I, M184V, L210W, K219R, T215A/C/D/N/S and T215Y).
Discussion: In concordance with the three other studies on the persistence of TDRMs, for most PI mutations (I54V, K43T, L23I, M46I/L/V) a long mean survival time between 2.2 and 4.2 years was found in our st
High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014.
PMID: 30640198
2019
The Pediatric infectious disease journal
Result: One child had a major M46I PI mutation, which causes low level of resistance to all PIs except darunavir and tipranavir, and another had the I50L major PI mutation, which causes high level resistance to atazanavir (Table 1).
Evolution of Protease Inhibitor Resistance in Human Immunodeficiency Virus Type 1 Infected Patients Failing Protease Inhibitor Monotherapy as Second-line Therapy in Low-income Countries: An Observational Analysis Within the EARNEST Randomized Trial.
HIV mutation literature information.
PMID: 
2020
AIDS research and therapy
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