Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa.
Result: Among the key DRMs for PIs, I50 V (0.3%, 1/322) conferred intermediate resistance and I47 V (0.3%, 1/322) conferred low-level resistance.
HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016.
Result: One patient infected with CRF07_BC recombinant subtype showed M46I, I47A, and I50V 3 primary mutations, which was predicted to be resistant to all PIs.
Discussion: Three primary mutations M46I, I47A, and I50V resistant to PIs were detected in one patient, whose regimen was 3TC+AZT+NVP then switched to LPV/r+3TC+TDF.
Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I.
PMID: 31430369
2019
The Journal of antimicrobial chemotherapy
Method: Primary PI-R substitutions were D30N, V32I, M46I/L, I47V/A, G48V, I50V/L, I54M/L, Q58E, T74P, L76V, V82A/F/L/S/T, N83D, I84V, N88S and L90M in PR.
Table: I50V
Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population.
Result: A71V, a compensatory mutation that is far from the active site and almost always observed with I50V, restores the functionality to WT level (Km = 73 +- 9 muM), as previously reported.
Result: A similar repacking was also observed in the I50V-DRV structure, where increased packing against I47 in both chains compensated lost vdW interactions at residue 50.
Result: A time-course gel shift assay confirmed the catalytic activity of I50V single mutant, and the rescued activity of I50V/A71V variant in cleaving purified Gag polyprotein [Figure S1].
Result: Against I84V and I50V mutations, which are located directly at the pocket where P1' moiety binds, UMass1 experie
Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance.
Introduction: One such example is the A71V mutation, a secondary mutation that, when observed in conjunction with I50V/L, acts to restore a balance between catalytic efficiency and inhibitor binding.
Introduction: Primary drug resistant mutations, such as I50V and I84V, occur proximal to the active site and impact inhibitor binding by altering the direct interactions between the protease and inhibitor.
Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance.
Discussion: In contrast, a set of data compiled for NDA21-976/S003 and NDA21-976/S004 clearly indicates that 10 amino acid substitutions including L10F, V32I, L33F, S37N, M46I, I47V, I50V, L63P, A71V, and I84V are the most prevalent (https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021976s003s004lbl.pdf).
HIV mutation literature information.
PMID: 
2020
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