Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa.
Result: The most common major PI RAMs observed were M46I and V82A (n = 12; 12%); I54V (n = 10; 10%); I84V and L76V (n = 7; 7%); I47A/V (n = 3; 3%); I50L/V (n = 2; 2%); and V32I (n = 2; 2%) (Table 1).
Table: L76V
Discussion: Our findings are in agreement with study where major PI RAMs were observed in 5% of patients; among them, V82A 65% (28/43), I54V 63% (27/43), L76V 23% (10/43), and L90M 16% (7/43) were the most frequent.
Discussion: The group recei
Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors.
Abstract: Finally, we show that L76V and N88S changes the hydrogen bond stability of these residues with residues D30/K45 and D30/T31/T74, respectively.
Abstract: For the primary mutation L76V, however, the presence of a background mutation M46I in our analysis influences whether the unfavourable effect of L76V on inhibitor binding is sufficient to outweigh the accompanying reduction in catalytic activity of the protease.
Abstract: In this study, mutations N88S and L76V, along with three other resistance-associated mutations, M46I, I50L, and I84V, are analysed by means of molecular dynamics simulations to in
Multiple Molecular Dynamics Simulations of the Inhibitor GRL-02031 Complex with Wild Type and Mutant HIV-1 Protease Reveal the Binding and Drug-Resistance Mechanism.
Abstract: On the basis of detail analysis of the simulations, we revealed key characteristics that constitute the drug resistance of four mutation HIV-1 proteases toward GRL-02031: substitution of the side chain in these four mutation residues leads to a change in the distances between the flaps and catalytic sites, thereby reducing the affinity for GRL-02031 with these four mutation proteases, even though the L76V and N88D residues cannot directly contact GRL-02031.
Abstract: To elucidate the binding mechanism of HIV-1 protease with promising inhibitor GRL-02031 and further to probe the resistance mechanism associated with mutations (I47V, L76V, V82A, and N88D) to the inhibitor, we
Molecular Genetics and the Incidence of Transmitted Drug Resistance Among Pre-Treatment HIV-1 Infected Patients in the Eastern Cape, South Africa.
Abstract: Four major protease inhibitor (PI) related mutations (I54V, V82A/L, L76V and L90M) were observed in seven patients while several other minor and accessory PIs were also identified.
Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population.
Method: Participants with a history of genotypic/phenotypic drug resistance to protease inhibitors (PIs) or with HIV-1 genotypic drug resistance to PIs at baseline (including D30N, M46I/L, I47V/A, G48V, I50L, I54M/L, Q58E, T74P, L76V, V82A/F/L/T/S, N83D, I84V, N88S, or L90M) were excluded, despite any reported effects of PI resistance or resistance
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: L76V
Characterisation of protease resistance mutations in a South African paediatric cohort with virological failure, 2011 - 2017.
Abstract: Four HIV-1 protease (PR) inhibitors, clinical inhibitors lo
Result: No neutron crystal structures have been reported for the inhibitor complexes in this study; hence, hydrogen bonds for L76V complexes are described by the same criteria as for previously published wild-type complexes (Figure 3).
Result: Once again, the lack of significant differences in PR active-site interactions with 4 indicates that the resistance mechanism induced by L76V relies on an alternate strategy.
Result: Therefore, mutation L76V does not produce major alterations in the overall structure of the PR dimer.
Result: These higher Ki values imply that L76V confers resistance toward the four tested inhibitors.
HIV mutation literature information.
PMID: 
2020
Virology journal
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