literature

HIV mutation literature information.

Impact on replicative fitness of the G48E substitution in the protease of HIV-1: an in vitro and in silico evaluation.

PMID: 18545158 2008 Journal of acquired immune deficiency syndromes (1999)

Abstract: These simulations documented that the G48E mutant interacted with PI resistance mutations (M46I, I54V, Q58E, and L63P) and with natural polymorphisms specific to subtype A1 (E35D, M36I, and R57K) that were present in the patient's virus.

Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir.

PMID: 18560011 2008 Protein science

Abstract: Furthermore, we analyzed possible interaction of the I47A mutation with secondary mutations V32I and I54V.

Abstract: The crystal structure of the I47A/I54V PR double mutant in complex with LPV shows that the I54V mutation leads to a compaction of the flap, and molecular modeling suggests that the introduction of the I54V mutation indirectly affects the strain of the bound inhibitor in the PR binding cleft.

Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir.

PMID: 18597780 2008 Journal of molecular biology

Abstract: The crystal structures of flap mutants PR(I50V) (PR with I50V mutation), PR(I54V) (PR with I54V mutation), and PR(I54M) (PR with I54M mutation) complexed with saquinavir (SQV) as well as PR(G48V) (PR with G48V mutation), PR(I54V), and PR(I54M) complexed with darunavir (DRV) were determined at resolutions of 1.05-1.40 A.|m

Genotypic resistance analysis of the virological response to fosamprenavir-ritonavir in protease inhibitor-experienced patients in CONTEXT and TRIAD clinical trials.

PMID: 18852278 2008 Antimicrobial agents and chemotherapy

Abstract: The JT procedure led to selecting the CONTEXT/TRIAD genotypic set of mutations, I15V, M46I/L, I54L/M/V, D60E, L63P/T, and I84V, as providing the strongest association with the VR (P = 1.45 x 10(-11)).

Transmission networks of drug resistance acquired in primary/early stage HIV infection.

PMID: 19005274 2008 AIDS (London, England)

Result: In addition, cluster C represents an MDR transmission network, wherein all four PHIs harboured K103N and three of the four also harboured L10I, I54V, A71V, V82A/I/T, I84I/V, and L90M.

Association of Gag cleavage sites to protease mutations and to virological response in HIV-1 treated patients.

PMID: 16875739 2007 The Journal of infection

Abstract: Two patterns of mutations in the protease were identified: (M46I/L, I54V, V82A/T/F) was associated to the A431V and (K20I/R/M, L89M/I) to the S373Q and L449P.

A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism.

PMID: 17227139 2007 PLoS medicine

Method: Primary protease resistance-associated mutations were defined as any change versus wild-type at positions 23, 24, 30, 32, 46, 47, 48, 50, 54, 82, 84, 88, and 90 in the viral protease, with the following exceptions: I54V and N88D (not reported to occur without other primary mutations) and V82I (known polymorphism in PI-naive patients).

Result: In three of the experiments we observed an A431V amino acid substitution in the NC/p1 cleavage site, combined with known resistance substitutions in protease (V32I, M46I/L, I54V, V82A/F,

Interpretation of genotype and pharmacokinetics for resistance to fosamprenavir-ritonavir-based regimens in antiretroviral-experienced patients.

PMID: 17296739 2007 Antimicrobial agents and chemotherapy

Abstract: The Zephir mutation score included 12 IAS protease mutations associated with poorer virological response: L10I/F/R/V, L33F, M36I, M46I/L, I54L/M/T/V, I62V, L63P, A71I/L/V/T, G73A/C/F/T, V82A/F/S/T, I84V, L90M, and polymorphism mutations I13V, L19I, K55R, and L89M.

Unique thermodynamic response of tipranavir to human immunodeficiency virus type 1 protease drug resistance mutations.

PMID: 17360759 2007 Journal of virology

Abstract: Characterization of tipranavir binding to wild-type protease, active site mutants I50V and V82F/I84V, the multidrug-resistant mutant L10I/L33I/M46I/I54V/L63I/V82A/I84V/L90M, and the tipranavir in vitro-selected mutant I13V/V32L/L33F/K45I/V82L/I84V was performed by isothermal titration calorimetry and crystallography.

Tipranavir: a new protease inhibitor for the treatment of antiretroviral-experienced HIV-infected patients.

PMID: 17425479 2007 Expert opinion on pharmacotherapy

Abstract: The TPV mutation score includes L10V, I13V, K20M/R/V, L33F, E35G, M36I, K43T, M46L, I47V, I54A/M/V, Q58E, H69K, T74P, V82L/T, N83D and I84V.

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