Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy.
Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran.
PMID: 23590295
2013
Journal of medicinal chemistry
Introduction: Recently, we characterized a clinically derived HIV-1 protease (PR20) bearing 20 mutations [Q7K, L10F, I13V, I15V, D30N, V32I, L33F, E35D, M36I, S37N, I47V, I54L, Q58E, I62V, L63P, A71V, I84V, N88D, L89T and L90M] and extremely resist
Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan.
Virological response to darunavir in patients infected with HIV is linked to darunavir resistance-associated mutations corrected by the count of mutations with positive impact and is not associated with pharmacological and combined virological/pharmacological parameters.
PMID: 21545648
2012
Fundamental & clinical pharmacology
Abstract: Darunavir GIQ is defined as the ratio between darunavir trough plasma concentration and the count of darunavir resistance-associated mutations (V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, L89V) corrected or not corrected by the count of mutations with positive impact (V82A and E35D).
Abstract: The count of darunavir resistance-associated mutations corrected by the count of V82A and E35D mutations was the single parameter significantly (P = 0.027) associated with virological response.
HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements.
Result: All the PR20 structures show the same large structural change in the flap hinge region (residues 34 to 43) relative to the corresponding wild-type PR structures, which is attributed in part to the E35D, M36I and S37N mutations (Figure 5A).
Result: Although PR20 and MDR769 exhibit similar twisting of the hinge loop due to the M36I mutation, PR20 bears other mutations in the hinge loop, such as I33F and E35D, that can alter the flexibility of its flaps.
Result: Comparison of PR20/p2-NCclosed with the corresponding wild type PR/p2-NC
Monitoring HIV viral load in resource limited settings: still a matter of debate?
Result: Among the more polymorphic PI mutations (nevertheless included in the IAS-USA December 2010 list as PI-resistance mutations) the most prevalent ones were E35D, M36I, L63P and V91S reaching a percentage ranging between 30% and 50%.