Abstract: Compared to rHIVWT, rHIVV32I was highly susceptible to DRV and had significantly reduced fitness, explaining why V32I did not emerge upon selection of rHIVWT with DRV.
Abstract: Here, we show that the preexistence of certain single amino acid substitutions such as V32I, I54M, A71V, and I84V in HIV-1 protease facilitates the development of high-level DRV resistance.
Abstract: However, wild-type HIVNL4-3 (rHIVWT) failed to acquire V32I and did not develop DRV resistance.
Abstract: Interestingly, all in vitro-selected highly DRV-resistant HIV-1 variants acquired V32I but never emerged in wild-type HIV (HIVWT), and V32I itself rendered HIV-1 more sensitive to DR
Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease.
Result: Similar effects were observed for the neutron structure of amprenavir complexed with PR mutant V32I/I47V/V82I.
Discussion: Interestingly, five of the seven residues adjacent to Leu76 in the PR structure are sites of major resistance mutations, D30N, V32I, I47V, Q58E, and T74P2.
Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir.
Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults.
PMID: 28328546
2017
Journal of acquired immune deficiency syndromes (1999)
Result: The most common PI mutations were V82A/T/F/S/I; V32I mutation was present in 3 cases, and has been associated with high level of resistance in combination with other PI mutations.
Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K.
PMID: 28195728
2017
Journal of medicinal chemistry
Method: The PRTM has substitutions V32I, I47V and V82I associated with drug resistance, which are in addition to five stabilizing substitutions Q7K, L33I, L63I, C67A and C95A.
Result: From a detailed analysis of the two XN structures it is evident that drug resistant substitutions V32I, I47V and V82I, which add or remove a CH3 group on the side chains, do not significantly alter the hydrophobic contacts.
Result: Previously, the observation of DRV disordered over two orientations by a 180 flip did not allow us to observe any H atoms in the 0.84 A ultra-high resolution X-ray structure of PMID: 28750647
2017
AIDS research and therapy
Result: Two (3.0%) subjects harbored major PI DRM (D30N, M46I and V32I).
Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128).
Introduction: The latest International AIDS Society (IAS)-USA panel list shows 11 mutations associated with DRV resistance: V11I, V32I, L33F, Result: Interestingly, the regions included the two major DRV resistance mutations (I47V and I50V) and one minor mutation (V32I), which were induced by the in vitro selection (Figure 3C).
Result: The major virus (referred to as FS5929R1) had two major DRV resistance mutations (I47V and I50V), four minor mutations (V11I, V32I, L33F, and L89V), and V82F.
Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme.
Result: PR20 cluster 1 encompasses three mutations contiguous to the active site, D30N, V32I and L33F, that are
Result: Although PR20 bears major DRV resistance mutations V32I, I47V, I54L, there are no corresponding mutations in PRS17 to explain the similar Ki values shown by these 2 enzymes.
Result: In contrast, mutations D30N, V32I, L33F, I47V, I54L, and I84V are present in PR20 but not in PRS17.
Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals.