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).
PMID: 29461980
2018
The Journal of clinical investigation
Abstract: The modifying effect of I47V was confined to B*57:01 and was not observed for the closely related B*57:03.
Abstract: Using whole-genome sequencing of untreated B*57+ HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only significant modifier of B*57 protection.
Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran.
PMID: 29026792
2017
Iranian journal of public health
Abstract: The analysis of reverse transcriptase showed M184V (68.9%), T215YISF (44.8%), K103N (27.6%) and the analysis results of protease revealed G73SC (13.8%) and I47VA (6.9%).
Result: For PIs, G73SC and I47VA were observed as the most common minor and major mutations, respectively.
Discussion: I47VA confers high-level resistance to lopinavir and fos
Discussion: Hence, we recommend more studies to investigate the distribution of I47VA mutation at national level to help with development of treatment guidelines.
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).
Method: Primary PI-R substitutions assessed were D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54L/M, Q58E, T74P, L76V, V82A/F/L/S/T, I84V, N88S, and L90M in PR.
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
Abstract: To better understand binding of clinical inhibitors to resistant HIV-1 protease, we used room-temperature joint X-ray/neutron (XN) crystallography to obtain an atomic-resolution structure of the protease triple mutant ( Conclusion: Drug resistant mutations V32I, I47V and V82I do not seem to alter the hydrogen bonding pattern and hydrophobic interactions of amprenavir with the enzyme, even though the 100K X-ray crystal structure of PRTM-APV suggests otherwise.
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.
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: 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.
Result: This difference may relate to major APV drug resistance mutations V32I, I47V, I84V present in PR20 but
Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals.
Result: Protease (PR) RAMs detected from this outlier sample were M46I, I47V and I84V, and reverse transcriptase (RT) RAMs were A62V, D67N, K70R, V75I, F116Y, Q151M and K219Q.
Result: The PR RAMs for this sample were V32I, I47V, I54L, V82A and L90M.
Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance.
Result: Each rFS5929R1 virus without I47V (rFS5929R1I47) and rFS5929R1 without I50V (rFS5929R1I50) exhibited a >175-fold and 96.9-fold increase in DRV resistance, respectively, whereas the rFS5929R1 without the two mutations (rFS5929R1I47/I50) exhibited a 20.4-fold increase.
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
Prevalence of Drug Resistance Associated Mutations Among the Anti Retroviral Therapy Exposed HIV-1 Infected Individuals in Manipur, Northeast India.
Result: Most PI SDRMs were present only as low-abundance variants under the 5% threshold, including L23I, D30N, I47V, I50V, F53L, I54T, G73S, V82A, N83D, I84V, I85V, N88DS, and L90M (Fig 2).
HIV mutation literature information.
PMID: 
2018
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