Abstract: The mutant HIV PR, which evolved in response to treatment with the potent inhibitor TL-3, contains six point mutations relative to the wild-type enzyme (L24I, M46I, F53L, L63P, V77I, V82A).
Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease.
PMID: 17696515
2007
Journal of medicinal chemistry
Abstract
Abstract: PR(D30N) and PR(V82A) showed compensating interactions with inhibitor 1 relative to those of PR, while reduced hydrophobic contacts were observed with PR(I50V) and PR(I84V).
Abstract: Compound 1 had inhibition constants of 17-fold, 8-fold, 3-fold, and 3-fold, respectively, for PR(D30N), PR(I50V), PR(V82A), and PR(I84V) relative to wild type PR.
Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments.
Abstract: In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]).
Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil.
PMID: 17962868
2007
The Brazilian journal of infectious diseases
Abstract: There was a significant increase in resistance mutations V82A/F/L/T, I84V, L90M, M41L, K70R, L210W, T215Y/F and K219Q/E in MF.
Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice.
Figure: NL4-3 PRI54V+V82A is hypersensitive to bevirimat in PHA-activated PBMCs with 50% inhibitory concentration (IC50) >100 times lower than for wild-type NL4-3.
Figure: The protease mutant is deficient in CA-SP1 cleavage and is comparable to bevirimat-treated wild-type virus, however, the drug has a more dramatic effect on CA-SP1 cleavage in HIV-1 PRI54V+V82A.
Figure: Wild-type NL4-3 and protease mutant NL4-3 PRI54V+V82A virions were collected from transfected 293T cells grown in the presence (20 microM) or absence of bevirimat and analyzed for particle
Predictive factors for response to a boosted dual HIV-protease inhibitor therapy with saquinavir and lopinavir in extensively pre-treated patients.
Abstract: CONCLUSIONS: Baseline HIV-1 RNA < 5.0 log10 and CD4+ T-cell count > 200 cells/microl, lopinavir C(min)GIQ(arch) > 2,000 ng/ml and the absence of viral resistance mutations at V82T/A/F/I/S and 154M/V/L are highly predictive for therapeutic success of a regimen of saquinavir/lopinavir/ ritonavir without RTI in a heterogenic cohort of patients with an extensive pre-treatment history and highly variable pharmacokinetics.
Abstract: Covariates for the decrease of HIV-1 RNA from baseline to week 48 were baseline HIV-1 RNA (P < 0.001), lopinavir C(min)GIQ(arch) (P = 0.013), presence/absence of mutations at V82T/A/F/I/S or 184A/V plus L10I/R/V/F, 154M/V/L or L63P (P = 0.018), and previously taken antiretrovirals (P = 0.034).
Abstract: RESULTS: The analyses de
Structural insights into the mechanisms of drug resistance in HIV-1 protease NL4-3.
Abstract: We have also obtained the crystal structures of three mutant forms of NL4-3 protease containing one (V82A), three (V82A, M46I, F53L) and six (V82A, M46I, F53L, V77I, L24I, L63P) point mutations in complex with TL-3.
A multivariate analysis of HIV-1 protease inhibitors and resistance induced by mutation.
PMID: 16426053
2006
Journal of chemical information and modeling
Abstract: This paper describes the use of the multivariate statistical procedure principal component analysis as a tool to explore the inhibitory activity of classes of protease inhibitors (PIs) against HIV-1 viruses (wild type and more-frequent single mutants, V82A, V82F, and I84V) and against protease enzymes.
Non-infectious fluorimetric assay for phenotyping of drug-resistant HIV proteinase mutants.
Abstract: RESULTS: We cloned a set of GFP-PR reporters, some of which possess a simple, well-defined drug-resistant PR mutant (G48V L90M, V82A, A71V V82T I84V, D30N, K45I); another four complex PR mutants were obtained from patients undergoing HAART.
HIV mutation literature information.
PMID: 
2007
Acta crystallographica. Section D, Biological crystallography
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