PubMed · 14596252
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
2003. Preclinical data released on PI.. https://pubmed.ncbi.nlm.nih.gov/14596252/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
BACKGROUND: HIV proviral sequencing overcomes the limit of plasma viral load requirement by detecting all the 'archived mutations', but the clinical relevance remains to be evaluated. METHODS: We included 25 participants with available proviral sequences (both intact and defective sequences available) and utilized the genotypic sensitivity score (GSS) to evaluate the level of resistance in their provirus and plasma virus. Defective sequences were further categorized as sequences with and without hypermutations. Personalized GSS score and total GSS score were calculated to evaluate the level of resistance to a whole panel of antiretroviral therapies and to certain antiretroviral therapy that a participant was using. The rate of sequences with drug resistance mutations (DRMs) within each sequence compartment (intact, defective and plasma viral sequences) was calculated for each participant. RESULTS: Defective proviral sequences harbored more DRMs than other sequence compartments, with a median DRM rate of 0.25 compared with intact sequences (0.0, P = 0.014) and plasma sequences (0.095, P = 0.30). Defective sequences with hypermutations were the major source of DRMs, with a median DRM rate of 1.0 compared with defective sequences without hypermutations (0.042, P < 0.001). Certain Apolipoprotein B Editing Complex 3-related DRMs including reverse transcriptase gene mutations M184I, E138K, M230I, G190E and protease gene mutations M46I, D30N were enriched in hypermutated sequences but not in intact sequences or plasma sequences. All the hypermutated sequences had premature stop codons due to Apolipoprotein B Editing Complex 3. CONCLUSION: Proviral sequencing may overestimate DRMs as a result of hypermutations. Removing hypermutated sequences is essential in the interpretation of proviral drug resistance testing.
Relationship between the topological indices and anti-HIV activity of Dihydro (alkylthio) (naphthylmethyl) oxopyrimidines has been investigated. Three topological indices--the Wiener's index--a distance-based topological index, molecular connectivity index--an adjacency based topological index and eccentric connectivity index--an adjacency-cum-distance based topological index were used for the present investigations. A data set comprising of 67 analogues of dihydro (alkylthio) (naphthylmethyl) oxopyrimidine (S-DABO) was selected for the present investigations. The values of the Wiener's index, molecular connectivity index and eccentric connectivity index for each of the 67 compounds comprising the data set were computed using an in house computer program. Resultant data were subsequently analyzed and suitable models were developed after identification of active ranges. Subsequently, a biological activity was assigned to each compound using these models, which was then compared with the reported anti-HIV activity. The use of models based upon these topological indices resulted in prediction of anti-HIV activity with an accuracy ranging from 86% to 89%.
A reversed phase high performance liquid chromatography method was developed for the simultaneous quantitative determination of the nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine, didanosine, stavudine, zidovudine and abacavir in plasma. The method involved solid-phase extraction with Oasis MAX cartridges from plasma, followed by high performance liquid chromatography with a SymmetryShield RP 18 column and ultraviolet detection set at a wavelength of 260 nm. The assay was validated over the concentration range of 0.015-5 mg/l for all five NRTIs. The average accuracies for the assay were 92-102%, inter- and intra-day coefficients of variation (CV) were <2.5% and extraction recoveries were higher than 97%. This method proved to be simple, accurate and precise, and is currently in use in our laboratory for the quantitative analysis of NRTIs in plasma.