Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-5-7
pubmed:abstractText
Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For example, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1567-1348
pubmed:author
pubmed-author:AriyoshiKK, pubmed-author:BouzasM BMB, pubmed-author:BrigidoL FLF, pubmed-author:CahnPP, pubmed-author:CamachoRR, pubmed-author:CamoEE, pubmed-author:CarvalhoA PAP, pubmed-author:ClarkeJJ, pubmed-author:DeforcheKK, pubmed-author:GrossmanZZ, pubmed-author:HarriganP RPR, pubmed-author:HolguinAA, pubmed-author:KantorRR, pubmed-author:KatzensteinD ADA, pubmed-author:MoreauYY, pubmed-author:MorrisLL, pubmed-author:PhanuphakPP, pubmed-author:PillayDD, pubmed-author:RodriguesRR, pubmed-author:RudichHH, pubmed-author:ShaferR WRW, pubmed-author:ShapiroJ MJM, pubmed-author:SilanderTT, pubmed-author:SirivichayakulSS, pubmed-author:SnoeckJJ, pubmed-author:SoaresM AMA, pubmed-author:SorianoVV, pubmed-author:SugiuraWW, pubmed-author:TanuriAA, pubmed-author:Van LaethemKK, pubmed-author:VandammeA-MAM, pubmed-author:WeberJJ, pubmed-author:WynhovenBB
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
382-90
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors.
pubmed:affiliation
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. koen.deforche@gmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't