Linked Life Data

19853627

Source:http://linkedlifedata.com/resource/pubmed/id/19853627

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-2-1
pubmed:abstractText
HIV protease plays a crucial role in the viral life cycle and is essential for the generation of mature infectious virus particles. Detailed knowledge of the structure of HIV protease and its substrate has led to the design of specific HIV protease inhibitors. Unfortunately, resistance to all protease inhibitors (PIs) has been observed and the genetic basis of resistance has been well documented over the past 15 years. The arrival of the early PIs was a pivotal moment in the development of antiretroviral therapy. They made possible the dual class triple combination therapy that became known as HAART. However, the clinical utility of the first generation of PIs was limited by low bioavailability and high pill burdens, which ultimately reduced adherence and limited long-term viral inhibition. When therapy failure occurred multiple protease resistance mutations were observed, often resulting in broad class resistance. To combat PI-resistance development, second-generation approaches have been developed. The first advance was to increase the level of existing PIs in the plasma by boosting with ritonavir. The second was to develop novel PIs with high potency against the known PI-resistant HIV protease variants. Both approaches increased the number of protease mutations required for clinical resistance, thereby raising the genetic barrier. This review provides an overview of the history of protease inhibitor therapy, its current status and future perspectives. It forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1872-9096
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
59-74
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Fifteen years of HIV Protease Inhibitors: raising the barrier to resistance.
pubmed:affiliation
Dept. of Virology, University Medical Center Utrecht, Utrecht, The Netherlands.
pubmed:publicationType
Journal Article, Review, Historical Article, Research Support, Non-U.S. Gov't