Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-10-12
pubmed:abstractText
The non-nucleoside reverse transcriptase inhibitors (NNRTIs) directly inhibit the HIV-1 reverse transcriptase (RT) by binding in a reversible and non-competitive manner to the enzyme. The currently available NNRTIs are nevirapine, delavirdine, and efavirenz; other compounds are under evaluation. NNRTIs are extensively metabolized in the liver through cytochrome P450, leading to pharmacokinetic interactions with compounds utilizing the same metabolic pathway, particularly PIs, whose plasma levels are altered in the presence of NNRTIs. NNRTIs are drugs with a low genetic barrier, i.e. a single mutation in RT genoma induces a high-level of phenotypic resistance, preventing the use of NNRTIs as monotherapy. In naive patients, several trials have shown the value of NNRTIs in combination with nucleosides and/or protease inhibitors. Small pilot studies have shown that NNRTIs may be useful as second-line therapy. However, due to the rapid emergence of resistant virus to these compounds in case of incomplete viral suppression, NNRTIs should not be added to current failing antiretroviral regimen. The most common side-effect reported with nevirapine and delavirdine is rash. The incidence of rash is rather similar under these two compounds, but severe rash is less frequent with delavirdine. The most common adverse reactions reported with efavirenz are central nervous system complaints such as dizziness. Rash is reported less frequently than with nevirapine or delavirdine, and is usually mild. NNRTIs resistance mutations are located in the amino acid residues aligning the NNRTI-binding "pocket" site. High-level resistance is often associated with a single point mutation which develops within this site (especially codon groups 100 - 108 and 181 - 190). Patients failing on one NNRTI are very likely to possess multiple NNRTI resistance mutations. NNRTIs should always be used as part of a potent antiretroviral therapy to insure suppression of viral replication, thus circumventing the rapid selection of cross-resistant variants.
pubmed:language
fre
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0003-410X
pubmed:author
pubmed:issnType
Print
pubmed:volume
151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
260-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
[Non-nucleoside reverse transcriptase inhibitors].
pubmed:affiliation
Service de Médecine Interne, Hôpital Bichat, 75877 Paris Cedex 18.
pubmed:publicationType
Journal Article, English Abstract, Review