Linked Life Data

9222047

Source:http://linkedlifedata.com/resource/pubmed/id/9222047

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1997-8-26
pubmed:abstractText
We examined the phenotypic and genotypic properties of virus from the peripheral blood mononuclear cells (PBMC) and plasma of eight HIV-1-infected asymptomatic patients before and during monotherapy with the proteinase inhibitor saquinavir. Susceptibility of primary isolates to drug was assessed in PBMC culture by deriving IC50 and IC90 values. The observed increases in IC50 and IC90 after approximately one year of therapy with a dosage of 600 mg tds suggests the presence of virus resistant to saquinavir in vivo. The magnitude of this altered susceptibility ranged from three-fold to in one case 100-fold. In two patients a greater than eight-fold decrease in susceptibility to saquinavir was observed. Sequencing of the proteinase genes in viral RNA obtained from patient plasma and/or PBMC was carried out by PCR in parallel with sensitivity testing. In each case between nine and 12 clones were analysed. In the two patients from whom virus had greater than eight-fold reduction in susceptibility, a point mutation was observed in the viral proteinase (Leu90--> Met/Ile). Further mutations were observed at residues 36, 71 and 84 in these subjects. In a third patient, in whom an eight-fold increase in HIV IC50 of saquinavir was observed, no mutations were detected in the proteinase; sequencing of proteinase cleavage sites in viral gag-pol revealed no significant mutations. In no patient was a Gly48-->Val mutation observed, although this has been associated with resistance in vitro. The Leu90-->Met mutation was observed in five subjects, but a greater than eight-fold phenotypic change in antiviral susceptibility was seen in only two of these. Hence, in vivo, the Leu90-->Met but not the Gly48-->Val mutation is necessary, but not sufficient, for phenotypic resistance to saquinavir in HIV.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0305-7453
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
771-9
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Emergence of resistant variants of HIV in vivo during monotherapy with the proteinase inhibitor saquinavir.
pubmed:affiliation
Department of GU Medicine & Communicable Diseases, Imperial College School of Medicine at St Mary's, London, UK.
pubmed:publicationType
Journal Article