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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-4-25
pubmed:abstractText
The inhibitory quotient (IQ) of human immunodeficiency virus (HIV) protease inhibitors (PIs), which is the ratio of drug concentration to viral susceptibility, is considered to be predictive of the virological response. We used several approaches to calculate the IQs of amprenavir and lopinavir in a subset of heavily pretreated patients participating in the French National Agency for AIDS Research (ANRS) 104 trial and then compared their potentials for predicting changes in the plasma HIV RNA level. Thirty-seven patients were randomly assigned to receive either amprenavir (600 mg twice a day [BID]) or lopinavir (400 mg BID) plus ritonavir (100 or 200 mg BID) for 2 weeks before combining the two PIs. The 90% inhibitory concentration (IC(90)) was measured using a recombinant assay without or with additional human serum (IC(90+serum)). Total and unbound PI concentrations in plasma were measured. Univariate linear regression was used to estimate the relation between the change in viral load and the IC(90) or IQ values. The amprenavir phenotypic IQ values were very similar when measured with the standard and protein binding-adjusted IC(90)s. No relationship was found between the viral load decline and the lopinavir IQ. During combination therapy, the amprenavir and lopinavir genotypic IQ values were predictive of the viral response at week 6 (P = 0.03). The number of protease mutations (< 5 or > or = 5) was related to the virological response throughout the study. These findings suggest that the combined genotypic IQ and the number of protease mutations are the best predictors of virological response. High amprenavir and lopinavir concentrations in these patients might explain why plasma concentrations and the phenotypic IQ have poor predictive value.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-10546858, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-11120940, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-11964541, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-12543665, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-12662123, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-12830416, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-14585213, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-14749547, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-15060509, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-15097152, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-15117450, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-15236618, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-15362663, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-15456093, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-15509183, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-15561845, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-15855487, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16173015, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16254964, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16280255, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16372824, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16418700, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16430193, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16554246, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16575741, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16603863, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16640095, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-16856615, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-17296739, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285478-7594659
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1098-6596
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1642-6
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18285478-Adult, pubmed-meshheading:18285478-Aged, pubmed-meshheading:18285478-Carbamates, pubmed-meshheading:18285478-Dose-Response Relationship, Drug, pubmed-meshheading:18285478-Drug Administration Schedule, pubmed-meshheading:18285478-Drug Therapy, Combination, pubmed-meshheading:18285478-Female, pubmed-meshheading:18285478-France, pubmed-meshheading:18285478-Genotype, pubmed-meshheading:18285478-HIV Infections, pubmed-meshheading:18285478-HIV Protease Inhibitors, pubmed-meshheading:18285478-HIV-1, pubmed-meshheading:18285478-Humans, pubmed-meshheading:18285478-Lopinavir, pubmed-meshheading:18285478-Male, pubmed-meshheading:18285478-Middle Aged, pubmed-meshheading:18285478-Phenotype, pubmed-meshheading:18285478-Prognosis, pubmed-meshheading:18285478-Pyrimidinones, pubmed-meshheading:18285478-RNA, Viral, pubmed-meshheading:18285478-Ritonavir, pubmed-meshheading:18285478-Sulfonamides, pubmed-meshheading:18285478-Treatment Outcome, pubmed-meshheading:18285478-Viral Load
pubmed:year
2008
pubmed:articleTitle
Predictive values of the human immunodeficiency virus phenotype and genotype and of amprenavir and lopinavir inhibitory quotients in heavily pretreated patients on a ritonavir-boosted dual-protease-inhibitor regimen.
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