Linked Life Data

16545009

Source:http://linkedlifedata.com/resource/pubmed/id/16545009

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-3-20
pubmed:abstractText
Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (Cmin) and total drug exposure over 24 hr (AUC24) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the double nonnucleoside study (2NN), which compared the efficacy of NVP and/or EFV together with stavudine and lamivudine. The objective was to find cutoff values of the Cmin and AUC24 below which the risk of virologic failure increased. The relation between Cmin and AUC24 with virologic failure (never a plasma viral load [pVL] < 50 copies/ml or a rebound to two consecutive pVL > 50 copies/ml) was analyzed with proportional hazard analyses. Data were censored at end of study or change of allocated treatment. The risk of virologic failure with NVP (n = 511) started to increase at a Cmin < 3.1 mg/L (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.89-1.97), but there was no cutoff value below which a statistically significant increased risk occurred. Neither was such a cutoff point identified for the AUC24. The risk of virologic failure with EFV (n = 312) was significantly increased at a Cmin < 1.1 mg/L (HR, 1.95; 95% CI, 1.08-3.54) and an AUC24 < 40 mg x hr x L1 (HR, 1.95; 95% CI, 1.07-3.54). Both cutoff values represent the median values for adherent patients. These associations were driven by patients from Thailand. Adjusting for geographical region made the association between Cmin and AUC24 with virologic failure statistically nonsignificant. The sensitivity of the Cmin values was too low (29% for NVP, 64% for EFV) to be an adequate predictor for virologic failure. We conclude that identifying the Cmin value for the sole purpose of predicting virologic failure in patients who report to be adherent to NVP or EFV is questionable because of the absence of a concentration-response relation (NVP) or the low sensitivity for such a cutoff value (NVP and EFV).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0889-2229
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
232-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16545009-Adult, pubmed-meshheading:16545009-Anti-HIV Agents, pubmed-meshheading:16545009-Area Under Curve, pubmed-meshheading:16545009-Benzoxazines, pubmed-meshheading:16545009-Female, pubmed-meshheading:16545009-HIV Infections, pubmed-meshheading:16545009-HIV-1, pubmed-meshheading:16545009-Humans, pubmed-meshheading:16545009-Lamivudine, pubmed-meshheading:16545009-Male, pubmed-meshheading:16545009-Nevirapine, pubmed-meshheading:16545009-Oxazines, pubmed-meshheading:16545009-Patient Compliance, pubmed-meshheading:16545009-Proportional Hazards Models, pubmed-meshheading:16545009-Prospective Studies, pubmed-meshheading:16545009-RNA, Viral, pubmed-meshheading:16545009-ROC Curve, pubmed-meshheading:16545009-Randomized Controlled Trials as Topic, pubmed-meshheading:16545009-Reverse Transcriptase Inhibitors, pubmed-meshheading:16545009-Stavudine
pubmed:year
2006
pubmed:articleTitle
Pharmacokinetic parameters of nevirapine and efavirenz in relation to antiretroviral efficacy.
pubmed:affiliation
International Antiviral Therapy Evaluation Center, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, 1005 Amsterdam, The Netherlands. vanlethf@kncvtbc.nl
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't