Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients.

Details

Serval ID
serval:BIB_84CEAFA7373C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients.
Journal
AIDS
Author(s)
Marzolini C., Telenti A., Decosterd L.A., Greub G., Biollaz J., Buclin T.
ISSN
0269-9370
Publication state
Published
Issued date
2001
Peer-reviewed
Oui
Volume
15
Number
1
Pages
71-75
Language
english
Abstract
OBJECTIVE: Limited information exists on the clinical usefulness of drug level monitoring for efavirenz, a once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI). The aim of this study was to determine whether efavirenz plasma concentration monitoring could predict treatment failure and central nervous system (CNS) tolerability. METHODS: Blood samples were obtained from 130 HIV-infected patients receiving efavirenz in combination with other antiretroviral agents for more than 3 months. Efavirenz plasma concentrations were measured by high-performance liquid chromatography. An evaluation of CNS side-effects was performed and the viral load, CD4 cell count and other clinical and laboratory data were assessed. In 85 patients, these measures were repeated at 3 month intervals. RESULTS: Efavirenz plasma levels (n = 226) were measured at an average of 14 h after drug intake. Drug concentrations ranged from 125 to 15230 microg/l (median 2188). Large inter-patient (CV 118%) and limited intra-patient (CV 30%) variabilities were observed in efavirenz levels. Virological failure was observed in 50% of patients with low efavirenz levels (< 1000 microg/l) versus 22 and 18% in patients with 1000-4000 microg/l or more than 4000 microg/l, respectively. CNS toxicity was approximately three times more frequent in patients with high efavirenz levels (> 4000 microg/l) compared with patients with 1000-4000 microg/l. CONCLUSION: Treatment failure and CNS side-effects are associated with low and high efavirenz plasma levels, respectively. The important inter-individual variability in efavirenz levels strongly argues for dose adjustment on the basis of therapeutic drug monitoring to optimize treatment.
Keywords
Adult, Aged, Anti-HIV Agents, Benzoxazines, Central Nervous System, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Oxazines, Predictive Value of Tests, Reverse Transcriptase Inhibitors, Treatment Failure, Viral Load
Pubmed
Web of science
Create date
25/01/2008 10:41
Last modification date
20/08/2019 14:44
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