HIV/AIDS Drug Monitoring: Intraindividual variability in HAART levels limit therapeutic drug monitoring utility

AIDSWEEKLY Plus; Monday, May 22, 2006
Staff Medical Writers

According to recent research published in the journal Clinical Infectious Diseases, "Effective therapeutic drug monitoring for antiretrovirals requires a better understanding of intraindividual variability in pharmacokinetics.

"We determined concentrations of human immunodeficiency virus (HIV) protease and nonnucleoside reverse-transcriptase inhibitors for 10 patients with undetectable plasma HIV RNA levels who had been receiving stable regimens for greater than or equal to11 months."

"Plasma samples were collected at the same time of day 3 times per week for up to 4 months. Patients were instructed to take their antiretrovirals at the same time every day. Plasma protease and nonnucleoside reverse-transcriptase inhibitor concentrations were determined using high-performance liquid chromatographic methods.

"Pharmacokinetic variability was expressed as intraindividual percentage coefficient of variation (ICV), which was calculated as the patient's standard deviation divided by the mean drug concentration for that patient. ICV was determined for 6 drugs for 10 patients, for a total of 17 different patient-drug combinations, using 600 total samples," researchers said.

"ICV was unexpectedly high for most patients who were receiving protease inhibitors (ICVs for individual patients taking lopinavir/ritonavir were 24, 33, 51, and 92%; for patients taking nelfinavir/M8 metabolite, they were 30%/44% and 39%/54%; for patients taking ritonavir, they were 34 and 43%; for patients taking saquinavir, they were 52% and 55).

"ICVs for patients receiving nonnucleoside reverse-transcriptase inhibitors were lower (for patients receiving efavirenz, they were 7%, 13, 29, and 51%; for a patient receiving nevirapine, it was 25%)," R.E. Nettles and colleagues at Johns Hopkins University School of Medicine reported.

Investigators continued, "The median ICV for all patients receiving protease inhibitors (n=12) was 43.5%, and for all patients receiving nonnucleoside reverse-transcriptase inhibitors (n=5), the median ICV was 25%. Intraindividual variability in concentrations of antiretrovirals was surprisingly high in virologically suppressed patients.

"Possible contributors include food effects, concomitant use of prescription and herbal medications, assay variability, or medication timing, which was assessed by self-report."

"High intraindividual pharmacokinetic variability may limit the utility of single measurements in therapeutic drug monitoring for some antiretroviral agents," Nettles concluded.

Nettles and colleagues published their study in Clinical Infectious Diseases (Marked intraindividual variability in antiretroviral concentrations may limit the utility of therapeutic drug monitoring. Clin Infect Dis. 2006 Apr 15;42(8):1189-96).

For additional information, contact C. Flexner, Division Clinic Pharmacology, Osler 503, 600 N Wolfe St., Baltimore, MD 21287, USA.

The publisher's contact information for the journal Clinical Infectious Diseases is: University Chicago Press, 1427 E 60th St., Chicago, IL 60637-2954, USA.

Keywords: Baltimore, Maryland, United States, HIV/AIDS, Intraindividual Pharmacokinetic Variability, Therapeutic Drug Monitoring, Antiretroviral Drugs, Single Measurements.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Nettles RE, Kieffer TL, Parsons T, et al., "Marked intraindividual variability in antiretroviral concentrations may limit the utility of therapeutic drug monitoring", Clin Infect Dis. 2006 Apr 15;42(8):1189-96.

PubMED Related articles Search

060522
AW060511

Copyright © 2006 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA. Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588 http://www.newsrx.net

AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Elton John AIDS Foundation, Bridgestone/Firestone Charitable Trust, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2006. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright © 1980,2006. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content.