Overcoming Obstacles to the Success of Protease Inhibitors in Highly Active Antiretroviral Therapy Regimens
- 1 December 2002
- journal article
- research article
- Published by Mary Ann Liebert Inc in AIDS Patient Care and STDs
- Vol. 16 (12) , 585-597
- https://doi.org/10.1089/108729102761882125
Abstract
Success with current protease inhibitors (PIs) is limited by substantial variability in pharmacokinetics, onset of adverse metabolic effects that include sustained lipid elevations and insulin resistance, and increased risk of lipodystrophy. Additionally, poor adherence to the often complex regimens can lead to emergence of PI-resistant human immunodeficiency virus (HIV) variants and treatment failure. Boosting blood levels of current PIs through coadministration of ritonavir can improve the pharmacokinetic characteristics of these agents, increasing the chances of success, but often at the price of additional adverse effects. New PIs in development have the potential to overcome at least some of these obstacles. Tipranavir, mozenavir, and atazanavir have favorable and unique resistance profiles, making them potentially effective in new treatment strategies in both PI-naïve and PI-experienced patients. Atazanavir does not cause the lipid elevations seen with current PIs, and it may improve adherence through once-daily dosing.Keywords
This publication has 41 references indexed in Scilit:
- British HIV Association (BHIVA) guidelines for the treatment of HIV‐infected adults with antiretroviral therapyHIV Medicine, 2001
- Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)JAMA, 2001
- Disorders of Glucose Metabolism in Patients Infected with Human Immunodeficiency VirusClinical Infectious Diseases, 2000
- Preliminary Guidelines for the Evaluation and Management of Dyslipidemia in Adults Infected with Human Immunodeficiency Virus and Receiving Antiretroviral Therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus GroupClinical Infectious Diseases, 2000
- HIV-1 Protease Inhibitors Induce an Increase of Triglyceride Level in HIV-Infected Men Without Modification of Insulin Sensitivity: A Longitudinal StudyHormone and Metabolic Research, 2000
- Outcome of a Second-Line Protease Inhibitor–Containing Regimen in Patients Failing or Intolerant of a First Highly Active Antiretroviral TherapyJAIDS Journal of Acquired Immune Deficiency Syndromes, 2000
- Reversal of Hyperlipidemia and Lipodystrophy in Patients Switching Therapy to NelfinavirJAIDS Journal of Acquired Immune Deficiency Syndromes, 2000
- Hyperlipidemia and Insulin Resistance Are Induced by Protease Inhibitors Independent of Changes in Body Composition in Patients With HIV InfectionJAIDS Journal of Acquired Immune Deficiency Syndromes, 2000
- Increasing morbidity from myocardial infarction during HIV protease inhibitor treatment?AIDS, 1999
- Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistanceThe Lancet, 1998