AEGiS-Glasgow [PL10.2] Hepatic adverse events (with and without coinfection)

Seventh International Congress on Drug Therapy in HIV Infection

Glasgow, UK - 14-17 November 2004

[PL10.2] Hepatic adverse events (with and without coinfection)

Int Cong Drug Therapy HIV 2004 Nov 14-18;7:Abstract No. PL10.2

Jürgen Rockstroh
Department of Medicine I, University of Bonn, Bonn, Germany

Meanwhile the benefits of highly active antiretroviral therapy (HAART) with regard to both survival and quality of life have been demonstrated beyond any doubts. Yet, HAART-associated toxicity has evolved as the main reason to discontinue or modify antiretroviral therapy. Hepatotoxicity appears to be of particular importance in this context as it can occur with nearly any antiretroviral regimen currently in use (see table). Most remarkably, longitudinal surveys have not only reported an increased incidence of hepatic injury in HAART-treated patients (especially in the hepatitis coinfected patient) but also identified life-threatening hepatotoxic events and end-stage liver disease in patients on antiretroviral treatment. Since rational alternatives to HAART are currently not available to control HIV infection, understanding the pathophysiology as well as a profound knowledge how to prevent and to treat HAART-related liver damage will be a continuous challenge for the present and future generations of hepatologists and HIV-physicians.

Drug	Typical time of occurrence	Laboratory findings (apart from elevated liver enzymes)	Histological hallmarks	Presumed mechanism of toxicity
NRTIs	More than 6 months after treatment initiation	Lactate acidosis, LDH elevation, amylase/lipase elevaton	Microvesicular steatosis of hepatocytes and giant mitochondria	Mitochondrial damage Inibition of cellular respiration
Nevirapine	1) during the initial 4 weeks	Eosinophilia, elevated WBC count, elevated IgE-levels	No conclusive data	Hypersensitivity reaction
	2) Gradually increasing over time with drug exposure	Elevated drug dosage	No conclusive data	Drug overdosage
Protease Inhibitors	Gradually increasing over time with drug exposure	Hyperlipidemia ?	Balooning degeneration of hepatocytes, Kupffer cell activation, pericellular fibrosis in zone 3	No data

SESSION 10: HEPATITIS CO-INFECTIONS AND ADVERSE EVENTS II
2004-11-14
PL10.2

Copyright © 2004 - Thomson ACUMED® All rights reserved. Thomson ACUMED® is an intelligent and innovative medical marketing and communications agency – a new division of The Gardiner-Caldwell Group Ltd, part of The Thomson Corporation, located in Tytherington, UK.

Reproduction of this abstract (other than one copy for personal reference) must be cleared through the authors.