Metabolisches Syndrom und Hyperlipidämie bei HIV-positiven Patienten

Zusammenfassung

Die Beeinflussung des Fett- und Glucosestoffwechsels sowie der Körperfettverteilung ist eine häufige unerwünschte Nebenwirkung der Behandlung der HIV-Infektion. Viele Patienten entwickeln während der antiretroviralen Therapie zentrale Kriterien des sog. metabolischen Syndroms wie Insulinresistenz, Dyslipidämie und zentrale Adipositas. Für die Patienten steht die Angst vor physischen Veränderungen durch fazialen Fettverlust im Vordergrund, da diese das Aussehen, das Gefühlsleben und die Lebensqualität belasten. Hinzu kommt die Furcht, die Arzt und Patient teilen: ein erhöhtes kardiovaskuläres Risiko der HIV-Infizierten durch die Therapie. Obwohl neuere Medikamente ein besseres Nebenwirkungsprofil aufweisen, müssen künftig weitere Medikamente entwickelt werden, um die HIV-Infektion effektiv zu behandeln und Langzeitkomplikationen zu ver hindern. Bis dahin gilt es, durch geschickten Einsatz der verfügbaren antiretroviralen Medikamente unerwünschte Nebenwirkungen zu verhindern oder zu verzögern und kardiovaskuläre Risiken zu verringern. Dazu kommen generelle Empfehlungen (Nikotinentwöhnung, körperliche Betätigung), der Wechsel der antiretroviralen Therapie (z. B. Austausch von bestimmten Proteaseinhibitoren) sowie die Therapie mit metabolisch wirksamen Medikamenten zur Senkung der Lipide und Insulinresistenz.

Abstract

The HIV lipodystrophy syndrome, a condition characterized by subcutaneous fat loss sometimes associated with relative or absolute accumulation of central fat, has a high prevalence in the treatment of HIV infection. Associated metabolic alterations include peripheral and hepatic insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertriglyceridemia, hypercholesterolemia, increased free fatty acids, and decreased HDL. Often, these metabolic abnormalities appear or deteriorate before the manifestation of fat redistribution. Hypertriglyceridemia is the leading lipid abnormality after initiation of HIV therapy frequently observed together with low HDL cholesterol. Raised levels of tissue plasminogen activator and plasminogen activator inhibitor-1 have been found in these patients, and there are reports about hypertension associated with antiretroviral therapy. Thus, the lipodystrophy syndrome in HIV therapy resembles a clinical situation that is known as the “metabolic syndrome” in HIV-negative patients. There is now good evidence that the metabolic abnormalities of HIV-infected patients harbor a significant risk for cardiovascular disease with as yet unknown consequences. In addition, several studies report a reduced quality of life in patients with body habitus changes leading to reduced therapy adherence. Current data indicate a rather multifactorial pathogenesis where HIV infection, its therapy, and patient-related factors are major contributors. Therapeutic and preventive strategies have, so far, been of only limited or no success. For reduction of the cardiovascular risk, recommendations proposed for non-HIV-infected patients like the National Cholesterol Education Program (NECP) have been adapted for HIV-infected patients. These should be regarded as rather preliminary and need to be evaluated in further clinical trials. General recommendations include dietary changes and physical activity, switch of antiretroviral drugs (replacement of protease inhibitors), and, finally, use of metabolically active drugs. Lipid-lowering agents can be considered for the treatment of severe hypertriglyceridemia, elevated LDL, or a combination of both. Some HMG-CoA reductase inhibitors, however, share common hepatic metabolization pathways with protease inhibitors (cytochrome P450 3A4 system), thereby potentially leading to additional liver and muscle toxicity. Although clinicians should assess cardiovascular risk factors and target risk reduction in HIV-infected patients, the primary goal in HIV therapy remains to be the effective suppression of viral replication leading to reduced morbidity and mortality.