Adverse events of antiretroviral therapy: aspects of pathogenesis

Highly active antiretroviral therapy has resulted in remarkable reduction of morbidity and mortality of HIV infection. With increasing duration of therapy metabolic alterations such as hyperlipidemia diabetes mellitus type 2 and lipodystrophy are encountered which considerably reduced quality of life for the patients. These adverse events are most likely due to protease inhibitors and nucleoside analogues with synergistic effects. The pathogenesis is related to metabolical alterations of the adipocytes with cellular insulin resistance and enhanced apoptosis of these cells caused by adipocytic cytokines such as adiponectin,leptin, TNF-alpha and interleukin 2. Switch of therapy regimens with elimination of the most suspicious substances and certain protease inhibitors can lead to improvement of deranged metabolism. Also symptomatic therapy is possible to cope with hyperlipidemia and diabetes, although no effective treatment is available to reverse already existing lipodystrophy. Our knowledge about the pathogenesis of these alterations might lead to new concepts and causal therapy in the future.