The Pathology Induced by Highly Active Antiretroviral Therapy Against Human Immunodeficiency Virus: an Update

Abstract

The use of highly active antiretroviral therapy (HAART) has considerably improved the quality of life and has increased the survival of HIV-infected individuals. Although HAART can successfully suppress viral replication in the long term, it is not without significant toxicity, which can seriously compromise treatment effectiveness. Moreover, the rapid rate of virus mutation and subsequent emergence of drug-resistant HIV variants threaten the longer-term efficacy of HIV treatment. The most common adverse effects caused by HAART include a metabolic syndrome with lipodystrophy, hyperlipidemia and insulin resistance, deterioration in the clinical status due to various exaggerated local and systemic inflammatory reactions during the immunerestoration disease, and various hepatic, peripheral and cardiac muscle, kidney, bone, bone marrow, retinal, ear, and skin toxicities. The heterogeneity in the organs affected by the different drugs and the morphological features observed in tissues in HAART-treated patients raise possible explanations including differential distribution or activation of these agents. Antiretroviral drugs from new classes, as well as new drugs from existing classes with favorable resistance and side effect profiles are in various stages of development. However, new tissue disorders will be certainly described in the future in patients treated with these drugs. The different pathophysiology of the main adverse effects and the less common known side effects of antiretroviral therapy against HIV are described here, with special emphasis on the histological features induced by HAART.