Metabolic complications associated with antiretroviral therapy

Mortality rates in the HIV-infected patient population have decreased with the advent of highly active antiretroviral therapy (HAART) for the treatment of AIDS. Due to the chronic nature of HAART, long-term metabolic complications are associated with therapy, such as hyperlipidemia, fat redistribution and diabetes mellitus. Currently, all of these symptoms are classified as the lipodystrophy (LD) syndrome(s). However, hyperlipidemia and fat redistribution occur independently, indicating there may be multiple syndromes associated with HAART. Although fat gain/loss and dyslipidemia occur in protease inhibitor (PI) naı̈ve patients treated with nucleoside reverse transcriptase inhibitors (NRTIs), combination therapies (PI and NRTI) accelerate the syndrome. Recent clinical trials, cell culture and animal studies indicate that these effects are not drug class specific and select PIs, NRTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) can be associated with metabolic complications. Moreover, the effects can vary between various members of the same class of antiretroviral agents (i.e. not all PIs cause the same adverse reactions) and may be influenced by duration of infection, genetics and environmental factors. Although HAART increases the risk of metabolic complications, this does not outweigh the benefits of survival. In this review, we summarize the latest clinical and scientific information on these metabolic complications, examine current hypotheses explaining the syndromes and comment on the existing methods available to manage these metabolic side effects.