Understanding and managing the adverse effects of antiretroviral therapy

Highly active antiretroviral therapy (HAART) has changed the landscape of HIV disease in a way that seemed unthinkable a decade ago; from an almost uniformly fatal disease to a chronic manageable one. The first HAART regimens worked in suppressing virus, but were encumbered by a variety of short term and long term side effects. More recent regimens became simpler, easier to take, and with fewer adverse events. As we look to people living perhaps a normal life span with HIV, the increasing number of antiretroviral agents available means that individualizing treatment has become more feasible and the longer downstream adverse events related to HAART, such as its effect on cardiovascular disease and diabetes, renal and hepatic disease, have begun to dominate our choice of drugs. A knowledge of both the short and long term adverse events associated with HAART is essential for providers and for patients. For new drugs to be acceptable in the current field, they will have to pass a litmus test of tolerability. Since adverse events are often remarkably idiosyncratic, pharmacogenomics may offer a way of predicting side effects and their severity from a particular drug or drug class in individual patients. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol. 85, issue 1, 2010.