Significant Toxicities Associated with Antiretroviral Therapy

Use of at least three potent antiretroviral agents has become the standard of care in the management of HIV infection. The potential toxicities associated with highly active antiretroviral therapy (HAART) however, may limit a patient’s ability to adhere to and tolerate these agents. Although a comprehensive discussion of all toxicities associated with HAART is beyond the scope of this article, selected short-term and long-term significant toxicities will be reviewed. Short-term toxicities that will be discussed include abacavir-induced hypersensitivity reactions, efavirenz-associated central nervous system side effects and rash associated with the non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitor (PI) amprenavir. Several long-term toxicities associated with the nucleoside reverse transcriptase inhibitors (NRTIs) are hypothesized to be due to mitochondrial toxicity. These toxicities include myositis and lactic acidosis with hepatic steatosis, pancreatitis and peripheral neuropathy. Some experts also hypothesize that mitochondrial toxicity is responsible for the lipodystrophy syndrome, which includes hyperglycemia, abnormal fat redistribution and dyslipidemia. Finally, indinavir-associated nephrolithiasis, which may present with either short term or long term use will be discussed. This article will provide the practicing pharmacist with a review of these significant toxicities, the implicated agents, incidence, usual clinical presentation, and recommendations for management.