Antiretroviral Therapy-associated Serious and Life-threatening Toxicities

Abstract

In the late 1980s and early 1990s, when HIV/AIDS had become the leading cause of death in 25- to 44-year-old persons in the United States, it was acceptable to prescribe newer antiretroviral therapy such as zidovudine, which has significant bone marrow toxicities but can potentially improve patient survival. Although current antiretroviral therapy is not likely to eradicate HIV-1 infection, the advances in the use of combination antiretroviral therapy (including protease inhibitors and non-nucleoside reverse transcriptase inhibitors) have dramatically improved the overall survival, immune status, and productivity of HIV-infected individuals in developed countries. Instead of prevention and treatment of HIV-associated complications, many of the patients" clinic visits are focused on finding strategies to manage and prevent antiretroviral therapy-associated complications. Because only a few HIV-infected persons fulfilling stringent inclusion criteria were included in premarketing clinical trials and because the US Food and Drug Administration"s (FDA) accelerated approval process for antiretroviral therapy requires only 24-week safety and efficacy data, newly emerging and previously unrecognized adverse effects of antiretroviral therapy continue to surface when these drugs are administered to a larger patient population for a longer duration. Unfortunately, some of these adverse effects can be unpredictable and serious, and, if not recognized early and managed aggressively, can lead to fatality. This article reviews four of the most serious, life-threatening toxicities associated with antiretroviral therapy.