The Role of Human Immunodeficiency Virus Type 1 (HIV-1) Proteins and Antiretroviral Drug Therapy in HIV-1-Induced Oxidative Stress

Abstract

Over 33 million people worldwide are infected with human immunodeficiency virus type 1 (HIV-1). In addition, over 2.7 million new cases are diagnosed each year with half of these infections occurring in individuals younger than 25 years (UNAIDS, 2008). Fortunately, since the emergence of highly active antiretroviral therapy (HAART) in 1996, morbidity and mortality associated with HIV-1 infection have been markedly decreased. HIV-1 infected patients have demonstrated dramatic decreases in viral burden and opportunistic infections, and an overall increase in life expectancy. Despite the positive HAART-associations outcomes, including the improvement of the clinical course, prognosis, and survival of patients infected with HIV-1, it has become increasingly clear that HIV-1 infected patients have an enhanced risk for developing noninfectious consequences of HIV-1 infection over time. In the last few years, lipodystrophy, characterized by redistribution of body fat, and insulin resistance, have been reported in many HIV-1 infected patients, and their relationship with antiretroviral drugs and HIV-1 infection per se have become a subject of debate and researches worldwide. Evidence suggests that HIV-1 infected patients are under chronic oxidative stress that may be involved in the development and progression of the disease. Oxidative stress is enhanced by the chronic inflammation that is associated with activation of lymphocytes and phagocytes, and is accompanied by the direct or indirect effects of several opportunistic pathogens. In addition, HIV-1 proteins and various components of current HAART regimes contribute to oxidative stress-induced disturbances such as cardiovascular disease (including metabolic syndrome and endothelial dysfunction), neurological disorders (HIV-1 dementia), and ocular complications (retinopathy). Cardiovascular complications are been recognized with increasing frequency and are associated with the greatest risk of death in HIV-1 patients. Studies demonstrated that not only do various components of HAART contribute to endothelial cell damage and vascular dysfunction in patients, but also the viral proteins themselves increase cardiovascular risk. HIV-1-associated cardiovascular disease progression is thus most likely a multifactorial process, resulting from a combination of distinct HIV-1 proteins as well as various components of current multidrug antiretroviral therapy (Kline et al., 2008).