HIV-Infection: The Role of Insulin Resistance and Alternative Treatments

The impact of antiretroviral therapy (ART) on the natural history of HIV is indisputable, resulting in dramatic reductions in morbidity and mortality and improvements in quality of life. This recognition coincides with a change in view of HIV infection from a progressive fatal disease to a medically manageable chronic condition. However, the requirement for life-long therapy with ART has been associated with long-term metabolic toxicities (hyperlipidemia, insulin resistance, diabetes, and osteoporosis) and iatrogenic dysmorphias, termed lipodystrophy, that have increased the complexity of managing people living with HIV infection (PLWH), the manifestations of which include peripheral fat loss and central fat accumulation. Lipodystrophy has emerged as one of the most feared complications of ART for PLWH. The highly stigmatizing nature of this adverse event has been associated with feelings of low self-esteem, forced disclosure of HIV-status, and negative effect on antiretroviral adherence. Of more recent significant concern is the finding that the metabolic consequences of lipodystrophy and ART, as well as the inflammation caused by the virus, are strong mediators for the development of cardiovascular disease (CVD), diabetes, metabolic abnormalities, and fatty liver disease and will have important implications for the future health and survival of the PLWH. One of the possible mechanisms contributing to these metabolic abnormalities is insulin resistance (IR) that has been increasingly seen in PLWH. Interventions aimed at improving insulin sensitivity have been shown effective in alleviating some but not all of ART and/or HIV associated adverse outcomes. This chapter will review the evidence for IR as a potential mechanism involved in HIV-related complications and the role of alternative treatments in improving IR in people living with HIV infection.