Insulin resistance in treated HIV infection

Insulin resistance (IR) was one of the first metabolic complications reported with highly active antiretroviral therapy for HIV infection. It continues to be of concern despite the introduction of newer antiretrovirals with safer metabolic profiles and is associated with inflammation and the development of diabetes mellitus. As the HIV-infected population ages, the prevalence of IR is likely to rise. Specific antiretrovirals can increase insulin resistance through two principal mechanisms, either directly by interfering with insulin signalling at the cellular level or indirectly as a consequence of defects in lipid metabolism (lipotoxocity) arising from antiretroviral toxicities such as the IR observed in those with HIV-associated lipodystrophy. There is considerable overlap between different antiretrovirals in their propensity to cause IR making it more difficult to attribute development of IR to a particular antiretroviral medication. In addition, in the setting of a generalised epidemic of obesity that exists in many populations worldwide, HIV-infected patients may be more prone to the consequences of antiretroviral-induced insulin resistance and diabetes mellitus. Optimal screening and treatment strategies for IR in treated HIV infection have not been established. In this article we review current opinion on insulin resistance in HIV and identify potential areas for future research.