Atherosclerotic vascular disease in HIV: it is not just antiretroviral therapy that hurts the heart!

Abstract

Although potent combination antiretroviral therapy has heralded an unparalleled improvement in the treatment of HIV-1-infected patients, the now well known metabolic complications of treatment, which include dyslipidemia, insulin resistance and changes in body fat distribution, are thought to contribute to an increased risk of atherosclerotic (cardio)vascular disease. Atherogenic changes in plasma lipids as well as some evidence of increased atherogenesis, however, had already been described in HIV-1-infected patients prior to the availability of combination antiretroviral therapy and even prior to that of suboptimal antiretroviral therapy. In this review, we will summarize the various possible factors and mechanisms involved in atherogenesis in HIV-1-infected individuals, with a focus on those mechanisms related to the infection itself and its immunological consequences. Recent data suggest that a treatment strategy involving repeated cycles of CD4-cell-guided combination antiretroviral therapy interruption is associated with a higher risk of (cardio)vascular disease than continuous treatment aimed at optimal viral suppression. Apart from the effects of combination antiretroviral therapy-associated metabolic derangements, HIV-1 infection, directly or indirectly, for instance by being associated with a state of chronic immune activation, may contribute to atherogenesis.