Antiretroviral Therapy in the Elite Controller: Justified or Premature?

(See the major article by Crowell et al on pages 1692–702.) Investigating the immune system of human immunodeficiency virus (HIV) elite controllers, or HIV-infected individuals who maintain undetectable plasma HIV RNA levels without antiretroviral therapy (ART), has led to advances in our understanding of HIV pathogenesis [1] and may be critical to the development of a functional cure for HIV infection [2, 3]. However, although other studies have shown that elite controllers maintain immune control of their viral replication, preventing disease progression in some, these individuals have higher levels of immune activation and chronic inflammation than HIV-infected persons with viral suppression during ART [4–7]. Whether or not elevated markers of inflammation in elite controllers are clinically meaningful is relevant to the question of whether elite controllers should be treated with ART. Elite controllers have also demonstrated higher levels of atherosclerosis than chronically HIV-1–infected persons receiving ART with undetectable HIV loads and HIV negative controls [5, 8]. The Strategies for Management of Anti-Retroviral Therapy (SMART) trial very clearly highlighted the association between chronic inflammation, observed in suppressed HIV-infected subjects receiving ART, and excess morbidity and mortality; subjects with elevated levels of the inflammatory markers interleukin 6 and D-dimer had higher all-cause mortality [9] and serious non-AIDS events, such as cardiovascular disease (CVD) [10, 11], than similarly suppressed subjects with lower inflammatory markers.