Antiretroviral treatment interruptions and risk of non-opportunistic diseases

Abstract

Structured treatment interruptions have been studied as a strategy to reduce antiretroviral toxicities and expenditures in the treatment of HIV-infected individuals. Paradoxically, in addition to the increased incidence of death and opportunistic infections, these interruptions in therapy have resulted in the development of a number of non-opportunistic diseases, including cardiovascular events, renal insufficiency, hepatic failure, and non-AIDS-defining malignancies. Hypotheses regarding these findings suggest that the augmented stimulation of the host response to unabated viral replication may contribute to these comorbidities. Increased expression of chemokine receptor 5 and proinflammatory cytokines, disruption of immune cell function, and reduction in key inflammatory cells have been studied as potential mechanisms. Additionally, the increased inflammatory response has been shown to increase intracellular levels of nucleoside and nucleotide reverse transcriptase inhibitors, resulting in increased toxic manifestations. Structured treatment interruptions should be avoided in the management of HIV-infected individuals.