Proinflammatory Cytokines in HIV Disease – A Review and Rationale for New Therapeutic Approaches

Antiretroviral drugs currently in use for treating HIV-1 infection are very effective at maintaining lowviral loads and clinical stability, but have been limited by their inability to eradicate virus in infectedindividuals, resulting in the need for indefinite therapy. The inability of antiretroviral drug therapy toeliminate HIV-1 infection is thought to be due to incomplete restoration of host immunity to the virus.New strategies to improve control of HIV-1 infection during antiretroviral therapy should target enhancementof host immunity. Proinflammatory cytokines are the central mediators of both innate andadaptive immunity, and modulation of these cytokines has been shown to alter anti-HIV-1 reactivityin vitro. Modulation of proinflammatory cytokines could therefore be utilized in strategies for immunotherapyof HIV-1 infection. The ultimate goal is to find regimens that could more durably suppressviral replication and potentially eliminate the need for indefinite antiretroviral therapy. This reviewpresents what is known about the dysregulation of proinflammatory cytokines in HIV-1 infection,highlighting newly available immune-based therapies that could augment antiretroviral drug therapies.