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 low viral loads and clinical stability, but have been limited by their inability to eradicate virus in infected individuals, resulting in the need for indefinite therapy. The inability of antiretroviral drug therapy to eliminate 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 enhancement of host immunity. Proinflammatory cytokines are the central mediators of both innate and adaptive immunity, and modulation of these cytokines has been shown to alter anti-HIV-1 reactivity in vitro. Modulation of proinflammatory cytokines could therefore be utilized in strategies for immunotherapy of HIV-1 infection. The ultimate goal is to find regimens that could more durably suppress viral replication and potentially eliminate the need for indefinite antiretroviral therapy. This review presents 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.