Pathogenesis of HIV infection: total CD4+ T-cell pool, immune activation, and inflammation.

Recent studies have yielded important findings on the pathogenesis of HIV infection. HIV infection leads to immune dysfunction through CD4+ T-cell depletion (immunodeficiency) and immune activation (immunosuppression). In vivo imaging studies of nonhuman primates indicate that the total body pool of CD4+ T cells may provide more accurate quantitation of immune depletion in HIV infection than the peripheral blood CD4+ count. Immune activation appears to be driven by both a homeostatic response to CD4+ cell depletion and an inflammatory response to HIV infection. The evidence is mounting that ongoing inflammation and coagulation account for the increased risk of serious nonopportunistic events in patients with HIV infection. Studies in long-term nonprogressors indicate that the HIV-specific immune responses in these patients are distinguished by clonal expansions of antigen-specific CD8+ T cells. Additional study of the precise mechanisms that allow immunologic control of infection in these patients may contribute to development of vaccines and immune-based therapies. This article summarizes a presentation made by H. Clifford Lane, MD, at the International AIDS Society-USA continuing medical education program held in May 2009 in Chicago. The original presentation is available as a Webcast at www.iasusa.org.