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Cessation of HAART Plus Daily Low-Dose Interleukin 2 to Promote Immunity to HIV K. A. SMITH*, E. L. JACOBSON, T. SOHN, D. WARREN, R. EMERT, M. GIORDANO, J. RUITENBERG, and C. A. WATERS. New York and San Jose, CA Discontinuation of Highly Active Anti-Retroviral Therapy (HAART) results in a rapid relapse of viremia, except when HIV is identified and treated early. Accordingly, in individuals infected chronically, HAART must be administered indefinitely, and protective immunity to HIV has not been considered possible. Most viral infections are combated by the proliferative expansion of antigen-selected lymphocytes, especially of the CD8+ T cell subset. This clonal expansion is CD4+ T cell-dependent, and interleukin 2 (IL2)-dependent. Therefore, to test a new strategy to promote immunity to HIV, 9 individuals chronically infected with HIV were selected on the basis that they had become aviremic, and had normal circulating lymphocyte concentrations on HAART plus daily, low dose IL2 therapy. Upon cessation of HAART, but continuation of IL2, plasma HIV became detectable in all individuals in 19 +/- 3 (SEM) days, then increased rapidly over 2 weeks (dbl time 2 +/- 0.2 days), to a peak of 348,123 +/- 232,811 HIV RNA molecules/ml. Remarkably, the virus concentration then decreased progressively over the next 4 weeks, reaching a low stable level of 26,086 +/- 8,087 HIV RNA molecules/ml, < 10% of the peak concentration (p <0.001). Moreover, this level was significantly lower than the mean viral load prior to HAART (70,315 +/- 20,459 HIV RNA molecules/ml, p <0.01). The only significant change in circulating CD4+ T cells occurred just after the peak of the viremia, when there was a 24% decrease, compared with baseline levels (p < 0.01), while NK cells did not change significantly during the entire interval. By comparison, coincident with the reappearance of viremia, CD8+ T cells increased progressively, eventually to ~200% of baseline levels (p < 0.01), and then remained at this elevated level while the plasma HIV declined progressively. Thus, contrary to previous assumptions, chronic HIV infection does not preclude the development of effective immune reactivity to HIV. Additional trials to test the strategy of the cessation of HAART, to permit endogenous HIV antigenic stimulation of IL2 responsiveness, combined with daily, low dose IL2 therapy to promote the expansion of antigen-activated CD8+ T cells, now appear warranted. Key Words: HAART Cessation, HIV Immunity, interleukin 2 |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |