Immune-activation with anti-CD3 and recombinant human IL-2 in HIV-1-infected patients on potent antiretroviral therapy

Background: A stable reservoir of latently infected, resting CD4 T cells ha s been demonstrated in HIV-l-infected patients despite prolonged antiretrov iral treatment. This is a major barrier for the eradication of HIV by antir etroviral agents alone. Activation of these cells in the presence of antire troviral therapy might be a strategy to increase the turnover rate of this reservoir. Methods: Three HIV-1-positive patients on potent antiretroviral therapy, in whom plasma viremia had been suppressed to below 5 copies/ml for at least 26 weeks, were treated with a combination of OKT3 (days 1-5) and recombinan t human IL-2 (days 2-6). Results: The side-effects were fever, headache, nausea, diarrhea, and in on e of the patients transient renal Failure and seizures,The regimen resulted in profound T cell activation. In one patient plasma HIV-1 RNA transiently increased with a peak at 1500 copies/ml. In the other two patients plasma HIV-l RNA levels remained below the detection limit, but HIV-1 RNA levels i n the lymph nodes increased two- to threefold. All patients developed antib odies against OKT3. Conclusion: OKT3/IL-2 resulted in T cell activation and proliferation, and could stimulate HIV replication in patients having achieved prolonged suppr ession of plasma viremia. OKT3/IL-2 therapy was toxic and rapidly induced a ntibodies against OKT3. (C) 1999 Lippincott Williams & Wilkins.