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

Prins, Jan M.a*; Jurriaans, Suzannec*; van Praag, Rieneke M.E.a; Blaak, Hettye; van Rij, Ronalde; Schellekens, Peter Th.A.b; ten Berge, Ineke J.M.b; Yong, Si-Lab; Fox, Cecil H.f; Roos, Marijke T.L.e; de Wolf, Frankc; Goudsmit, Jaapc; Schuitemaker, Hannekee; Lange, Joep M.A.ad

Clinical: Original Papers

Background: A stable reservoir of latently infected, resting CD4 T cells has been demonstrated in HIV-1-infected patients despite prolonged antiretroviral treatment. This is a major barrier for the eradication of HIV by antiretroviral agents alone. Activation of these cells in the presence of antiretroviral 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 recombinant human IL-2 (days 2-6).

Results: The side-effects were fever, headache, nausea, diarrhea, and in one 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-1 RNA levels remained below the detection limit, but HIV-1 RNA levels in the lymph nodes increased two- to threefold. All patients developed antibodies against OKT3.

Conclusion: OKT3/IL-2 resulted in T cell activation and proliferation, and could stimulate HIV replication in patients having achieved prolonged suppression of plasma viremia. OKT3/IL-2 therapy was toxic and rapidly induced antibodies against OKT3.

From the aDepartment of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, and bDivision of Clinical Immunology and Rheumatology, cDepartment of Human Retrovirology, dNational AIDS Therapy Evaluation Centre (NATEC), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; eDepartment of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, the Netherlands; and fMolecular Histology Labs Inc., Gaithersburg, MD, USA.

*The first two authors contributed equally to this study.

Correspondence to: Jan M. Prins, Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Room F4-217, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Tel: +31 205664479; fax: +31 206972286; e-mail: j.m.prins@amc.uva.nl

Received: 18 May 1999; revised: 11 August 1999; accepted: 15 September 1999.

© 1999 Lippincott Williams & Wilkins, Inc.