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

AIDS. 1999 Dec 3;13(17):2405-10. doi: 10.1097/00002030-199912030-00012.

Abstract

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.

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • DNA, Viral / blood
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / therapy*
  • HIV-1* / genetics
  • HIV-1* / isolation & purification
  • Humans
  • In Situ Hybridization
  • Interleukin-2 / administration & dosage*
  • Interleukin-2 / adverse effects
  • Lymph Nodes / immunology
  • Lymph Nodes / virology
  • Lymphocyte Activation / drug effects
  • Muromonab-CD3 / administration & dosage*
  • Muromonab-CD3 / adverse effects
  • Muromonab-CD3 / blood
  • RNA, Viral / blood
  • RNA, Viral / isolation & purification
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • Viremia / drug therapy
  • Viremia / immunology
  • Viremia / therapy
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • Interleukin-2
  • Muromonab-CD3
  • RNA, Viral
  • Recombinant Proteins