Immuno-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 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.


CONCLUSIONS
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.
Prins
J M
JM
Department of Internal Medicine, Tropical Medicine, and AIDS, Academic Medical Center, University of Amsterdam, The Netherlands. j.m.prins@amc.uva.nl
Jurriaans
S
S
van Praag
R M
RM
Blaak
H
H
van Rij
R
R
Schellekens
P T
PT
ten Berge
I J
IJ
Yong
S L
SL
Fox
C H
CH
Roos
M T
MT
de Wolf
F
F
Goudsmit
J
J
Schuitemaker
H
H
Lange
J M
JM
D019380:Anti-HIV Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects; D016853:Muromonab-CD3 / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D004279:DNA, Viral; D007376:Interleukin-2; D016853:Muromonab-CD3; D012367:RNA, Viral; D011994:Recombinant Proteins