A multicenter, randomized, double-blind, placebo-controlled trial of recombinant human interleukin-10 in HIV-infected subjects.
OBJECTIVE
To determine the effect of multiple subcutaneous doses of recombinant human interleukin (rhuIL)-10 on plasma HIV RNA levels and CD4 T-cell counts, and to evaluate its safety and tolerability in HIV-infected subjects.


METHODS
Prospective, randomized, double-blind, placebo-controlled, multicenter trial.


METHODS
Thirty-nine HIV-infected subjects with CD4 T-cell counts > 200 x 10(6)/l, plasma HIV RNA concentrations > or = 3.18 log10 copies/ml and on stable antiretroviral therapy were recruited from six centers.


METHODS
Subjects received (subcutaneously) rhuIL-10 1 microg/kg daily, 4 microg/kg daily, 8 microg/kg three times per week, placebo daily or placebo three times per week for 4 weeks.


METHODS
Prospectively defined outcomes included safety and tolerability, plasma HIV RNA levels and CD4 T-cell counts. Outcomes were assessed at baseline, weeks 1, 2, 3 and 4 during treatment and weeks 2 and 4 following completion of therapy.


RESULTS
Baseline characteristics were similar in all groups. Compared to baseline, no significant change in plasma HIV RNA concentrations or CD4 T-cell counts was observed in any of the groups. RhuIL-10 was generally well tolerated. Two patients receiving rhuIL-10 4 microg/kg required discontinuation due to thrombocytopenia. One patient receiving rhuIL-10 4 microg/kg who had chronic hepatitis B and C infections discontinued drug because of elevated liver function tests. One patient receiving placebo discontinued study drug because of depression.


CONCLUSIONS
The lack of a demonstrable virological benefit, as assessed by plasma viral load, with 4 weeks of rhuIL-10 does not support the development of this immune-based therapy for treatment of HIV infection.
Angel
J B
JB
The Ottawa Hospital Research Institute and Department of Medicine, University of Ottawa, Ontario, Canada.
Jacobson
M A
MA
Skolnik
P R
PR
Giordano
M
M
Shapiro
L
L
LeBeaut
A
A
Greaves
W
W
Fuchs
A C
AC
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use
D000998:Antiviral Agents; D012367:RNA, Viral; D011994:Recombinant Proteins; D016753:Interleukin-10