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 (rhulL)-10 on plasma HIV RNA levels and CD4 T-cell counts, and to evaluate its safety and tolerability in HIV-infected subjects. Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Subjects: Thirty-nine HIV-infected subjects with CD4 T-cell counts > 200 x 10(6)/l, plasma HIV RNA concentrations greater than or equal to 3.18 log(10) copies/ml and on stable antiretroviral therapy were recruited from six centers. Intervention: Subjects received (subcutaneously) rhulL-10 1 mug/kg daily, 4 mug/kg daily, 8 mug/kg three times per week, placebo daily or placebo three times per week for 4 weeks. Main outcome measures: 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. RhulL-10 was generally well tolerated. Two patients receiving rhulL-10 4 mug/kg required discontinuation due to thrombocytopenia. One patient receiving rhulL-10 4 mug/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. Conclusion: The lack of a demonstrable virological benefit, as assessed by plasma viral load, with 4 weeks of rhulL-10 does not support the development of this immune-based therapy for treatment of HIV infection. (C) 2000 Lippincott Williams & Wilkins.