Trial Information

Effect of Recombinant Human Soluble Tumor Necrosis Factor Receptor (TNFR:Fc) on Interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-alpha) and Markers of Immune Activation in HIV-Infected Subjects

Both Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-alpha) are substances
naturally produced by the body's immune system. Evidence suggests that TNF-alpha production
may be excessive or inappropriate in HIV-infected patients. Elevated TNF-alpha levels can
result in increased IL-6 production and possibly increased HIV replication. TNFR:Fc is a
modification of a natural substance that binds to TNF-alpha and neutralizes its activity.
It is postulated that TNFR:Fc may result in decreased activity of TNF-alpha and lower IL-6
levels. HIV-infected patients who receive Interleukin-2 (IL-2) have been shown to have
higher TNF-alpha and IL-6 levels than those who do not receive IL-2. It is thought that
these higher levels of TNF-alpha and IL-6 may contribute to some of the flu-like symptoms
experienced by patients receiving IL-2. By decreasing the amount of IL-6 in the body and by
decreasing the action of TNF-alpha in the body, TNFR:Fc may have a role in the treatment of
HIV disease or in alleviating some of the symptoms related to IL-2 administration.

Six patients from each of the 3 treatment arms of ACTG 328 (HAART alone, HAART plus
intravenous (IV) rhIL-2, and HAART plus subcutaneous (SC) rhIL-2) who are about to be
randomized to Step II of ACTG 328 may participate in this prospective, nested substudy.
Patients randomized to the Interleukin-2 (IL-2) arms of ACTG 328 are pretreated with TNFR:Fc
(administered by infusion over 30 minutes) at week 16 of ACTG 928 (Course 3, Week 28 of ACTG
328), just prior to initiation of IL-2. Those randomized to the highly active antiretroviral
therapy (HAART) only arm of ACTG 328 receive treatment with TNFR:Fc at Week 16 of ACTG 928
(Week 28 of ACTG 328).