Inhibition of Immunoreactive Tumor Necrosis Factor- by a Chimeric Antibody in Patients Infected with Human Immunodeficiency Virus Type 1

Abstract

Tumor necrosis factor-α (TNF-α), a proinftammatory cytokine known to stimulate human immunodeficiency virus type 1 (HIV-1) replication, has been implicated in the pathogenesis of HIV-1 infection. Inhibition of TNF-α by a chimeric humanized monoclonal antibody, cA2, was investigated in 6 HIV-1-infected patients with CD4 cell counts 3. Two consecutive infusions of 10 mg/kg 14 days apart were well tolerated, and a prolonged serum half-life for cA2 (mean, 257 ± 70 h) was demonstrated. Serum immunoreactive TNF-α concentrations fell from a mean prestudy value of 6.4 pg/mL (range, 4.2–7.9) to 1.1 pg/mL (range, 0.5–2.2) 24 h after the first infusion and returned to baseline within 7–14 days. A similar response was seen after the second infusion. No consistent changes in CD4 cell counts or plasma HIV RNA levels were observed over 42 days. Future studies evaluating the therapeutic utility of long-term TNF-α suppression using anti-TNF-α antibodies are feasible and warranted.