INHIBITION OF IMMUNOREACTIVE TUMOR-NECROSIS-FACTOR-ALPHA BY A CHIMERIC ANTIBODY IN PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine kn own to stimulate human immunodeficiency virus type 1 (HIV-1) replicati on, has been implicated in the pathogenesis of HIV-1 infection. Inhibi tion of TNF-alpha by a chimeric humanized monoclonal antibody, cA2, wa s investigated in 6 HIV-1-infected patients with CD4 cell counts <200/ mm(3). Two consecutive infusions of 10 mg/kg 14 days apart were well t olerated, and a prolonged serum half-life for cA2 (mean, 257 +/- 70 h) was demonstrated. Serum immunoreactive TNF-alpha 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 baselin e within 7-14 days. A similar response was seen after the second infus ion. 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-alpha suppression using anti-TNF-alpha antib odies are feasible and warranted.