Tumor necrosis factor (TNF) system levels in human immunodeficiency virus-infected patients during highly active antiretroviral therapy: Persistent TNF activation is associated with virologic and immunologic treatment failure

Because persistent tumor necrosis factor (TNF)-alpha activation may play a pathogenic role in human immunodeficiency virus infection, TNF component le vels were assessed over 78 weeks in plasma and peripheral blood mononuclear cells (PBMC) during highly active antiretroviral therapy (HAART) in 40 HIV -infected patients. HAART induced a significant decline in plasma levels of TNF-alpha and soluble TNF receptors and was associated with a fall in the abnormally increased unstimulated and a rise in the abnormally low Mycobact erium avium complex-purified-protein derivative-stimulated TNF-alpha releas ed from PBMC, However, concentrations of these TNF components were not norm alized. Patients with virologic and immunologic treatment failure after 52 weeks had higher levels of several TNF components than other patients early after initiation of therapy, also during periods with adequate virologic r esponse. Although TNF components significantly decreased during HAART, thes e results support data indicating that full immunologic normalization is no t achieved during such therapy. The persistent activation of the TNF system in a subgroup of persons may be involved in treatment failure.