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

Abstract

Because persistent tumor necrosis factor (TNF)-alpha activation may play a pathogenic role in human immunodeficiency virus infection, TNF component levels 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 Mycobacterium avium complex-purified-protein derivative-stimulated TNF-alpha released from PBMC. However, concentrations of these TNF components were not normalized. 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 response. Although TNF components significantly decreased during HAART, these results support data indicating that full immunologic normalization is not achieved during such therapy. The persistent activation of the TNF system in a subgroup of persons may be involved in treatment failure.

Dengue Infection in a Human Immunodeficiency Virus-1 Positive Patient Chronically Infected with Hepatitis B Virus in Western Mexico

“…19 Even though the effect of HAART treatment during dengue infection remains unknown, the attenuation of certain cytokines in HIV-1-infected patients treated with HAART, such as IL-10 and TNF-α, could play an important role in decreasing dengue disease progression in HIV-1-positive patients. 20,21 Both IL-10 and TNF-α are strongly associated with severe dengue infection. 22 The HIV-1 viral loads in our patient remained at normal levels (< 40 HIV-1 RNA copies/mL) during DENV-1 infection and 6 months later.…”

HIV Type 1 Infection Up-Regulates TLR2 and TLR4 Expression and Function in Vivo and in Vitro

“…However, in the case of HIV-1 infection, innate immune activation also drives HIV-1 replication via signaling pathways downstream of the TLRs. 40 While some studies have explored how different types of cells from HIV-1-infected patients respond to TLR agonists (effect on expression and its functionality), the ultimate aim of this study was to determine the effect on TLR2 and TLR4 expression and functionality in PBMCs and MDMs derived from healthy subjects and in vitro infected with HIV-1 and then treated with agonist for the two TLRs. The altered expression of both TLRs in antigen-presenting cells from HIV-1-infected patients was also evaluated.…”

Bone mass and mineral metabolism in HIV+ postmenopausal women

“…Estrogen down-regulates many of the proinflammatory cytokines (TNF-α, IL-1, Il-6) that increase bone resorption [2,32]. These proinflammatory cytokines have all been found to be elevated in HIV+ individuals [1,4] and may not be completely suppressed after ART [33,34]. Receptor activator of nuclear factor kappa-B (RANK), its ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) are three recently identified members of the TNF ligand and receptor-signaling family that are the final effectors of bone resorption [35,36].…”