Pretreatment levels of soluble cellular receptors and interleukin-6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy.

TitlePretreatment levels of soluble cellular receptors and interleukin-6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2010
AuthorsKalayjian RC, Machekano RN, Rizk N, Robbins GK, Gandhi RT, Rodriguez BA, Pollard RB, Lederman MM, Landay A
JournalJ Infect Dis
Volume201
Issue12
Pagination1796-805
Date Published2010 Jun 15
ISSN1537-6613
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Biomarkers, Case-Control Studies, CD4 Lymphocyte Count, CD8-Positive T-Lymphocytes, Disease Progression, Female, HIV Infections, Humans, Interleukin-6, Male, Middle Aged, Receptors, Tumor Necrosis Factor, Viral Load
Abstract

BACKGROUND: To identify inflammatory pathways that may contribute to the pathogenesis of human immunodeficiency virus (HIV) disease, we explored associations between AIDS or death and different inflammatory markers, including selected soluble tumor necrosis factor superfamily receptors (sTNFRs) and ligands, interleukin (IL)-6, and CD8 T cell activation, in individuals treated with highly active antiretroviral therapy (HAART).

METHODS: A case-control study of subjects in AIDS Clinical Trials Group (ACTG) protocols 384 and 5015, who were matched according to the CD4 cell count and plasma viral load at baseline, was performed using conditional logistic regression.

RESULTS: Higher pretreatment concentrations of sTNFR-1, sCD27, sCD40L, and plasma IL-6 were associated with a new AIDS-defining illness or death in separate models adjusted for age, sex, hemoglobin, and the latest CD4 cell counts. In additional models that excluded case patients with opportunistic infections, sTNFR-1, sCD27, and sCD40L were each associated with a new AIDS-defining malignancy or death that developed at a median of 51 weeks after initiation of HAART, by which time the majority of subjects had a CD4 cell count of >200 cells/cm(3) and had achieved a plasma viral load of <50 copies/mL.

CONCLUSION: These data are compatible with a model in which these soluble inflammatory markers identify pathways that may contribute to the pathogenesis of HIV disease progression, pathways that might not be a direct consequence of ongoing HIV type 1 replication.

DOI10.1086/652750
Alternate JournalJ. Infect. Dis.
PubMed ID20446847
PubMed Central IDPMC2873127
Grant List5 RO1 AI066992-04 / AI / NIAID NIH HHS / United States
AI 36219 / AI / NIAID NIH HHS / United States
AI 68636 / AI / NIAID NIH HHS / United States
AI U01 68635 / AI / NIAID NIH HHS / United States
AI062435 / AI / NIAID NIH HHS / United States
AI069472 / AI / NIAID NIH HHS / United States
AI69501 / AI / NIAID NIH HHS / United States
M01 RR000080-411056 / RR / NCRR NIH HHS / United States