Systemic Immune Activation and Microbial Translocation in Dual HIV/Tuberculosis-Infected Subjects

Abstract

BACKGROUND: Systemic immune activation is a strong predictor of progression of human immunodeficiency virus type 1 (HIV-1) disease and a prominent feature of infection with Mycobacterium tuberculosis. OBJECTIVE: To understand the role of systemic immune activation and microbial translocation in HIV/tuberculosis dually infected patients over the full spectrum of HIV-1 immunodeficiency, we studied circulating sCD14 and lipopolysaccharide (LPS) and their relationship to HIV-1 activity. METHODS: Two cohorts of HIV/tuberculosis subjects defined by CD4 T-cell count at time of diagnosis of tuberculosis were studied: those with low (<350/μL) and those with high (≥ 350/μL) CD4 T-cell count. Circulating soluble CD14 (sCD14) and LPS were assessed. RESULTS: Levels of sCD14 were higher in HIV/tuberculosis with high (≥ 350/μL) as compared to low CD4 T-cell count (P < .001). Whereas sCD14 levels remained elevated in HIV/tuberculosis subjects with lower CD4 T-cell counts despite treatment of tuberculosis, in HIV/tuberculosis patients with higher CD4 T-cell count (≥ 350/μL), levels declined regardless of whether highly active antiretroviral therapy (HAART) was included with the anti-tuberculosis regimen. Circulating LPS levels in HIV/tuberculosis patients with CD4 T-cell count ≥ 350/μL were unaffected by treatment of tuberculosis with or without HAART. CONCLUSION: During HIV/tuberculosis, systemic immune activation is dissociated from microbial translocation. Changes in circulating sCD14 and LPS are dependent on CD4 T-cell count.