Early immunologic failure is associatedwith early mortality among advanced hiv-infected adults initiating antiretroviral therapywith active tuberculosis

Abstract

Background. The relationship between antiretroviral therapy (ART) response and early mortality after ART initiation is unknown. We hypothesized that early mortality is associated with decreased early immunologic response to ART. Methods. We prospectively determined the association between changes in plasma human immunodeficiency virus type 1 (HIV-1) RNA and CD4+ T-cell counts (CD4 count) after 4 weeks of ART and early mortality in adults with pulmonary tuberculosis and pre-ART CD4 counts ≤125 cells/μL. Purified protein derivative (PPD)-specific immune recovery was determined by interferon-γ enzyme-linked immunosorbent spot assays. Levels of interleukin 6, C-reactive protein, and soluble CD14 were assessed. Patients with CD4 count and viral load values at baseline and week 4 were analyzed using multiple logistic regression. Results. Early immunologic response, but not pre-ART CD4 counts or virologic response, was related to early mortality (8 [interquartile range {IQR}, -18 to 43] vs 68 [IQR, 24-131] cells/μL, P = .002). In a logistic regression model, every 20 cells/μL increase in the CD4 count from baseline to week 4 was independently associated with a 40% reduction in the odds of death (odds ratio, 0.59 [95% confidence interval, .41-.87]). PPD-specific immune recovery was lower, whereas levels of immune activation were higher, among deaths. Conclusions. Early immunologic failure despite virologic suppression is associated with early mortality after ART initiation in advanced HIV/tuberculosis. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.