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- Title
Early immunologic failure is associated with early mortality among advanced HIV-infected adults initiating antiretroviral therapy with active tuberculosis.
- Authors
Ravimohan, Shruthi; Tamuhla, Neo; Steenhoff, Andrew P; Letlhogile, Rona; Makutu, Didimalang Kgomotso; Nfanyana, Kebatshabile; Rantleru, Tumelo; Tierney, Ann; Nkakana, Kelebogile; Schwartz, Adam B; Gross, Robert; Macgregor, Rob Roy; Bellamy, Scarlett L; Frank, Ian; Weissman, Drew; Bisson, Gregory P
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Early immunologic failure despite virologic suppression is associated with early mortality after ART initiation in advanced HIV/tuberculosis.
- Publication
Journal of Infectious Diseases, 2013, Vol 208, Issue 11, p1784
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jit368