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Title: Pre-cART elevation of CRP and CD4<sup>+</sup>t-cell immune activation associated with HIV clinical progression in a multinational case-cohort study
Authors: Ashwin Balagopal
David M. Asmuth
Wei Teng Yang
Thomas B. Campbell
Nikhil Gupte
Laura Smeaton
Cecilia Kanyama
Beatriz Grinsztejn
Breno Santos
Khuanchai Supparatpinyo
Sharlaa Badal-Faesen
Javier R. Lama
Umesh G. Lalloo
Fatima Zulu
Jyoti S. Pawar
Cynthia Riviere
Nagalingeswaran Kumarasamy
James Hakim
Xiao Dong Li
Richard B. Pollard
Richard D. Semba
David L. Thomas
Robert C. Bollinger
Amita Gupta
Keywords: Medicine
Issue Date: 1-Oct-2015
Abstract: Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Background: Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore, some cART initiators are not fully benefitted by cART. Immune activation precART may predict clinical progression in cART initiators. Methods: A case-cohort study (n = 470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings clinical trial (1571 HIV treatment-naive adults who initiated cART; CD4+T-cell count ,300 cells/mm3; 9 countries) was conducted. A subcohort of 30 participants per country was randomly selected; additional cases were added from the main cohort. Cases [n = 236 (random subcohort 36; main cohort 200)] had clinical progression (incident WHO stage 3/4 event or death) within 96 weeks after cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Results: Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4+T-cell count was 167 cells per cubic millimeter. In multivariate analysis, highest quartile C-reactive protein concentration [adjusted hazard ratio (aHR), 2.53; 95% confidence interval (CI): 1.02 to 6.28] and CD4+ T-cell activation (aHR, 5.18; 95% CI: 1.09 to 24.47) were associated with primary outcomes, compared with lowest quartiles. sCD14 had a trend toward association with clinical failure (aHR, 2.24; 95% CI: 0.96 to 5.21). Conclusions: Measuring C-reactive protein and CD4+T-cell activation may identify patients with CD4+T-cell counts ,300 cells per cubic millimeter at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART.
ISSN: 10779450
Appears in Collections:CMUL: Journal Articles

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