Pre-cART elevation of CRP and CD4+ t-cell immune activation associated with HIV clinical progression in a multinational case-cohort study

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. PollardRichard D. Semba, David L. Thomas, Robert C. Bollinger, Amita Gupta

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)163-171
Number of pages9
JournalJournal of acquired immune deficiency syndromes
Volume70
Issue number2
DOIs
StatePublished - Oct 1 2015

Keywords

  • C-reactive protein
  • Global HIV
  • Immune activation
  • T-cell activation
  • cART clinical outcomes

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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