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

Ashwin Balagopal, David 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

17 Scopus citations


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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T-cell activation may identify patients with CD4<sup>+</sup> 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
Issue number2
StatePublished - Oct 1 2015


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

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)


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