Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case–Cohort Study. (1st October 2015)

• Record Type: Journal Article
• Authors: Balagopal, Ashwin; Asmuth, David M.; Yang, Wei-Teng; Campbell, Thomas B.; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R.; Lalloo, Umesh G.; Zulu, Fatima; Pawar, Jyoti S.; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B.; Semba, Richard D.; Thomas, David L.; Bollinger, Robert C.; Gupta, Amita
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 70:Number 2(2015)
• Publication Date: 2015-10-01
• Subjects: immune activation -- global HIV -- cART clinical outcomes -- C-reactive protein -- T-cell activation; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/QAI.0000000000000696
• Languages: English
• ISSNs: 1525-4135

Abstract

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 pre-cART 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/mm 3 ; 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. Abstract : Supplemental Digital Content is Available in the Text.