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

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Journal of Acquired Immune Deficiency Syndromes

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; 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.

Balagopal A, Asmuth DM, Yang W-T, Campbell T, Gupte N, Smeaton L, Kanyama C, Grinsztejn B, Santos B, Supparatpinyo K, Badal-Faesen S, Lama JR, Lalloo U, Zulu F, Pawar JS, Riviere C, Kumarasamy N, Hakim J, Li X-D, Pollard RB, Semba RD, Thomas DL, Bollinger RC, Gupta A. Pre-cART elevation of CRP and CD4+ T-cell immune activation associated with HIV clinical progression in m Multinational case-cohort study. J Acquir Immune Def Syndr. 2015 Oct 1.
  • Department of Medicine, University of California Davis, Sacramento, CA
  • Department of Medicine, University of Colorado Denver, Aurora, CO
  • Harvard University Center for AIDS Research, Harvard School of Public Health, Boston, MA
  • University of North Carolina Project, Lilongwe, Malawi
  • Instituto de Pesquisa Clinica Evandro Chagas, Manguinhos, Brazil
  • Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil
  • Department of Medicine, Chiang Mai University, Chiang Mai, Thailand
  • Department of Medicine, University of Witwatersrand, Johannesburg, South Africa
  • IMPACTA PERU Clinical Trials Unit, Asociacion Civil Impacta Salud y Educacion, Lima, Peru
  • Department of Pulmonology, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa
  • Malawi College of Medicine-Johns Hopkins Research Project, Kachere Rehabilitation Centre, Blantyre, Malawi
  • National AIDS Research Institute, Pune, India
  • Les Centres GHESKIO, Port-au-Prince, Haïti
  • YR Gaitonde Center for AIDS Research and Education, Chennai, India
  • Department of Medicine, University of Zimbabwe, Harare, Zimbabwe