Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults: a case-control study

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BMC Medicine


Various individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarkers to identify biomarker groupings (factors) and determine their association with HIV clinical treatment failure (CTF) and incident active tuberculosis (TB).


Within a multicountry randomized trial of antiretroviral therapy (ART) efficacy (PEARLS) among HIV-infected adults, we nested a case-control study (n = 290; 124 cases, 166 controls) to identify underlying factors, based on EFA of 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status. The EFA biomarker groupings results were used in Cox proportional hazards models to study the association with CTF (primary analysis where cases were incident World Health Organization stage 3, 4 or death by 96 weeks of ART) or incident active TB (secondary analysis).


In the primary analysis, based on eigenvalues> 1 in the EFA, three factors were extracted: (1) carotenoids), (2) other nutrients, and (3) inflammation. In multivariable-adjusted models, there was an increased hazard of CTF (adjusted hazard ratio (aHR) 1.47, 95% confidence interval (CI)1.17-1.84) per unit increase of inflammation factor score. In the secondary incident active TB case-control analysis, higher scores of the high carotenoids and low interleukin-18 factor was protective against incident active TB (aHR 0.48, 95% CI 0.26-0.87).


Factors identified through EFA were associated with adverse outcomes in HIV-infected individuals. Strategies focused on reducing adverse HIV outcomes through therapeutic interventions that target the underlying factor (e.g., inflammation) rather than focusing on an individual observed biomarker might be more effective and warrant further investigation.

Shivakoti R, Gupte N, Tripathy S, Poongulali S, Kanyama C, Berendes S, Cardoso SW, Santos BR, La Rosa A, Mwelase N, Pillay S, Samaneka W, Riviere C, Sugandhavesa P, Bollinger RC, Balagopal A, Semba RD, Christian P, Campbell TB, Gupta A; NWCS 319 and PEARLS Study Team. Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults: a case-control study. BMC Med. 2018 Sep 24;16(1):161. doi: 10.1186/s12916-018-1150-3. PMID: 30244671.
  • National AIDS Research Institute, Pune, India.
  • YR Gaitonde Center for AIDS Research and Education, Chennai, India.
  • UNC Lilongwe, Lilongwe, Malawi.
  • Malawi College of Medicine-Johns Hopkins University Research Project, Blantyre, Malawi.
  • STD/AIDS Clinical Research Laboratory, Instituto de Pesquisa Clinica Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil.
  • Hospital Nossa Senhora de Conceiçã, Porto Alegre, Brazil.
  • Asociacion Civil Impacta Salud y Educacion, Lima, Peru.
  • Department of Medicine, University of Witwatersrand, Johannesburg, South Africa.
  • Durban International Clinical Research Site, Durban University of Technology, Durban, South Africa.
  • University of Zimbabwe Clinical Research Centre, Harare, Zimbabwe.
  • Les Centres GHESKIO, Port-Au-Prince, Haiti.
  • Research Institute for Health Sciences, Chiang Mai, Thailand.
  • Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Bill and Melinda Gates Foundation, Seattle, USA.
  • Department of Medicine, Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, CO, USA.