title: T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy.
abstract: OBJECTIVE
  To estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets.
  
  
  METHODS
  This was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial) were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, α4β7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test.
  
  
  RESULTS
  Among 181 adults, 36 (20%) died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group.
  
  
  CONCLUSIONS
  Specific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention.
authors.affiliation: Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia; NUSTART project, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Chisenga
authors.affiliation: NUSTART project, University Teaching Hospital, Lusaka, Zambia; London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Filteau
authors.affiliation: NUSTART project, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Joshua
authors.initials: J
authors.lastname: Siame
authors.affiliation: NUSTART project, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Molly
authors.initials: M
authors.lastname: Chisenga
authors.affiliation: Barts & The London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Prendergast
authors.affiliation: Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia; NUSTART project, University Teaching Hospital, Lusaka, Zambia; London School of Hygiene & Tropical Medicine, London, United Kingdom; Barts & The London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality*; D006801:Humans; D008297:Male; D044342:Malnutrition / Q000150:complications*; D008903:Minerals / Q000627:therapeutic use; D011379:Prognosis; D012017:Referral and Consultation; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D014815:Vitamins / Q000627:therapeutic use; D015024:Zambia
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D008903:Minerals; D014815:Vitamins