title: Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia.
abstract: BACKGROUND
  A low body mass index (BMI) at antiretroviral therapy (ART) initiation is a strong predictor of mortality among HIV-infected adults in resource-constrained settings. The relationship between nutrition and inflammation-related serum biomarkers and early treatment outcomes (e.g., less than 90 days) in this population is not well described.
  
  
  METHODS
  An observational cohort of 142 HIV-infected adults in Lusaka, Zambia, with BMI under 16 kg/m2 or CD4+ lymphocyte counts of less than 50 cells/mm3, or both, was followed prospectively during the first 12 weeks of ART. Baseline and serial post-treatment phosphate, albumin, ferritin and highly sensitive C-reactive protein (hsCRP) serum levels were measured. The primary outcome was mortality.
  
  
  RESULTS
  Lower baseline phosphate and albumin serum levels, and higher ferritin and hsCRP, were significantly associated with mortality prior to 12 weeks (p<0.05 for all comparisons), independent of known risk factors for early ART-associated mortality in sub-Saharan Africa. The time-dependent interval change in albumin was associated with mortality after adjusting for the baseline value (AHR 0.62 [0.43, 0.89] per 5 g/L increase), but changes in the other biomarkers were not.
  
  
  CONCLUSIONS
  The predictive value of serum biomarkers for early mortality in a cohort of adults with malnutrition and advanced HIV in a resource-constrained setting was primarily driven by pre-treatment values, rather than post-ART changes. Interventions to promote earlier HIV diagnosis and treatment, address nutritional deficiencies, and identify the etiologies of increased systemic inflammation may improve ART outcomes in this vulnerable population.
authors.affiliation: Centre for Infectious Diseases Research in Zambia, Plot 1275 Lubuto Road, Lusaka, Zambia. john.r.koethe@vanderbilt.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Koethe
authors.forename: Meridith
authors.initials: M
authors.lastname: Blevins
authors.forename: Christopher
authors.initials: C
authors.lastname: Nyirenda
authors.forename: Edmond K
authors.initials: EK
authors.lastname: Kabagambe
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.forename: C William
authors.initials: CW
authors.lastname: Wester
authors.forename: Isaac
authors.initials: I
authors.lastname: Zulu
authors.forename: Janelle M
authors.initials: JM
authors.lastname: Chiasera
authors.forename: Lloyd B
authors.initials: LB
authors.lastname: Mulenga
authors.forename: Albert
authors.initials: A
authors.lastname: Mwango
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Heimburger
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D018791:CD4 Lymphocyte Count; D005260:Female; D005293:Ferritins / Q000097:blood; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008297:Male; D044342:Malnutrition / Q000150:complications* / Q000473:pathology*; D010710:Phosphates / Q000097:blood; D011237:Predictive Value of Tests; D011446:Prospective Studies; D044967:Serum / Q000737:chemistry; D012709:Serum Albumin / Q000032:analysis; D016896:Treatment Outcome; D015024:Zambia
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D010710:Phosphates; D012709:Serum Albumin; D002097:C-Reactive Protein; D005293:Ferritins