title: Increased systemic inflammation is associated with cardiac and vascular dysfunction over the first 12 weeks of antiretroviral therapy among undernourished, HIV-infected adults in Southern Africa.
abstract: BACKGROUND
  Persistent systemic inflammation is associated with mortality among undernourished, HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa, but the etiology of these deaths is not well understood. We hypothesized that greater systemic inflammation is accompanied by cardiovascular dysfunction over the first 12 weeks of ART.
  
  
  METHODS
  In a prospective cohort of 33 undernourished (body mass index <18.5 kg/m2) Zambian adults starting ART, we measured C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 and CD14 at baseline and 12 weeks. An EndoPAT device measured the reactive hyperemia index (LnRHI; a measure of endothelial responsiveness), peripheral augmentation index (AI; a measure of arterial stiffness), and heart rate variability (HRV; a general marker of autonomic tone and cardiovascular health) at the same time points. We assessed paired changes in inflammation and cardiovascular parameters, and relationships independent of time point (adjusted for age, sex, and CD4+ T-cell count) using linear mixed models.
  
  
  RESULTS
  Serum CRP decreased (median change -3.5 mg/l, p=0.02), as did TNF-α R1 (-0.31 ng/ml, p<0.01), over the first 12 weeks of ART. A reduction in TNF-α R1 over 12 weeks was associated with an increase in LnRHI (p=0.03), and a similar inverse relationship was observed for CRP and LnRHI (p=0.07). AI increased in the cohort as a whole over 12 weeks, and a reduction in sCD163 was associated with a rise in the AI score (p=0.04). In the pooled analysis of baseline and 12 week data, high CRP was associated with lower HRV parameters (RMSSD, p=0.01; triangular index, p<0.01), and higher TNF- α R1 accompanied lower HRV (RMSSD, p=0.07; triangular index, p=0.06).
  
  
  CONCLUSIONS
  Persistent inflammation was associated with impaired cardiovascular health over the first 12 weeks of HIV treatment among undernourished adults in Africa, suggesting cardiac events may contribute to high mortality in this population.
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bestawros
authors.affiliation: University Teaching Hospital, Lusaka, Zambia.
authors.forename: Takondwa
authors.initials: T
authors.lastname: Chidumayo
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Meridith
authors.initials: M
authors.lastname: Blevins
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University, Nashville, TN, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Canipe
authors.affiliation: Vanderbilt Institute for Global Health, Nashville, TN, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Bala
authors.affiliation: University Teaching Hospital, Lusaka, Zambia ; Barts & the London School of Medicine, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Filteau
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.affiliation: Vanderbilt Institute for Global Health, Nashville, TN, USA.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Heimburger
authors.affiliation: Vanderbilt Institute for Global Health, Nashville, TN, USA ; Division of Infectious Diseases, Vanderbilt University, Nashville, TN, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Koethe
keywords: HIV; antiretroviral therapy; cardiovascular; inflammation; nutrition; sub-Saharan Africa