title: Early immunologic failure is associated with early mortality among advanced HIV-infected adults initiating antiretroviral therapy with active tuberculosis.
abstract: BACKGROUND
  The relationship between antiretroviral therapy (ART) response and early mortality after ART initiation is unknown. We hypothesized that early mortality is associated with decreased early immunologic response to ART.
  
  
  METHODS
  We prospectively determined the association between changes in plasma human immunodeficiency virus type 1 (HIV-1) RNA and CD4(+) T-cell counts (CD4 count) after 4 weeks of ART and early mortality in adults with pulmonary tuberculosis and pre-ART CD4 counts ≤ 125 cells/µL. Purified protein derivative (PPD)-specific immune recovery was determined by interferon-γ enzyme-linked immunosorbent spot assays. Levels of interleukin 6, C-reactive protein, and soluble CD14 were assessed. Patients with CD4 count and viral load values at baseline and week 4 were analyzed using multiple logistic regression.
  
  
  RESULTS
  Early immunologic response, but not pre-ART CD4 counts or virologic response, was related to early mortality (8 [interquartile range {IQR}, -18 to 43] vs 68 [IQR, 24-131] cells/µL, P = .002). In a logistic regression model, every 20 cells/µL increase in the CD4 count from baseline to week 4 was independently associated with a 40% reduction in the odds of death (odds ratio, 0.59 [95% confidence interval, .41-.87]). PPD-specific immune recovery was lower, whereas levels of immune activation were higher, among deaths.
  
  
  CONCLUSIONS
  Early immunologic failure despite virologic suppression is associated with early mortality after ART initiation in advanced HIV/tuberculosis.
authors.affiliation: Department of Medicine, Division of Infectious Diseases.
authors.forename: Shruthi
authors.initials: S
authors.lastname: Ravimohan
authors.forename: Neo
authors.initials: N
authors.lastname: Tamuhla
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Steenhoff
authors.forename: Rona
authors.initials: R
authors.lastname: Letlhogile
authors.forename: Didimalang Kgomotso
authors.initials: DK
authors.lastname: Makutu
authors.forename: Kebatshabile
authors.initials: K
authors.lastname: Nfanyana
authors.forename: Tumelo
authors.initials: T
authors.lastname: Rantleru
authors.forename: Ann
authors.initials: A
authors.lastname: Tierney
authors.forename: Kelebogile
authors.initials: K
authors.lastname: Nkakana
authors.forename: Adam B
authors.initials: AB
authors.lastname: Schwartz
authors.forename: Robert
authors.initials: R
authors.lastname: Gross
authors.forename: Rob Roy
authors.initials: RR
authors.lastname: Macgregor
authors.forename: Scarlett L
authors.initials: SL
authors.lastname: Bellamy
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
authors.forename: Drew
authors.initials: D
authors.lastname: Weissman
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Bisson
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001902:Botswana / Q000453:epidemiology; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D019562:Viral Load; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D012367:RNA, Viral; D007371:Interferon-gamma; D002097:C-Reactive Protein
keywords: CD4 counts; HIV/AIDS; antiretroviral therapy; early mortality; immune activation; immune recovery; pathogen-specific immune recovery; sub-Saharan Africa; tuberculosis
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