title: The immunomodulatory nutritional intervention NR100157 reduced CD4+ T-cell decline and immune activation: a 1-year multicenter randomized controlled double-blind trial in HIV-infected persons not receiving antiretroviral therapy (The BITE Study).
abstract: BACKGROUND
  The immunomodulatory nutritional product NR100157 was developed for human immunodeficiency virus (HIV)-infected individuals. We hypothesized that targeting the compromised gastrointestinal tract of HIV-infected individuals would result in systemic immunological benefits.
  
  
  METHODS
  In a multicenter, randomized, controlled, double-blind trial, 340 HIV-1-positive adults not on antiretroviral therapy, with CD4(+) T-cell counts <800/µL, were given either NR100157 or an isocaloric and isonitrogenous control for 52 weeks. Primary outcome was CD4(+) T-cell count. Secondary outcomes included plasma viral load (pVL), safety, and tolerability. In a pilot study (n = 20), levels of CD4(+)CD25(+) and CD8(+)CD38(+) activation were measured (n = 20). The trial is registered at the Dutch Trial Register (NTR886) and ISRCTN81868024.
  
  
  RESULTS
  At 52 weeks, CD4(+) T-cell decline showed a 40-cell/µL difference (P = .03) in the intention-to-treat population in favor of the immunomodulatory NR100157 (control vs active, -68 ± 15 vs -28 ± 16 cells/µL/year). The change in pVL from baseline was similar between groups (P = .81). In the pilot study, the percentage of CD4(+)CD25(+) was lower in the active group (P < .05) and correlated with changes in CD4(+) T-cell count (r = -0.55, P < .05). The percentage of CD8(+)CD38(+) levels was unaffected.
  
  
  CONCLUSIONS
  The specific immunonutritional product NR100157 significantly reduces CD4(+) decline in HIV-1-infected individuals, and this is associated with decreased levels of CD4(+)CD25(+). (This nutritional intervention is likely to affect local gut integrity and gut-associated lymphoid tissue homeostasis, which in turn translates positively to systemic effects.) Clinical Trials Registration. ISRCTN81868024.
authors.affiliation: Fundación Huésped, Buenos Aires, Argentina.
authors.forename: P
authors.initials: P
authors.lastname: Cahn
authors.forename: K
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: B
authors.initials: B
authors.lastname: Gazzard
authors.forename: R S
authors.initials: RS
authors.lastname: Diaz
authors.forename: A
authors.initials: A
authors.lastname: Gori
authors.forename: D P
authors.initials: DP
authors.lastname: Kotler
authors.forename: A
authors.initials: A
authors.lastname: Vriesema
authors.forename: N A
authors.initials: NA
authors.lastname: Georgiou
authors.forename: J
authors.initials: J
authors.lastname: Garssen
authors.forename: M
authors.initials: M
authors.lastname: Clerici
authors.forename: J M A
authors.initials: JM
authors.lastname: Lange
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004032:Diet / Q000009:adverse effects / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010949:Plasma / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D007155:Immunologic Factors
keywords: CD4 decline; NR100157; immune activation; immunonutrition