title: Trimethoprim-sulfamethoxazole exposure alters ex vivo function of B lymphocytes isolated from human immunodeficiency virus-infected patients receiving Zidovudine.
abstract: OBJECTIVE
  To determine if exposure to trimethoprim-sulfamethoxazole (TMP-SMX) causes a defect in peripheral B-cell function among patients with the human immunodeficiency virus (HIV) who are receiving zidovudine antiretroviral therapy.
  
  
  METHODS
  Prospective, single-center, single-group, case-crossover design with a 4-week exposure period.
  
  
  METHODS
  University-affiliated infectious diseases outpatient clinic.
  
  
  METHODS
  Fourteen HIV-infected adult men receiving zidovudine, who had CD4(+) cell counts above 350 cells/mm(3) and undetectable viral loads.
  
  
  METHODS
  Patients were administered a 28-day course of TMP 160 mg-SMX 800 mg/day (one double-strength tablet/day). Peripheral blood mononuclear cells (PBMCs) were obtained and isolated before and after exposure to TMP-SMX. Cells were cultured ex vivo with three mitogens of differing immunologic properties: pokeweed mitogen ([PWM] T-cell-dependent B-cell mitogen), Staphylococcus aureus Cowan ([SAC] T-cell-independent B-cell mitogen), and phytohemagglutinin A ([PHA] T-cell mitogen). Functionality of the B and T lymphocytes was then assessed.
  
  
  RESULTS
  Proliferative capacity, cytokine secretion, and antibody production were measured and compared before and after TMP-SMX exposure. Reduced proliferative capacities of both PBMC and B cells stimulated with mitogens were observed at the 3-day culture time point in response to PWM, PHA, and SAC (p=0.029, 0.028, and 0.026, respectively). Proliferative capacity at day 7 of culture was not significantly different for any condition examined. Cytokine production was not altered by combination drug exposure after 10 days of culture when cells were stimulated with either PWM or PHA. Although antibody responses to PWM and PHA were similar, total immunoglobulin G concentration was lower in cells stimulated with SAC in samples obtained after TMP-SMX regimen completion compared with those obtained before exposure (p=0.005).
  
  
  CONCLUSIONS
  Although these data were affected by limitations in power and study design, they suggest that peripheral B-lymphocyte function is altered as a result of TMP-SMX exposure in HIV-infected patients concurrently receiving zidovudine. Further study of this effect is warranted.
authors.affiliation: Department of Pharmacy Practice, University of Kentucky Chandler Medical Center, Lexington, Kentucky, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Venugopalan
authors.forename: Alice C
authors.initials: AC
authors.lastname: Thornton
authors.forename: Douglass T
authors.initials: DT
authors.lastname: Steinke
authors.forename: Robert P
authors.initials: RP
authors.lastname: Rapp
authors.forename: Frank
authors.initials: F
authors.lastname: Romanelli
authors.forename: David J
authors.initials: DJ
authors.lastname: Feola