title: Trimethoprim-sulfamethoxazole treatment does not reverse obstructive pulmonary changes in pneumocystis-colonized nonhuman primates with SHIV infection.
abstract: BACKGROUND
  Despite antiretroviral therapy and trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, Pneumocystis pneumonia remains an important serious opportunistic infection in HIV-infected persons. Pneumocystis (Pc) colonization in HIV-infected individuals and in HIV-uninfected smokers is associated with chronic obstructive pulmonary disease (COPD). We previously developed a nonhuman primate model of HIV infection and Pc colonization and demonstrated that Pc colonization correlated with COPD development. In the present study, we examined kinetics of COPD development in non-human primate and tested the effect of Pc burden reduction on pulmonary function by TMP-SMX treatment.
  
  
  METHODS
  Cynomolgus macaques (n = 16) were infected with simian/human immunodeficiency virus (SHIV89.6P), and natural Pc colonization was examined by nested polymerase chain reaction of serial bronchoalveolar lavage fluid and anti-Pc serology.
  
  
  RESULTS
  Eleven of 16 monkeys became Pc colonized by 16 weeks post simian-human immunodeficiency virus (SHIV) infection. Pc colonization of SHIV-infected monkeys led to progressive declines in pulmonary function as early as 4 weeks after Pc detection. SHIV-infected and Pc-negative monkeys maintained normal lung function. At 25 weeks post-SHIV infection, TMP-SMX treatment was initiated in 7 Pc-positive (Pc+) (TMP: 20 mg/kg and SMX: 100 mg/kg, daily for 48 weeks) and 5 Pc-negative (Pc-) monkeys. Four SHIV+/Pc+ remained untreated for the duration of the experiment. Detection frequency of Pc in serial bronchoalveolar lavage fluid (P < 0.001), as well as plasma Pc antibody titers (P = 0.02) were significantly reduced in TMP-SMX-treated macaques compared with untreated.
  
  
  CONCLUSIONS
  Reduction of Pc colonization by TMP-SMX treatment did not improve pulmonary function, supporting the concept that Pc colonization results in early, permanent obstructive changes in the lungs of immunosuppressed macaques.
authors.affiliation: Departments of *Immunology; and †Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Kling
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Shipley
authors.forename: Siobhan
authors.initials: S
authors.lastname: Guyach
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tarantelli
authors.forename: Alison
authors.initials: A
authors.lastname: Morris
authors.forename: Karen A
authors.initials: KA
authors.lastname: Norris
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000908:Antibodies, Fungal / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D008173:Lung Diseases, Obstructive / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008251:Macaca; D011010:Pneumocystis / Q000235:genetics / Q000302:isolation & purification; D016720:Pneumocystis Infections / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications*; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
chemical_list: D000890:Anti-Infective Agents; D000908:Antibodies, Fungal; D015662:Trimethoprim, Sulfamethoxazole Drug Combination