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.
Departments of *Immunology; and
†Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Correspondence to: Karen A. Norris, PhD, Department of Immunology, HIV Lung Research Center, University of Pittsburgh, 1057 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15261 (e-mail: firstname.lastname@example.org).
Presented in part at the American Thoracic Society International Conference, May 22, 2012, San Francisco, CA.
Supported by the National Institutes of Health (NIH) Grant HL077095-01A1 and HL077914-01 (K.A.N.) and NIH training Grant T32 AI49820 (H.M.K.).
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The authors have no conflicts of interest to disclose.
Received September 10, 2013
Accepted September 10, 2013