Open Forum Infectious Diseases Advance Access published February 18, 2016
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Absence of Pneumocystis jirovecii colonization in HIV-infected individuals with and without airway obstruction and with undetectable viral load
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Andreas Ronit1, Ditte Marie Klitbo1, Anna Overgaard Kildemoes5, Thomas Benfield2, Jan Gerstoft1, Jørgen Vestbo3, Jørgen Skov Jensen4, Jørgen Kurtzhals5, and Susanne Dam
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Nielsen1
Viro-immunology Research Unit, Department of Infectious Diseases 8632, Copenhagen University
Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
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Centre for Respiratory Medicine and Allergy, University Hospital South Manchester NHS
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Foundation Trust and The University of Manchester, Manchester, UK Department of Microbiology and Infection control, Statens Serum Institut, Copenhagen, Denmark
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Centre for Medical Parasitology, Department of Clinical Microbiology KMA 7602, Copenhagen
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University Hospital, and Department of Immunology and Microbiology, University of Copenhagen,
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Copenhagen, Denmark
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Corresponding author: Susanne Dam Nielsen, Ass. Professor, MD, DMSc, Viro-immunology Research Unit, Department of Infectious Diseases 8632, Copenhagen University Hospital,
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Blegdamsvej 9B; DK-2100 Copenhagen Ø; Denmark. E-Mail:
[email protected]; Phone: (+45) 3545 0859, Fax: (+45) 3545 6648
© The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-ncnd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact
[email protected].
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Hospital, Copenhagen, Denmark
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Abstract Pneumocystis jirovecii colonization has been associated with non-AIDS pulmonary
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comorbidity. We used spirometry to measure pulmonary function and analyzed oral wash specimens by quantitative polymerase chain reaction (qPCR) targeting the large mitochondrial
ribosomal subunit. For sensitivity control, a blinded subsample was subjected to touch-down PCRs, targeting both large and small ribosomal subunits and the major surface glycoprotein (MSG). P.
infected individuals confirmed by all PCR methods. Thus, prevalence of P. jirovecii colonization was low and unlikely to be a major cause of pulmonary comorbidity in this group
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of well-treated HIV-infected individuals.
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jirovecii DNA was detected in 1 of 156 (95%CI: 0.1-3.5%) virologically suppressed HIV-
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INTRODUCTION With the widespread use of combination anti-retroviral therapy (cART) the incidence of
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Pneumocystis pneumonia (PCP) has decreased [1], albeit PCP remains a common AIDS-defining
opportunistic infection [2]. Moreover, colonization with P. jirovecii has been linked to non-AIDS
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pulmonary comorbidity in HIV-infected individuals in the cART era [3].
Chronic obstructive pulmonary disease (COPD) is more prevalent in HIV-infected individuals
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ART era PCP was recognized as a risk factor for subsequent airway obstruction [5]. Furthermore, evidence from the early cART era suggested that P. jirovecii colonization may be an independent risk factor of developing HIV-associated COPD [6]. However, studies of P. jirovecii colonization
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were unable to determine causality.
The prevalence of P. jirovecii colonization has been investigated in several HIV-infected and
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uninfected populations. In the early cART era, the prevalence of colonization varied from 10-70% depending on the population studied [3]. However, most studies included HIV-infected individuals
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with profound immunodeficiency, respiratory symptoms, or acquired immune deficiency syndrome
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(AIDS) [3].
In this study, we determined the prevalence of P. jirovecii colonization in a cohort of cART-treated
HIV-infected individuals with and without airway obstruction using two independent PCR methods and spirometry. We hypothesized that P. jirovecii colonization would be detectable even in welltreated individuals and a higher prevalence would be found in those with COPD.
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compared to uninfected individuals [4], but the underlying mechanisms are unclear. In the pre-
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Methods Patients
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This study was approved by the Committee on Health Research Ethics of the Capital Region of
Denmark (protocol no. H-8-2014-004), and performed in accordance with the Helsinki Declaration. Oral and written informed consent was obtained from all patients prior to participation. The study
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was registered at clinicaltrials.gov (NCT02382822) as part of the ongoing Copenhagen
Comorbidity Study in HIV infection (COCOMO). Initially, we planned to study colonization
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from May-October 2015. All participants were recruited from the University of Copenhagen outpatient clinics at Rigshospitalet and Hvidovre Hospital.
Data collection
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Information about HIV-related variables including CD4 T cell count, HIV viral load, previous PCP, intravenous drug use (IDU), and co-infection with hepatitis C virus (HCV) were retrieved from
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patient records. All participants completed a questionnaire that included information on tobacco
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exposure and use of inhaled medication.
Spirometry
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Spirometry was performed using an EasyOne® ultrasonic spirometer (ndd Medizintechnik, Zürich, Switzerland) in accordance with ATS/ERS guidelines [7]. For bronchodilation (in patients with a ratio between forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC)
