Gut microbiota in HIV-pneumonia patients is related to peripheral CD4 counts, lung microbiota, and in vitro macrophage dysfunction.

Pneumonia is common and frequently fatal in HIV-infected patients, due to rampant, systemic inflammation and failure to control microbial infection. While airway microbiota composition is related to local inflammatory response, gut microbiota has been shown to correlate with the degree of peripheral immune activation (IL6 and IP10 expression) in HIV-infected patients. We thus hypothesized that both airway and gut microbiota are perturbed in HIV-infected pneumonia patients, that the gut microbiota is related to peripheral CD4+ cell counts, and that its associated products differentially program immune cell populations necessary for controlling microbial infection in CD4-high and CD4-low patients.

Effects of clinical and environmental factors on bronchoalveolar antibody responses to Pneumocystis jirovecii: A prospective cohort study of HIV+ patients.

Background: Humoral immunity plays an important role against Pneumocystis jirovecii infection, yet clinical and environmental factors that impact bronchoalveolar antibody responses to P. jirovecii remain uncertain.

Methods: From October 2008-December 2011 we enrolled consecutive HIV-infected adults admitted to San Francisco General Hospital (SFGH) who underwent bronchoscopy for suspected Pneumocystis pneumonia (PCP).

Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in Patients with HIV and Pneumonia.

Rationale: The potential role of the airway microbiota in dictating immune responses and infection outcomes in HIV-associated pneumonia is largely unknown.

Objectives: To investigate whether microbiologically and immunologically distinct subsets of patients with HIV and pneumonia exist and are related to mortality.

Methods: Bronchoalveolar lavage samples from Ugandan patients with HIV and pneumonia (n = 182) were obtained at study enrollment (following antibiotic treatment); patient demographics including 8- and 70-day mortality were collected.

Use of Oropharyngeal Washes to Diagnose and Genotype Pneumocystis jirovecii.

Pneumocystis jirovecii is a symbiotic respiratory fungus that presents in 2 clinical forms: pneumonia in immunocompromised patients or colonization, defined by the presence of the organism without associated clinical symptoms. Currently, diagnosis requires invasive bronchoscopy, which may not be available in some settings and is inappropriate for detecting colonization in healthy individuals. Noninvasive diagnostic techniques and molecular strain typing tools that can be used on these samples are critical for conducting studies to better understand transmission.

Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease.

Rationale: Microbiome studies typically focus on bacteria, but fungal species are common in many body sites and can have profound effects on the host. Wide gaps exist in the understanding of the fungal microbiome (mycobiome) and its relationship to lung disease.

Objectives: To characterize the mycobiome at different respiratory tract levels in persons with and without HIV infection and in HIV-infected individuals with chronic obstructive pulmonary disease (COPD).

The lung microbiome of Ugandan HIV-infected pneumonia patients is compositionally and functionally distinct from that of San Franciscan patients.

Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco).

Multilocus microsatellite genotyping array for investigation of genetic epidemiology of Pneumocystis jirovecii.

Pneumocystis jirovecii is a symbiotic respiratory fungus that causes pneumonia (PcP) in immunosuppressed patients. Because P. jirovecii cannot be reliably cultured in vitro, it has proven difficult to study and gaps in our understanding of the organism persist.

Ambient air pollution associated with suppressed serologic responses to Pneumocystis jirovecii in a prospective cohort of HIV-infected patients with Pneumocystis pneumonia.

Background: Ambient air pollution (AAP) may be associated with increased risk for Pneumocystis pneumonia (PCP). The mechanisms underlying this association remain uncertain.

Objectives: To determine if real-life exposures to AAP are associated with suppressed IgM antibody responses to P.

Antibody responses against Pneumocystis jirovecii in health care workers over time.

In a previous cross-sectional study, we showed that clinical staff working in a hospital had significantly higher antibody levels than nonclinical staff to Pneumocystis jirovecii. We conducted a longitudinal study, described here, to determine whether occupation and self-reported exposure to a patient with P. jirovecii pneumonia were associated with antibody levels to P.

HIV infection is associated with diffusing capacity impairment in women.

Respiratory dysfunction is common with HIV infection, but few studies have directly assessed whether HIV remains an independent risk factor for pulmonary function abnormalities in the antiretroviral therapy era. Additionally, few studies have focused on pulmonary outcomes in HIV+ women. We tested associations between risk factors for respiratory dysfunction and pulmonary outcomes in 63 HIV+ and 36 HIV-uninfected women enrolled in the Women's Interagency HIV Study.

Dihydropteroate synthase mutations in Pneumocystis pneumonia: impact of applying different definitions of prophylaxis, mortality endpoints and mutant in a single cohort.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are well-reported. Although sulfa prophylaxis generally is associated with DHPS mutant infection, whether mutant infection is associated with poorer clinical outcomes is less clear. The differing definitions of sulfa prophylaxis and the different mortality endpoints used in these studies may be one explanation for the conflicting study results.

Environmental risk factors for Pneumocystis pneumonia hospitalizations in HIV patients.

Background: Pneumocystis pneumonia (PcP) is the second leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients in the United States. Although the host risk factors for the development of PcP are well established, the environmental (climatological, air pollution) risk factors are poorly understood. The major goal of this study was to determine the environmental risk factors for admissions of HIV-positive patients with PcP to a single medical center.

Oral and airway microbiota in HIV-infected pneumonia patients.

Despite the increased frequency of recurrent pneumonia in HIV-infected patients and recent studies linking the airway bacterial community (microbiota) to acute and chronic respiratory infection, little is known of the oral and airway microbiota that exist in these individuals and their propensity to harbor pathogens despite antimicrobial treatment for acute pneumonia. This pilot study compared paired samples of the oral and airway microbiota from 15 hospitalized HIV-infected patients receiving antimicrobial treatment for acute pneumonia. Total DNA was extracted, bacterial burden was assessed by quantitative PCR, and amplified 16S rRNA was profiled for microbiome composition using a phylogenetic microarray (16S rRNA PhyloChip).

Serum antibody levels to the Pneumocystis jirovecii major surface glycoprotein in the diagnosis of P. jirovecii pneumonia in HIV+ patients.

Background: Pneumocystis jirovecii remains an important cause of fatal pneumonia (Pneumocystis pneumonia or PcP) in HIV+ patients and other immunocompromised hosts. Despite many previous attempts, a clinically useful serologic test for P. jirovecii infection has never been developed.