Although the technology to study microbial communities is available, it has yet to be applied comprehensively to the HIV-infected respiratory tract. Our central hypothesis is that the microbiome of the lung is shaped by HIV infection, the degree of HIV-mediated immunosuppression, and the use of antiretroviral and antimicrobial therapies. Furthermore, we hypothesize that the microbiome of the lung changes between periods of health and pneumonia, and that the presence of specific microbes or microbial onsortia within the lung is associated with the development of HIV-associated pulmonary complications and mortality. We propose a series of cross-sectional and longitudinal studies to characterize the bacterial, viral, and fungal microbiome present in the lungs of patients with acute and early HIV infection, chronic HIV infection, and opportunistic pneumonia. We propose to use three microarrays, the 16S rRNA PhyloChip, ViroChip, and 18S rRNA MycoChip as economical, standardized tools to provide a high resolution profile of the microbiome in a large number of HIV patient samples. To complement the microarray analysis and obtain functional profiles of microbial community behavior and associated host response, we will perform next generation 454- pyrosequencing of cDNA generated from a subset of these samples. These studies will be conducted within the Options, SCOPE, and IHOP cohorts, three established and well-characterized cohorts of HIV-infected and HIV-uninfected patients based at SFGH/UCSF. We propose the following specific aims: (1): To compare the lung microbiome in subjects with and without HIV infection;(2): To determine whether the degree of HIV-mediated immunosuppression (i.e., CD4 cell count) is related to the lung microbiome of HIV-infected subjects without acute illness/pneumonia;(3) To determine the effect of initiation of antiretroviral therapy and opportunistic pneumonia prophylaxis on the lung microbiome of HIV-infected subjects over time;(4) To determine the effects of opportunistic pneumonia and accompanying opportunistic pneumonia treatment on the lung microbiome of HIV-infected subjects over time;and (5) To correlate lung microbiome composition and function with HIV-associated morbidity and mortality.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL098964-05
Application #
8521355
Study Section
Special Emphasis Panel (ZHL1-CSR-Z (S1))
Program Officer
Colombini-Hatch, Sandra
Project Start
2009-09-25
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$694,210
Indirect Cost
$238,359
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Drummond, M Bradley; Kunisaki, Ken M; Huang, Laurence (2016) Obstructive Lung Diseases in HIV: A Clinical Review and Identification of Key Future Research Needs. Semin Respir Crit Care Med 37:277-88
Mar, Jordan S; LaMere, Brandon J; Lin, Din L et al. (2016) Disease Severity and Immune Activity Relate to Distinct Interkingdom Gut Microbiome States in Ethnically Distinct Ulcerative Colitis Patients. MBio 7:
Shenoy, Meera K; Iwai, Shoko; Lin, Din L et al. (2016) Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in HIV-Pneumonia Patients. Am J Respir Crit Care Med :
Juliano, Jonathan J; Barnett, Eric; Parobek, Christian M et al. (2015) Use of Oropharyngeal Washes to Diagnose and Genotype Pneumocystis jirovecii. Open Forum Infect Dis 2:ofv080
Beck, James M; Schloss, Patrick D; Venkataraman, Arvind et al. (2015) Multicenter Comparison of Lung and Oral Microbiomes of HIV-infected and HIV-uninfected Individuals. Am J Respir Crit Care Med 192:1335-44
Cui, Lijia; Morris, Alison; Huang, Laurence et al. (2014) The microbiome and the lung. Ann Am Thorac Soc 11 Suppl 4:S227-32
Iwai, Shoko; Huang, Delphine; Fong, Serena et al. (2014) The lung microbiome of Ugandan HIV-infected pneumonia patients is compositionally and functionally distinct from that of San Franciscan patients. PLoS One 9:e95726
Parobek, Christian M; Jiang, Linda Y; Patel, Jaymin C et al. (2014) Multilocus microsatellite genotyping array for investigation of genetic epidemiology of Pneumocystis jirovecii. J Clin Microbiol 52:1391-9
Merenstein, Daniel; El-Nachef, Najwa; Lynch, Susan V (2014) Fecal microbial therapy: promises and pitfalls. J Pediatr Gastroenterol Nutr 59:157-61
Mar, Jordan S; Nagalingam, Nabeetha A; Song, Yuanlin et al. (2014) Amelioration of DSS-induced murine colitis by VSL#3 supplementation is primarily associated with changes in ileal microbiota composition. Gut Microbes 5:494-503

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