In sub-Saharan Africa rates of tuberculosis (TB) and HIV infection are extremely high. TB is the leading cause of death in HIV-infected adults and often is the initial clinical manifestation. TB in HIV-infected patients carries a high risk of death which occurs predominantly in the first days to weeks after TB diagnosis [2-5]. Other severe lung infections (bacterial pneumonias, Pneumocystis, cytomegalovirus) are also major problems in people with advanced HIV disease, although incidence and coinfection rates are poorly delineated. Detailed characterization of HIV-associated lung infections is needed to improve diagnosis, to prevent new infections, and to alter this high early mortality. In settings with limited resources, understanding the interaction between TB, HIV and other respiratory co-infections in increasing morbidity and mortality will help to direct resources efficiently and to allow coinfected patients to survive long enough to access life-sparing antiretroviral (ARV) therapy. We will recruit 750 individuals from an existing fully enrolled, funded, and consented cohort of approximately 1100 patients and an additional 250 individuals using a clinical cohort established with PEPFAR funding. We will gather longitudinal data through the transition toward rapidly evolving access to pre-ARV clinical care and ARVs in Soweto, South Africa. This clinical database in collaboration with the other successful cohort databases will be a rich resource for both clinical epidemiologic studies and the study of basic pathobiologic mechanisms of HIV-associated lung complications. The proposed study is expected to provide information of fundamental importance for public policy and clinical practice, identifying effective and sustainable clinical management strategies to improve local standards of care for patients with HIV infection, to decrease early mortality after HAART and while awaiting HAART, and to identify the key target topics for future clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
3R01HL090312-05S1
Application #
8548630
Study Section
Special Emphasis Panel (ZHL1-CSR-Z (S1))
Program Officer
Peavy, Hannah H
Project Start
2007-09-28
Project End
2013-06-30
Budget Start
2012-09-26
Budget End
2013-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$285,062
Indirect Cost
$35,511
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Paximadis, Maria; Ngqobe, Refilwe N; Chaisson, Richard E et al. (2017) RICH2 is implicated in viraemic control of HIV-1 in black South African individuals. Infect Genet Evol 49:78-87
Adu-Gyamfi, Clement G; Snyman, Tracy; Hoffmann, Christopher J et al. (2017) Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human Immunodeficiency Virus-Infected Patients. Clin Infect Dis 65:1356-1358
Picton, Anabela C P; Paximadis, Maria; Chaisson, Richard E et al. (2017) CXCR6 gene characterization in two ethnically distinct South African populations and association with viraemic disease control in HIV-1-infected black South African individuals. Clin Immunol 180:69-79
Gupte, Akshay N; Wong, Michelle L; Msandiwa, Reginah et al. (2017) Factors associated with pulmonary impairment in HIV-infected South African adults. PLoS One 12:e0184530
Gornalusse, German G; Mummidi, Srinivas; Gaitan, Alvaro A et al. (2015) Epigenetic mechanisms, T-cell activation, and CCR5 genetics interact to regulate T-cell expression of CCR5, the major HIV-1 coreceptor. Proc Natl Acad Sci U S A 112:E4762-71
Hoffmann, Christopher J; Chaisson, Richard E; Martinson, Neil A (2014) Cotrimoxazole prophylaxis and tuberculosis risk among people living with HIV. PLoS One 9:e83750
Levison, Julie H; Wood, Robin; Scott, Callie A et al. (2013) The clinical and economic impact of genotype testing at first-line antiretroviral therapy failure for HIV-infected patients in South Africa. Clin Infect Dis 56:587-97
Hoffmann, Christopher J; Lewis, James J; Dowdy, David W et al. (2013) Mortality associated with delays between clinic entry and ART initiation in resource-limited settings: results of a transition-state model. J Acquir Immune Defic Syndr 63:105-11
Hoffmann, Christopher J; Variava, Ebrahim; Rakgokong, Modiehi et al. (2013) High prevalence of pulmonary tuberculosis but low sensitivity of symptom screening among HIV-infected pregnant women in South Africa. PLoS One 8:e62211
Dierberg, Kerry L; Chaisson, Richard E (2013) Human immunodeficiency virus-associated tuberculosis: update on prevention and treatment. Clin Chest Med 34:217-28

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