My long-term goal is to become an independent investigator focusing on novel, cost- effective strategies for the detection and control of HIV and tuberculosis (TB). During the award period, I will build expertise in the methodology and conduct of clinical investigation, infectious disease modeling and economic evaluation. My career development plan combines formal didactics with relevant research experiences that address global HIV/TB priorities. A cross-disciplinary team of recognized leaders in HIV /TB research will provide professional and scientific mentorship during this phase of career development. Research: Effective control of TB and MDR-TB in HIV patients is hindered by low case-detection rates. Intensified Case Finding (ICF) of TB is advocated by the WHO as a strategy for HIV/TB control, but critical knowledge gaps exist. First, it is unknown if ICF of TB in HIV patients will increase case-detection and reduce HIV/TB mortality. Second, the optimal usage of emerging, rapid TB diagnostic tools as part of future ICF algorithms is not clear. Finally, the cost-effectiveness of novel ICF interventions has yet to be elucidated.
The Aims of this proposal are: 1) To determine the impact of standardized TB ICF on HIV patient outcomes. ICF using a standardized TB screening/diagnostic strategy recently recommended by the WHO will be implemented for a longitudinal cohort of HIV patients in Uganda. TB case-detection and HIV/TB mortality rates will be assessed using a pre/post study design. 2) To determine the comparative- effectiveness of ICF algorithms that utilize new rapid TB diagnostic tools. We will evaluate the comparative accuracy of the urine LAM-ELISA, Lateral-Flow LAM, and Cepheid Xpert rapid diagnostic tests among TB suspects in Uganda. Decision-analysis will be used to estimate the accuracy, efficiency, and yield of ICF algorithms that incorporate combinations of these tools [with/without conventional diagnostics] either serially and/or in parallel. 2) To model the impact, costs, and cost-effectiveness of incorporating novel, rapid TB diagnostics into ICF algorithms. We will model the impact of novel ICF interventions on population TB incidence, prevalence, and mortality in HIV-prevalent regions, and perform an economic evaluation to guide cost-effective placement of novel, rapid TB diagnostics in the health system. Environment: Johns Hopkins University offers substantial intellectual and physical resources. The Division of Infectious Diseases has over 50 full-time faculty including leaders in international HIV and TB research. The JH Center for TB Research further provides a unique research infrastructure with multi-disciplinary faculty, extensive international partnerships, and over 5,500 square feet of new lab and office space. Johns Hopkins Public Health School is the largest such institution in the world and offers intensive coursework in all aspects of clinical research design, management, and analysis, including economic evaluation of health interventions. This comprehensive portfolio will facilitate development as an independent clinical investigator.

Public Health Relevance

/Relevance The TB and HIV co-epidemic has resulted in serious global morbidity and mortality and new strategies are needed for HIV/TB detection and control. A key challenge to HIV/TB control is low TB case-detection rates due to clinical disease heterogeneity and slow, insensitive TB diagnostic modalities. The proposed studies will evaluate the impact of implementing standardized TB intensified case-finding algorithm on HIV patient outcomes, and determine the optimal usage of novel, rapid TB diagnostics for HIV prevalent settings.

Agency
National Institute of Health (NIH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI089259-04
Application #
8610872
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Srinivasan, Sudha
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Nakiyingi, Lydia; Moodley, Vineshree Mischka; Manabe, Yukari C et al. (2014) Diagnostic accuracy of a rapid urine lipoarabinomannan test for tuberculosis in HIV-infected adults. J Acquir Immune Defic Syndr 66:270-9

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