Funded projects

Please note that this is not an exhaustive list and is a work-in-progress. Updates will continue to be made to encompass all TB-related projects for CTB faculty. 



The Role of Alcohol Use in Incident TB Infection and Active TB Disease Among Persons Living with HIV
PI:
Judith Hahn
Project Number: P01AA029541
Source of Support: NIH
Start/End Dates: 2021-2026
https://reporter.nih.gov/search/-SRD6OUHHkGvrd5m4Vc1rQ/project-details/10303986
Tuberculosis (TB) is the leading cause of death among persons living with HIV (PLWH); TB disease rates for PLWH engaging in heavy alcohol use are 2-3 times those of alcohol abstainers and TB treatment outcomes are poorer. There has been little research examining the impact of alcohol use on acquiring new TB infection separately from progressing to active TB disease; this limits our ability to understand the role of alcohol use on the separate phases of TB to optimize intervention strategies most appropriate for each.We propose to examine the risk of acquiring TB infection and of incident active TB disease among PLWH with heavy alcohol use after receipt of TPT in PLWH in Uganda, a high HIV/TB country. Our goal is to inform interventions to reduce the risk for acquiring new TB infection in this group, including behavioral interventions to reduce alcohol use, and TPT strategies, such as repeat short-course TPT to prevent active TB disease. This study is part of a P01 based at BMC.

Safety and tolerability of new and repurposed drugs for MDR-TB treatment
PI:
Gustavo E. Velásquez, MD, MPH
Project Number: K08 AI141740
Source of Support: National Institute of Allergy and Infectious Diseases
Start/End Dates: 2021-2024
https://reporter.nih.gov/search/6nxH_PaOIEaD_kaMb-dhvQ/project-details/10469871
Two new drugs, bedaquiline and delamanid, and two repurposed drugs, clofazimine and linezolid, were recently recommended for multidrug-resistant tuberculosis (MDR-TB) treatment. A growing body of data is emerging from clinical trials of novel MDR-TB regimens using these drugs, yet high-quality evidence on their safety and tolerability—informed by pharmacokinetics—is sorely lacking. We will leverage existing and forthcoming data to [1] examine the safety and tolerability of bedaquiline and delamanid within conventional MDR-TB regimens; [2] estimate the effect of linezolid-dose reduction strategies on the safety and tolerability of MDR-TB treatment and the pharmacokinetics of linezolid; and [3] estimate the effect of plasma drug exposure on the safety and tolerability of combinations of new and repurposed drugs in a Phase 3 trial. Transferred in from Brigham and Women's Hospital.

Tuberculosis Epidemiologic Studies Consortium III
PI:
Priya B. Shete MD MPH, and Jennifer Flood MD MPH
Source of Support: CDC
Start/End Dates: 2021-2026
This CDC funded research study is being implemented by UCSF at North East Medical Services, a Federally Qualified Health Center in the San Francisco Bay Area.   The project is a collaboration with the California Department of Public Health and the San Francisco TB program.  The overall objective is to  evaluate the impact of interventions implemented to increase the proportion of non-US born individuals with latent tuberculosis infection who are diagnosed and treated. Using implementation science approaches, the study will prioritize the barriers/facilitators to target and then evaluate the effectiveness of the intervention on closing the gaps in the LTBI cascade of care. The impact of this work will be to identify scalable interventions that will reduce the burden of latent TB among immigrant communities, currently the population most at risk for active TB in the United States. 

Novel Biomarkers to Shorten TB Treatment
PI:
Rada Savic, PhD
Source of Support: Rutgers /NIH/NIAID 
Project Number: R01AI126788
Start/End Dates: 2016-2022
The goal of this project is to develop first comprehensive predictive model of TB treatment response and cure incorporating genome load, pre-treatment MIC and host pharmacokinetics, and identify genomic and transcriptional markers that can replace bacterial MIC with a rapid pre-treatment test.

Meeting report for the technical consultation on pharmacokinetics
PI:
Savic, R.M.
Status of Support: Completed
Project Number: 2020/1079860-0
Source of Support: World Health Organization (WHO)
Start/End Dates: 2020-2021
Conduct a series of systematic reviews on the available evidence for the optimal dosing of first-line TB medicines in children.

TB Drug Lesion Penetration and Translational Modeling
PI:
Savic, R.M.
Project Number: INV-002483
Source of Support: Bill & Melinda Gates Foundation
Start/End Dates: 2019-2022
The purpose of this project is to evaluate the penetration of TB drugs at the site of infection and inform improved translational approaches.

Better Evidence and Formulations for Improved MDR-TB Treatment for Children (BENEFIT Kids)
PI:
Garcia-Prats, Savic, R.M.
Project Number: A134396
Source of Support: UNITAID
Start/End Dates: 2019-2022
The goal of this project is to contribute to reduced morbidity and mortality of children with MDR-TB through better access to improved MDR-TB prevention and treatment.

Identifying Optimal Treatment Strategies for Tuberculosis Treatment
PI:
Savic, R.M., Alland
Project Number: R01AI135124-01A1
Source of Support: NIH/NIAID
Start/End Dates: 2019-2023
The goal of this proposal is to identify markers useful for assigning patients with tuberculosis (TB) to optimized treatment strategies that provide high cure rates and maximal safety and tolerability.

Drug regimen optimization for new and existing TB drugs
PI:
Savic, R.M.
Project Number: A136512
Source of Support: Global Alliance for TB Drug Development
Start/End Dates: 2021-2021
The major goals of this project are to optimize multidrug regimens for new and existing TB drugs by using data-driven modeling approach that can integrate non-clinical and early clinical data including assessing the dose and efficacy relationship after administration in patients with pulmonary XDR-TB.

Accelerating evaluation and development of new combination tuberculosis drug treatments
PI:
Savic, R.M., Nahid, P.
Project Number: A136030
Source of Support: Denver Research Institute, Inc
Start/End Dates: 2019-2022
The project will further characterize a novel test to better prioritize among candidate tuberculosis (TB) combination drug regimens.