Investigating multiple PK and PD relationships for TB-HIV (impprove TB-HIV)

Ended Project Grant Awarded Last action

Award ID
R56AI174911
Recipient
Awarding agency
Obligated
$782,762

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date
Originally
Place of performance
Nashville, TN 37203, USA

Award details come from USAspending.gov.

Description

Abstract
Tuberculosis (TB) is the leading infectious cause of mortality globally after covid-19. TB and HIV interact synergistically, each worsening the outcomes of the other. A key driver of unfavorable TB treatment outcomes is suboptimal drug exposures. However, target drug concentrations of first-line TB drugs and cumulative exposure thresholds needed for optimal clinical outcomes, post-TB lung health, and prevention of emergence of resistance are not defined, particularly in programmatic settings. In our study entitled "investigating multiple PK and PD relationships for TB-HIV (impprove TB-HIV)," we will leverage the tuberculosis sentinel research network (TB SRN), a large global platform cohort study for coordinated observational TB research conducted among persons with pulmonary TB with and without HIV, within the international epidemiology databases to evaluate aids (iedea) consortium in six iedea regions, to conduct pharmacokinetic-pharmacodynamic (PK-PD) analyses, using a nested case-cohort design. We will measure individual PK via collection of dried blood spots (DBS), which are easy to collect, store, and ship, and cumulative drug exposure in hair, which reflects both adherence and PK. In aim 1 (PK-PD aim), we will examine the impact of TB drug PK and cumulative drug exposure on risk of unfavorable TB treatment outcomes (death, failure, recurrence) among individuals with pulmonary TB, with or without HIV. In aim 2 (PK-resistance aim), we will investigate the impact of drug exposures on emergence of TB drug resistance mutations. In aim 3 (PK-lung health aim), we will evaluate the association between anti-TB drug exposures and post-TB lung disease and longitudinal lung health. Thus, the impprove study aims to elucidate the relationships between drug exposures and unfavorable TB treatment outcomes, poor lung health, and resistance under field conditions, in a large multinational patient population, taking into account HIV status and other factors known to affect these outcomes. The goal is to inform optimization of TB treatment (right dose, right patient) to improve clinically-important outcomes for patients.

Transactions

Action Obligated Date
Amendment -$34,490
Original award $817,252

Subawards

Subrecipient Amount Awarded
Trustees Of Indiana University Investigating Multiple PK and PD Relationships for TB-HIV (IMPPRove TB-HIV) $51,826
Albert Einstein College Of Medicine Investigating Multiple PK and PD Relationships for TB-HIV (IMPPRove TB-HIV) R56 $43,710
The Trustees Of Columbia University In The City Of New York Investigating Multiple PK and PD Relationships for TB-HIV (IMPPRove TB-HIV) $40,855
Duke University $32,247
The Regents Of The University Of California. San Francisco $24,288
The Johns Hopkins University $258,068
Trustees Of Indiana University $51,826

Quick answers

Who received award R56AI174911?

R56AI174911 was awarded to Vanderbilt University Medical Center by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 21, 2023.

How much is award R56AI174911 worth?

$782,762 has been obligated on R56AI174911.

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