# Predictors of Resistance Emergence Evaluation in MDR-TB Patients on Treatment (PREEMPT)

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $905,202

## Abstract

Abstract
 Tuberculosis (TB) is a leading causes of global mortality. Nearly one-third of the world's population is
infected with M. tuberculosis, an estimated 10.4 million new cases of TB develop annually, and 1.4 million
persons die from the disease. The HIV pandemic and TB/HIV co-infection have fueled escalating TB incidence,
and complicated TB management and control. The emergence of multi-drug resistant (MDR) and extensively
drug resistant (XDR) TB has exacerbated the threat to public health and created a renewed sense of urgency
to control the disease. Treatment of MDR-TB leads to emergence of additional drug resistance in 6-20% of
patients on treatment. We propose to investigate the causes of emergence of mycobacterial drug resistance in
an observational cohort study, the Predictors of Resistance Emergence Evaluation in MDR-TB Patients on
Treatment (PREEMPT) Study. This proposal takes advantage of two existing TB cohort studies in India and
Brazil (Regional Prospective Observational Research for Tuberculosis: RePORT India and RePORT Brazil),
co-funded by NIAID and the Indian and Brazilian governments, respectively.
 In the PREEMPT study, we will enroll 400 patients with MDR-TB in India and Brazil over a 24-month
period and follow them prospectively for 3 years. The proposal has the following Specific Aims:
 Aim 1: To determine whether low serum antimycobacterial drug concentrations contribute to
the emergence of drug resistance in MDR TB patients, and whether HIV seropositivity is a risk factor
for low serum drug concentrations and/or the emergence of resistance.
 Aim 2: To determine the contribution of increased DNA mutation (caused either by an intrinsic
property of the M. tuberculosis strain or by FQ treatment) to clinical emergence of drug resistance in
patient isolates.
 Aim 3: To determine whether mutations responsible for drug resistance can be detected early
during treatment, when an intervention to prevent XDR-TB might be possible.
 This proposal builds on an existing TB research framework to study mechanisms of emergence of TB
drug resistance during MDR-TB treatment. It is very likely that similar mechanisms will explain emergence of
TB drug resistance during treatment for drug-susceptible TB. Each of the proposed mechanisms of emergence
of resistance that we will investigate has direct implications for new regimen designs, new drug administration
algorithms and new drug susceptibility monitoring strategies that could prevent emergence of resistance in
patients with TB with and without HIV.

## Key facts

- **NIH application ID:** 10212930
- **Project number:** 5R01AI134430-05
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Charles Robert Horsburgh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $905,202
- **Award type:** 5
- **Project period:** 2017-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212930

## Citation

> US National Institutes of Health, RePORTER application 10212930, Predictors of Resistance Emergence Evaluation in MDR-TB Patients on Treatment (PREEMPT) (5R01AI134430-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10212930. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*