Genetic polymorphisms and adverse reactions to antituberculosis therapy

Area of Science:

• Pharmacogenomics
• Infectious Diseases
• Clinical Pharmacology

Background:

• Tuberculosis (TB) remains a leading global infectious cause of death, particularly in low- and middle-income countries.
• Effective TB treatment necessitates prolonged, multi-drug regimens, increasing the risk of adverse drug reactions (ADRs).
• Multidrug-resistant TB necessitates new drug development, further complicating treatment strategies and ADR management.

Purpose of the Study:

• To review major treatment-limiting ADRs associated with TB drugs.
• To explore the current understanding of drug metabolism, ADR pathophysiology, and pharmacogenetic risk factors for TB drugs.
• To identify research gaps and implementation barriers for pharmacogenetic testing in TB treatment.

Main Methods:

• Literature review focusing on TB drug ADRs, pharmacology, and pharmacogenetics.
• Analysis of current knowledge on drug metabolic pathways and ADR pathophysiology.
• Identification of known pharmacogenetic risk alleles relevant to TB drug toxicity.

Main Results:

• Significant treatment-limiting ADRs exist for current and emerging TB drugs.
• Understanding of drug metabolism and ADR pathophysiology is advancing, revealing potential pharmacogenetic influences.
• Several pharmacogenetic risk alleles have been identified, but their clinical application in TB is minimal.

Conclusions:

• Pharmacogenetic testing holds promise for optimizing TB treatment regimens and preventing ADRs.
• Significant barriers hinder the clinical implementation of pharmacogenomics in TB care.
• Further research and strategic implementation are needed to leverage pharmacogenetics for improved TB patient outcomes.