Time for Isoniazid Pharmacogenomic-Guided Therapy of Tuberculosis Based on NAT2 Acetylation Profiles in India

Abstract

Tuberculosis (TB), caused by a bacterial pathogen Mycobacterium tuberculosis, is a highly contagious infectious disease. India ranks top in TB burden among other countries in the world. The current treatment of TB in India includes isoniazid (INH) as the first-line drug, based on the "one dose fits all'' concept. It is widely known that INH is not equally tolerated by all patients, as the metabolization process of INH is highly dependent on the acetylation profile of an individual based on the pharmacogenomic profile of the N-acetyltransferase (NAT2) gene. Also, several experimental studies in several TB endemic countries have established that redosing of INH based on genetic profiles of TB patients of the NAT2 can help in effective TB treatment and minimize adverse drug reactions (ADRs). Moreover, acetylation phenotype-based INH dosing has been shown to be cost-effective as well as successful in terms of treatment outcomes and the increase in the quality of life of the patients. Considering a genetically heterogenous population with high vulnerability to TB, we here argue that India could lead in establishing a pharmacogenomic-guided therapy (PGT) under the INH-NAT2 model. With such an approach, not only could an innovative step towards 'End-TB' by the year 2025 be taken but a personalized medicine approach for TB treatment be initiated in India, particularly in tribal communities.