Coinfection of HIV and multidrug-resistant tuberculosis (MDR-TB) presents significant challenges in terms of the treatment and prognosis of tuberculosis, leading to complexities in managing the disease and impacting the overall outcome for TB patients. This study presents a remarkable case of a patient with MDR-TB and HIV coinfection who survived for over 8 years, despite poor treatment adherence and comorbidities. Whole genome sequencing (WGS) of the infecting Mycobacterium tuberculosis (Mtb) strain revealed a unique genomic deletion, spanning 18 genes, including key genes involved in hypoxia response, intracellular survival, immunodominant antigens, and dormancy. This deletion, that we have called "Del-X," potentially exerts a profound influence on the bacterial physiology and its virulence. Only few similar deletions were detected in other non-related Mtb genomes worldwide. In vivo evolution analysis identified drug resistance and metabolic adaptation mutations and their temporal dynamics during the patient's treatment course.
Keywords: HspX; Mycobacterium tuberculosis (MTB); acquired immunodeficiency syndrome (AIDS); dormancy; human immunodeficiency virus (HIV); in vivo evolution; multidrug-resistant tuberculosis (MDR-TB); whole genome sequencing (WGS).
Copyright © 2023 Rubinstein, Makhon, Losev, Valenci, Gatt, Margalit, Fass, Kutikov, Murik, Zeevi, Savyon, Tau, Kaidar Shwartz, Dveyrin, Rorman and Nissan.