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• Despite advanced diagnostic approaches for Mtb, sub-Saharan Africa with high HIV and TB co-infections continues to suffer. • Epigenetic mechanisms can be used in such co-infections to bypass host's immune responses. • Epigenetic modifications in the expression profile of different genes in MDR TB-HIV co-infection patients was studied. • Modulation in gene expression can be used for diagnostic, drug and vaccine development in MDR TB-HIV co-infection patients. Background: Mycobacterium tuberculosis (Mtb) is an airborne pathogenic microorganism that causes tuberculosis (TB). This pathogen invades lung tissues causing pulmonary infections and disseminates into other host organs. The Bacillus Calmette-Guérin (BCG) vaccine is employed to provide immune protection against TB; however, its efficacy is dependent on the age, immune status and geographic location of vaccinated individuals. Advanced diagnostic approaches such as GeneXpert MTB/RIF® and line probe assays (LPAs) have allowed rapid detection of drug-resistant, multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains. However, in sub-Saharan Africa, public and private health institutions are further burdened by the high prevalence of Human Immunodeficiency Virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) and TB co-infections across different age groups. Epigenetic mechanisms have been widely exploited by Mtb and HIV to bypass the host's innate and adaptive immune responses, leading to microbial proliferation and disease manifestation. In the current study, we investigated the impact of epigenetic mechanisms in regulating target gene expression in healthy and patients co-infected with MDR TB-HIV. [ABSTRACT FROM AUTHOR]