Mycobacterium tuberculosis (MTB) clinical strains are relatively varied at the genome level. This in-silico study analyzed genomic differences between MTB isolates from the blood and lungs of TB-HIV positive cohorts in Uganda. The hypothesis was that isolates from the blood have distinct SNPs and INDELs that make them better survivors. Twenty-four MTB-blood and -lung sequences were aligned against the H37Rv reference genome and analyzed using BWA-MEM, IGV, SAMtools, Forebays, and SnpEff. Comparative analysis revealed that MTB-blood isolates had 11 virulence genes with distinctive non-synonymous SNPs involved in increasing colony-forming units, lowering host survival, enhancing tissue pathology, and allowing for human host persistence. The majority of INDELs were found in non-virulence genes, with the remainder in both MTB-blood and -lung sequences. The study suggests that MTB-blood isolates have distinctive SNPs that explain their capacity to persist outside of the lungs. However, further research is needed to understand the significance of these SNPs in the pathogenesis of MTB