Human immunodeficiency virus (HIV) infection remains one of the most acute problems of modern medicine. Tuberculosis is known as the leading cause of death among the opportunistic infections in HIV-positive people; moreover, TB is also known as resulting in one of three deaths associated with acquired immunodeficiency syndrome. It should be stressed the TB course against the background of HIV infection demonstrates the atypical characteristics, nonspecific clinical symptoms with increasing frequency of extrapulmonary lesions, minimal radiological manifestations, low frequency of the pathogen excretion, and rapid course of the disease. In recent years, researchers around the world have paid considerable attention to studying the effects of genetic variation of genes on the course of infectious diseases in humans, including HIV and tuberculosis, and in particular, to investigating Tool-receptors, innate immune system receptors, which interact with pathogens and stimulate effector mechanisms of innate immunity. The objective of this study is to determine the prevalence and evaluate the features of the TB course before and during the antiretroviral therapy, considering the carriage of the 299Gly allele of the TLR4 gene. To assess the manifestations, clarify the clinical characteristics of the disease in the dynamics before and during the antiretroviral therapy, a retrospective cohort examination of 181 HIV-positive patients before and after the therapy was carried out. The study has demonstrated that, despite the virological and immunological effectiveness of the treatment, the TB detection in HIV-infected patients taking antiretroviral therapy remained almost constant compared to the period before antiretroviral therapy (17.0% vs. 14.9%, > 0.05). Analysis of genotypes of the TLR4 gene showed that during the observation period before antiretroviral therapy in patients with the 299Gly allele there was a 6.3-fold higher risk of developing of disseminated TB forms (OR = 6.29 [95% 1.20-32.99], p = 0.044), compared with carriers of Asp299Asp genotype. In HIV-infected patients with the 299Gly allele of the TLR4 gene on the background of antiretroviral therapy, the risk of TB development is 3.4 times higher (p = 0.008) than in carriers of its homozygous genotype.