The pandemic of HIV infection, tuberculosis and sexually transmitted infections is characterized by the formation of multicomorbid conditions. The coexistence of pathogenetically interrelated and interdependent epidemics of different infections developing in an environment conducive to their spread is described by the term “syndemia”, which can be observed in relation to HIV infection, tuberculosis and syphilis. On the example of clinical observation, the difficulties of managing a rare case of tuberculosis and syphilis against a background of HIV infection are described. Clinical, radiological and laboratory features of this mixed infection are considered. The role of radiological diagnostic methods for the detection of HIV-associated tuberculosis in case of negative results of bacteriological tests are substantiated. The progression of the specific process, opportunistic infections and side effects on combination therapy with severe immunosuppression make the treatment of this category of patients extremely difficult. Due to the increase in the spread of tuberculosis and syphilis among HIV-infected people, close attention should be paid to screening patients at risk of infection. Introduction of effective preventive and anti-epidemic measures is also required. The outlined phased diagnostic process is of practical importance for specialists of various fields.