As tuberculosis disease is the most prevalent opportunistic entity in patients immunocompromised by the human immunodeficiency virus (HIV) and the main cause of mortality, it is necessary to establish preventive measures that reduce its potential appearance. The problem arises due to the low sensitivity of the diagnostic tests used for the diagnosis of latent tuberculosis infection (ILTB) in patients with CD4 counts lower than 200, a diagnosis required for the initiation of prophylaxis. After conducting an observational, analytical, retrospective cohort study, the aim is to establish the protective effect of prophylactic isoniazid in patients with low CD4 counts and absence of ILTB in diagnostic confirmation. The exposed cohort (n: 264) was made up of patients who received prophylactic therapy while those who were not offered preventive therapy made up the unexposed cohort (n: 198). The follow-up was carried out for 30 months, the outcome variable being the presence of active tuberculosis disease. The present investigation deals with a retrospective cohort study in patients with HIV and CD4 counts below 200, providing prophylactic isoniazid to one of the groups and searching during follow-up for the presence of tuberculosis disease (TE) as a complication 6 Out of a total of 462 patients who were evaluated in both cohorts (264 in the prophylaxis group). ET was documented in 6.8% of patients exposed to prophylaxis and in 19% of those who did not receive it RR: 0.29 CI 0.29 - 0.54 p 0.000 As ET is the main cause of morbidity and mortality in patients with HIV, preventive measures such as the prescription of isoniazid due to its clear benefit and without establishing the diagnosis of ILTB due to the low sensitivity of the diagnostic tests.