HIV continues to be one of the biggest problems for the global public health. The African region is one of the most affected, accounting for almost two thirds of the new infections. Many of them are retroviral medications and multi-therapies aiming to stop the viral replication and maintaining immunological stability, which fail to guarantee the quality of life or enhance the patient's immunity Ozone has biological properties, among which the antimicrobial and modulatory effect on the immune response is highlighted, which makes it possible to use it in a complementary way for the treatment of these patients. We conducted the present study in which the effect of the ozone therapy administered systemically (blood route) is analyzed. We have studied 32 patients to whom we applied Major Autohemotherapy with a protocol of 15 sessions and maintenance every 15 days at 50 µg/ml of concentration; the initial dose was 4,000 µg/mlup to 12,000 µg/ml We indicated viral load, CD4 and CD8 counts before and at the end of therapy. The results showed a significant decrease in viral load to undetectable values and an increase of CD4 and CD8 at the end of the 15 sessions, being maintained at 2 years of treatment, thus achieving a permanent activation of the immune system and improving the quality of life of these patients. Key words: Ozone therapy, HIV-AIDS, Immune Response, Major Autohemotherapy