AbstractIntroductionProbiotics are live microorganisms that, when administered in appropriate colonies, can delay the destruction of the immune system and contribute to the maintenance of immunity in HIV patients. Probiotics play an important role in stimulating natural killer T cells, strengthening the functional gut barrier, and reducing systemic inflammation.MethodsThis study was a randomized double‐blind clinical trial involving 30 patients treated with antiretroviral therapy who had experienced immunological failure despite HIV viral suppression. Patients were divided into two equal groups of 15, group (B) received two probiotic capsules daily with a colony count of 10⁹ CFU per capsule containing seven strains, after 3 months they were examined for CD4+counts by flow cytometry, and after a 1‐month washout period the participants who had received probiotics were switched to placebo, and the participants who had received placebo were given probiotics for 3 months, and they were examined for CD4+counts 7 months after the start of the study.ResultsIn the first group (A), administration of the placebo resulted in a decrease in CD4 count in the first 3 months (from 202.21 to 181.79,pvalue < .001), which may be due to the natural history of the disease. After probiotics administration, CD4 count increased significantly (from 181.79 to 243.86,pvalue < .001). Overall, after 7 months of study, there was a significant increase in the mean CD count from 202.21 to 243.86 (pvalue < .001). In the second group (B), the administration of probiotics in the first 3 months of the study resulted in a significant increase in the mean CD4 count (from 126.45 to 175.73,pvalue < .001). Termination of treatment with probiotics resulted in a significant decrease (from 175.73 to 138.9,pvalue < .001) but overall the CD4 count at the end of the study was significantly higher than at baseline (pvalue < .001).