The Effects of High-Dose Probiotic Supplementation on Immune Activation and Neurocognitive Disorders in People Living with HIV Undergoing Successful Antiretroviral Treatment: The Procog Study.

Background: The prevalence of HIV-associated neurocognitive disorders (HAND) remains high despite antiretroviral treatment (ART). Changes in gut microbiota and persistent immune activation have been suggested as possible causes, while the role of probiotic supplementation remains controversial.

Methods: We included subjects with mild HAND and successful ART. They were randomized to receive either 6 months of high-dose probiotic supplementation or to continue with only ART. Immune activation markers and neuropsychological testing were performed at baseline and the end of follow-up. Neuropsychological testing assessed learning, episodic memory, attention/concentration, executive functions, language, information processing speed, and motor skills. Z- and T-scores were calculated for all domains but motor skills, allowing the measurement of the global deficit score (GDS). The trajectories of neuropsychological performances and immune activation markers were compared between groups.

Results: From September 2020 to July 2021, 31 PWHs were included (median age 62, 73% men, CD4 744 cc/mm³), and 28 completed the 6-month follow-up. The characteristics of the subjects and their neuropsychological performance at baseline in the two groups were similar. At the end of follow-up, probiotics did not have any impact on immune activation markers, while they were associated with better improvement in GDS (T-score 0.0 in controls vs. -0.3 in probiotics, p = 0.048) and the attention/concentration test (Z-score 0.4 in controls vs. 1.2 in probiotics, p = 0.035).

Conclusions: Oral supplementation with high-dose probiotics for 6 months did not affect systemic immune activation but was associated with improved neurocognitive performance, suggesting benefits from probiotic supplementation for mild HAND.