A randomized, blinded, placebo-controlled trial of De Simone formulation probiotic during HIV-associated suboptimal CD4+ T cell recovery.

OBJECTIVE To assess whether probiotic supplementation may reduce disease-linked systemic immune activation in people living with HIV with the immunologic non-responder (INR) phenotype. DESIGN Phase 2b, randomized, double-blind, placebo-controlled pilot trial. METHODS HIV-positive individuals with blood CD4+ T cell counts <350/mm3 despite viral suppression were randomized 2:1 to receive De Simone Formulation Probiotic (DSFP; "Visbiome" commercially) or placebo for 48 weeks; target enrolment was 36 patients. The primary endpoint was change in blood CD8+ T cell co-expression of HLA-DR and CD38 ("CD8 activation"). Secondary endpoints included biomarkers of inflammation, immune reconstitution, bacterial translocation, and gut permeability. Adjusted linear regression and linear mixed methods regression evaluated the differences between study arms from baseline to week 48. Study monitoring was done by the CIHR Canadian HIV Trials Network Data Safety Monitoring Committee. RESULTS Nineteen patients received DSFP, while 10 received placebo. One probiotic-arm patient withdrew early. Blood CD8 activation increased 0.82 percentage points (pp) in the probiotic arm (95% confidence interval [CI];-1.23,2.87;) and decreased by 2.06pp in the placebo arm (-4.81,0.70; between arms p=0.097). CD4+ T cell activation (%HLA-DR+) decreased in the placebo arm (-3.79pp [-7.32,-0.26]) but increased in the probiotic arm (1.64 [-0.98,4.26]; between arms p=0.018). No differences were observed in plasma or urine biomarkers of inflammation or microbial translocation. CONCLUSIONS Blood immune activation markers in INR individuals on effective ART were not reduced by supplementation with DSFP; CD4+ T cell activation may have been increased.