Immune effects ofLactobacillus caseiShirota in treated HIV-infected patients with poor CD4+T-cell recovery

Background: HIV infection leads to depletion of intestinal CD4+ T cells, mucosal barrier dysfunction, increased gut permeability and microbial translocation even among patients on suppressive ART. Previous studies suggest probiotics may help restore intestinal function. Methods: In this double-blind, placebo-controlled pilot study, we enrolled HIV-infected patients on suppressive ART with poor CD4+ recovery to address the effect of daily oral use ofLactobacillus caseiShirota (LcS) on CD4+ T-cell count and CD4+/CD8+ ratio at 6 and 12 weeks after treatment initiation; immune activation and intestinal microbiome composition were addressed as secondary outcomes. Results: From January 2015 to July 2016, 48 patients were randomized (1 : 1) to active intervention or placebo. Groups had comparable demographic and clinical characteristics; only CD4+ T-cell nadir was statistically different between groups. All participants were virologically suppressed under ART. At week 6, the increment in CD4+ T-cell count was 17 cells/mu l [interquartile range (IQR) -33 to 74] in the active intervention arm and 4 cells/mu l (IQR -43 to 51) in the placebo arm (P = 0.291); at week 12, the change in CD4+ T-cell count was 8 cells//mu l (IQR -30 to 70) in the active arm and 10 cells//mu l (IQR -50 to 33) among participants allocated to placebo (P = 0.495). Median change in CD4+/CD8+ ratio at week 6 compared with baseline was 0 (IQR -0.04 to 0.05) in the active intervention arm and -0.01 in the placebo arm (IQR -0.06 to 0.03;P = 0.671). At week 12, the change in CD4+/CD8+ ratio was higher in the active product group compared with placebo (respectively 0.07 and 0.01), but this difference failed to reach statistical significance (P = 0.171). We found no significant effects of LcS on immune activation markers, CD4+ and CD8+ subpopulations, sCD14 levels or NK cells at week 12. Finally, we found no statistically significant differences between groups in the change of enteric microbiome at week 12. Conclusion: In this pilot study, we found no statistically significant effect of LcS probiotic on CD4+ T-cell counts, CD4+/CD8+ ratio, immune activation or intestinal microbiome among HIV-infected patients on suppressive ART with poor CD4+ recovery.