Background:  HIV-1 infection is characterized by progressive deterioration of the immune system manifested by depletion of CD4⁺ T cells, chronic immune activation, and altered effector functions. In contrast to the hyper activation of T cells, the cytolytic activity of natural killer (NK) cells from viremic patients is reduced compared to non-infected individuals, HAART-treated aviremic patients, or long-term non-progressors (LTNP). Emphasizing the role and deterioration of the gastrointestinal tract and acknowledging the relationship between nutritional intervention and immune function, we hypothesized that prebiotic intervention could induce beneficial immunologic changes in HIV infection.
Methods:  In a double-blind, placebo-controlled pilot study (COPA-trial), 57 HAART-naive HIV⁺ adults (baseline median (range) of CD4⁺ T lymphocyte count 451 (300 to 1080) cells/µL and HIV RNA levels 11014 (49 to 196524) copies/mL) were randomized to receive either placebo (maltodextrin) or a specific mixture of prebiotic oligosaccharides (15 g or 30 g/day) consisting of galactooligosaccharides (GOS), long-chain fructooligosaccharides (lcFOS), and acidic oligosaccharides (AOS) for 12 weeks. Fluorescence-activated cell sorting (FACS) analyses were performed on fresh peripheral blood mononuclear cells (PBMC). CD4⁺/CD25⁺, CD4⁺/CD25⁺⁺/Fox-p3⁺ and CD14⁺/B7-H1⁺ as well as spontaneous cytolytic activity at effector:target ratios of 50:1, 25:1 and 12.5:1 were analyzed. Results obtained at week 12 compared to baseline are reported and statistically analyzed using Mann Whitney or ANOVA.
Results:  A dose-dependent reduction of activated CD4⁺/CD25⁺ T cells was detected in groups receiving GOS/lcFOS/AOS (p = 0.09 (15 g/day) and p <0.01 (30 g/day). The percentage of regulatory T cells (Fox-p3⁺) or CD14⁺/B7-H1⁺ expressing monocytes were comparable between the groups and did not change over time. In contrast, cytolytic activity of natural killer (NK) cells was improved significantly in the group receiving GOS/lcFOS/AOS (15 g/day) at each effector:target ratio with 3.44- to 4.25-fold (p <0.002) and with 1.92- to 2.15-fold in patients receiving 30 g/day (NS).
Conclusions:  This study shows a promising role for prebiotic intervention in early HIV infection. A short cycle of treatment with oligosaccharides in HAART-naive HIV⁺patients results in an improvement of NK cell cytolytic activity and reduction of hyper-immune activation. These data warrant further investigation towards the effect of prolonged prebiotic intervention on the gastrointestinal tract, disease progression and clinical outcome in HIV infection.