The Effects of Recombinant Human Lactoferrin on Immune Activation and the Intestinal Microbiome Among Individuals with HIV Infection Receiving Antiretroviral Therapy

Alterations in the intestinal microbiome and loss of mucosal integrity are posited mechanisms contributing to inflammation during HIV disease. We conducted a randomized placebo-controlled cross-over clinical trial of human recombinant (rh)-lactoferrin, which modulates mucosal immunity interferes with lipopolysaccharide binding, among fifty-four HIV+ participants ≥40 years old with viral suppression. Outcomes were tolerability, safety, as well as inflammatory and immunologic measurements in blood that were compared within participants (during three month treatment with rh-lactoferrin vs. placebo) using longitudinal mixed models. The intestinal microbiome was analyzed among twelve participants. 46 participants completed ≥2 visits during both rh-lactoferrin and placebo study periods. Median age was 51 years, CD4+ count was 651 cells/mm3, and groups were similar across co-morbid risk factors. Adherence and adverse events did not differ between rh-lactoferrin and placebo treatment periods. There was no significant treatment effect of rh-lactoferrin vs. placebo on plasma interleukin-6 and D-dimer levels, nor on other measurements of inflammation, coagulation, mucosal integrity, monocyte activation, or T-cell activation. Intestinal microbiota diversity, phyla and family abundance demonstrated stability after rh-lactoferrin or placebo treatment. Oral administration of rh-lactoferrin was well tolerated and safe, but did not reduce inflammation and immune activation or alter the intestinal microbiome. Submission was done on behalf of Irini Sereti, Jason V. Baker and Ornella Sortino.