Although proven to be safe and efficacious in the treatment of sepsis, recombinant human (rh)-lactoferrin treatment in people living with HIV (PLWHIV) receiving antiretroviral therapy (ART) was not associated with significant improvements in inflammation or immune activation, nor with changes to intestinal microbiota, according to a study published in The Journal of Infectious Diseases.
This randomized, placebo-controlled, cross-over clinical trial (NCT01830595) was designed to evaluate the effect of rh-lactoferrin in PLWHIV who were aged 40 years or older, were on continuous treatment with ART, and had HIV RNA levels <200 copies/mL for at least 1 year prior to enrollment (N=54, 89% male, median age 51 years). The study included a 3-month treatment period where participants were randomly assigned either 1500mg of oral rh-lactoferrin or placebo, followed by a 2-4 month wash-out period, and then a 3-month treatment period where those previously assigned to rh-lactoferrin were given the placebo and those assigned the placebo were given rh-lactoferrin. Outcomes were inflammatory and immunologic measures (calculated using longitudinal mixed models), tolerability, and intestinal microbiome.
The rate of adverse events and adherence did not differ between patients who first received rh-lactoferrin then placebo (n=28) and patients who first received placebo followed by rh-lactoferrin (n=26). Although oral administration of rh-lactoferrin was shown to be safe, no significant effects were seen on markers of inflammation, such as levels of D-dimer or plasma interleukin-6. Researchers also noted that at both the Phylum and Family level, no significant effect on intestinal microbiota was noted after 3 months of treatment with either placebo or rh-lactoferrin; mucosal integrity, monocyte/T-cell activation also remained unaffected.
Limitations to this study included a small sample size, the choice of rh-lactoferrin preparation, a lack of assessments of mucosal tissue, limited characterization of intestinal microbiota, and suboptimal participant adherence.
Study investigators concluded that “rh-lactoferrin treatment among ART-treated PLWH[IV] did not result in significant changes to inflammation or immune activation within blood, nor to changes in the intestinal microbiota. Additional strategies to reduce inflammation by targeting intestinal dysbiosis and improving mucosal immunity are needed to improve the health of PLWH[IV].”
Sortino O, Huppler Hullsiek K, Richards E, et al. The effects of recombinant human lactoferrin on immune activation and the intestinal microbiome among people living with HIV receiving antiretroviral therapy [published online February 5, 2019]. J Infect Dis. doi: 10.1093/infdis/jiz042