Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV.

BACKGROUND: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis. METHODS: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured. RESULTS: Median age at week 0 was 39 years, CD4(+) T cell count 496 cells/mm(3), HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. α diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest α diversity at week 0. At week 26, α diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low α diversity that improved between weeks 0 and 6 with a shift in distribution. CONCLUSIONS: Weekly FMT was safe and well-tolerated. α diversity increased in participants with the lowest baseline α diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560.