Fecal Microbiota Transplantation in HIV
Condition: HIV
Study type: Interventional
Phase: Phase 1

Summary: 
      Even in individuals treated for HIV, chronic immune activation persists and is associated
      with increased cardiovascular disease, liver disease, and mortality. HIV-infected individuals
      have imbalances in the community of intestinal microbes which is thought to contribute to
      increased and persistent inflammation. The purpose of this study is to examine the safety and
      durability of fecal microbiota transplant (FMT), the transfer of the bacterial community in
      stool from a healthy donor, in HIV+ individuals on anti-retroviral therapy. The study will
      also measure the effects of FMT on immune activation and inflammatory biomarkers in
      anti-retroviral treated HIV+ individuals.
    

Detailed description: 
      Despite antiretroviral therapy (ART), chronic immune activation persists and is a major
      driver of HIV disease progression and mortality among HIV-infected individuals. Importantly,
      persistent inflammation is strongly associated with increased cardiovascular events,
      accelerated liver disease, impaired immunologic recovery (e.g. low CD4 count, low CD4 to CD8
      ratio), and mortality. Therefore, addressing persistent inflammation remains a major goal to
      restoring health in HIV-infected individuals.

      Novel therapeutic strategies to decrease immune activation in treated HIV infection are
      needed. Marked disruption of the gut microbial composition, or dysbiosis, is characteristic
      of HIV-infected individuals and persists despite long-term ART. Recent studies demonstrate
      that the relative degree of gut microbiome disruption positively correlates with inflammatory
      markers (IL-6, kynurenine to tryptophan ratio). Microbial dysbiosis and its inflammatory
      consequences may be an attractive target for interventions to decrease immune activation in
      HIV+ individuals.

      Fecal microbiome transplantation (FMT) has proven durable and successful as a therapeutic
      strategy against gut dysbiosis, such as in the treatment of recurrent Clostridium difficile
      infection, by restructuring the composition of the gut microbiome to resemble that of the
      healthy donor. FMT has an established record of safety with limited adverse effects, even in
      the context of immunocompromised and HIV-infected subjects. Donor selection and screening
      will be conducted by OpenBiome.

      The objective of this phase I clinical trial is to establish the safety and durability of FMT
      in HIV+ individuals. The microbiome of recipients will be analyzed up to 8 weeks post FMT for
      evidence of engraftment from the donor microbiome. We will further examine the effect of FMT
      on markers of immune activation and inflammation in ART treated HIV-infected individuals.
    

Intervention name(s): Fecal Microbiota
Intervention type(s): Drug
Intervention description(s): 300 mL of fecal suspension from a healthy donor will be delivered during colonoscopy
Other intervention name(s): stool transplant
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: inflammation; microbiome; immune activation; fecal microbiota transplantation; dysbiosis