Fecal Microbiota Transplantation in HIV

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.

Inclusion Criteria:

1. HIV infected men and women 18-75 years of age.

2. On continuous anti-retroviral therapy for at least one year.

3. Undetectable viral load for at least one year.

4. Written informed consent obtained from the subject and ability of the subject to
comply with the requirements of the study.

Exclusion Criteria:

1. CD4 T cell count less than 200 cells/mL.

2. Recent antibiotic use in the last 3 months.

3. Pregnant, breastfeeding, or unwilling to practice birth control during participation
in the study.

4. Presence of a condition or abnormality that in the opinion of the Investigator would
compromise the safety of the patient or the quality of the data.

5. Active GI symptoms: inflammatory bowel disease, abdominal pain, hematochezia, or
other symptoms requiring medical evaluation and intervention.

6. Recent hospitalization or acute medical condition within preceding three months.

7. Severe comorbidities: cirrhosis, coagulopathy, heart failure, renal failure, and
respiratory failure.

8. Testing positive for any of the stool screening test: Clostridium difficile toxin by
PCR, routine bacterial culture for enteric pathogens (E coli, Salmonella, Shigella,
Yersinia, Campylobacter), culture for Vibrio, fecal Giardia antigen, fecal
Cryptosporidium antigen, acid-fast stain for Cyclospora and Isospora, ova and
parasites, stool for Rotavirus via EIA.

9. History of anaphylaxis.

10. Major immunosuppressive medications (e.g., calcineurin inhibitors, exogenous
glucocorticoids, biological agents, etc.) or systemic antineoplastic agents.