Factors Mediating Gut Microbiota Dysbiosis and Metabolic Disease in HIV Patients.

This is a prospective cohort and cross-sectional case-control study. Study participation will
last up to 2 months and 93 participants will be enrolled. Participants will be evaluated for
lipodystrophy, asked to complete food & gastrointestinal symptoms questionnaires and provide
stool samples. A subset of participants will be asked to have a flexible sigmoidoscopy
(mucosal biopsy).

Cohort A will consist of 93 participants:

Cohort A1: ART (Antiretroviral therapy) -treated HIV-infected individuals with lipodystrophy
(n=35) Cohort A2: ART-treated HIV-infected individuals without lipodystrophy (n=18) Cohort
A3: HIV-1 infected individuals naïve to ART (n=20) Cohort A4: HIV-1 seronegative individuals
who are at a high risk for infection (n=20)

Cohort B will be a selected subset of subjects from Cohort A:

Cohort B1: ART-treated HIV-infected individuals with HIV-associated dysbiosis (n=10) Cohort
B2: ART-treated HIV-infected individuals without HIV-associated dysbiosis (n=10)

Inclusion Criteria:

- Men and women; 18 years to 65 years (All Cohorts)

- Subjects with chronic HIV-1 Infection defined as a positive ELISA confirmed by a
positive Western Blot or plasma HIV-1 RNA level >1,000 copies/mL at any time in the
past. (Cohorts A1, A2 & A3)

- HIV-1 seronegative (Cohort A4)

- Either with or without lipodystrophy (to be assessed at Visit 1)

- Body mass index (BMI) between 21-29 mg/kg2 and weight stable for at least 3 months
(All Cohorts)

- Antiretroviral therapy (ART) naïve (Cohort A3): <10 days of ART treatment at any time
prior to Visit 1 or previously on ART but off treatment for the previous 6 months
prior to Visit 1

- Long-term ART (Cohort A1 & A2): Must be on same antiretroviral treatment and have a
plasma HIV-1 RNA <25 copies/mL for 3-6 months prior to Visit 1.Liver function tests
not greater than 2x normal, normal kidney and thyroid function. Fasting glucose must
be <110 mg/dl

- Liver function tests not greater than 2x normal, normal kidney and thyroid function.
Fasting glucose must be <110 mg/dl

- ART-treated individuals whose microbiota resembles those with untreated HIV infection
and ART-treated individuals whose microbiota resembles the HIV-negative control cohort
(equal numbers with and without lipodystrophy).(Cohort B; a subset of Cohort A)

Exclusion Criteria:

- Gastrointestinal disease such as inflammatory bowel disease, Clostridium difficile
colitis or celiac sprue.

- history of bowel resection, bleeding disorder, history of hyperglycemia, treated with
high-dose glucocorticoid therapy or alpha-interferon in past year Current use of
anticoagulant therapy

- Daily use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) with inability to
withhold drug for 7 days before and after a rectosigmoid biopsy procedure.

- Used antibiotics within the prior three months

- Pregnancy

- Current use of proton pump inhibitors and H2-blockers

- Active opportunistic or other chronic infection, such as hepatitis B or C or an active
malignancy

- Patient inability to participate in the study, such as inability to undergo
venipuncture, completion of questionnaire or mucosal biopsy (if selected) procedures
that form part of the inclusion/exclusion criteria or part of the outcome measure.