Comparison of Virologic and Immunologic Responses to Raltegravir and Dolutegravir in the Gastrointestinal Tract of HIV-Positive Adults

Purpose: To compare virologic and immunologic responses to raltegravir and dolutegravir in
the gastrointestinal tract of HIV-positive men and women

Participants: Twenty HIV-infected volunteers will be enrolled equally into two groups. Group
A will consist of subjects receiving an antiretroviral regimen of raltegravir, tenofovir, and
emtricitabine and Group B will consist of subjects receiving an antiretroviral regimen of
dolutegravir, tenofovir, and emtricitabine.

Procedures (methods): This is a Phase IV, open label study to compare the gastrointestinal
tissue concentrations, cytokine response, and viral replication in gut-associated lymphoid
tissue of two integrase-inhibitors in HIV-infected volunteers who are virologically
suppressed in blood plasma. Subjects will undergo an observed bowel preparation, followed by
a colonoscopy in which tissue will be obtained by a board-certified gastroenterologist from
the terminal ileum/ascending colon, splenic flexture, and rectum/sigmoid colon. Blood plasma
will be collected immediately prior to collection of tissue samples.

Inclusion Criteria:

- Healthy HIV-positive adults aged 18-65, inclusive on the date of screening, with
documentation of at least one positive HIV test. Healthy is defined as no clinically
relevant abnormalities that would interfere with the interpretation of results, or
pose unnecessary risk onto volunteers due to study procedures.

- Receiving an antiretroviral regimen containing tenofovir+emtricitabine with
raltegravir (Group A) or dolutegravir (Group B) for > 3 months, with blood plasma HIV
RNA < 50copies/mL for at least 4 weeks, or a 2 log decrease in baseline blood plasma
HIV RNA.

- Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the trial.

- Documentation of at least 80% adherence to antiretroviral regimen, through clinician
or self-report, with no missed doses in the 3 days prior to the inpatient visit.

- Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other trial procedures.

- Women of childbearing potential must be utilizing at least one acceptable form of
birth control.

Exclusion Criteria:

- Evidence or history of clinically significant hematological, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurologic
disease that would pose unnecessary risk or interfere with study results. Subjects
will be excluded for any condition that would increase risk from sedation, endoscopy,
or biopsy.

- Subjects with a history of having a gastrectomy, colostomy, ileostomy, or any other
clinically significant procedure altering the gastrointestinal tract, or any condition
possibly affecting drug absorption.

- Subjects with inflammatory bowel diseases (ulcerative colitis or Crohn's disease).

- Female subjects who are currently pregnant or breastfeeding, or planning to become
pregnant during the study period.

- Subjects who are unwilling to refrain from insertion of medical/recreation devices and
products into the rectum, and from receptive anal intercourse, for 72 hours before
inpatient study visit and through 7 days after the last biopsy unless instructed
otherwise by the investigators.

- A positive urine drug screen.

- Untreated rectal sexually transmitted infection at screening.

- Treatment with an investigational drug within 2 months preceding study enrollment.

- Participated in a gastrointestinal biopsy study in the 3 months preceding study
enrollment.

- Participants with a history of clotting or bleeding disorders.

- Participants with a history of abnormal reaction to, or complication from, conscious
sedation or anesthesia

- Subjects who are unwilling or unable to comply with the following dietary restrictions
in regard to study procedures, including a clear liquid diet during bowel preparation
and a period of NPO (nil per os) prior to the colonoscopy. While confined, the total
daily nutritional composition will be 50% carbohydrate, 15% protein, and 35% fat. The
daily caloric intake should not exceed 3200kcal.

- Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which in
the opinion of the clinician represents a contraindication to biopsy (including but
not limited to presence of any unresolved injury, infectious or inflammatory condition
of the local mucosa, and presence of symptomatic external hemorrhoids).

- Any other reason or condition that in the judgment of the investigators would make
participation in the study unsafe, complicate interpretation of study outcome data, or
otherwise interfere with achieving the study objectives.