This is a Phase IV, open label, observational study to compare the gastrointestinal tissue
concentrations, inflammatory response, and viral replication of two integrase-inhibitors,
raltegravir and dolutegravir, in HIV-infected volunteers who are virologically suppressed in
blood plasma. The study will be comprised of 20 HIV-infected volunteers who will be enrolled
equally into two groups. Group A will consist of 10 subjects receiving an antiretroviral
regimen of tenofovir, emtricitabine, and raltegravir, and Group B will consist of 10
subjects receiving an antiretroviral regimen of tenofovir, emtricitabine, and dolutegravir.
Participants will provide small pieces of tissue, or biopsies, which will be taken from
three distinct locations of the large intestine during a colonoscopy procedure. These
biopsies will be used to measure the amount of raltegravir or dolutegravir, HIV virus, and
inflammatory markers present in the gastrointestinal tract.
- 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
- 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
- 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,
- 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
- 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.