Microbicides are topical medicines that can prevent infection by Human Immunodeficiency Virus (HIV). Microbicide medicine has yet to be studied in adolescents, a key group that is becoming infected with HIV all over the world. From past research, we know that at different ages people experience age-related changes in their bodies that can cause differences in how they process medications. In this study, gut tissue samples (or gut biopsies) from 12 HIV-negative volunteers will be collected. These pieces of tissue will be infected with HIV in the laboratory to develop a model that can be used to test certain drugs against the HIV infection. We can use this tissue to test a drug called tenofovir against HIV infection. We will determine whether this drug can decrease HIV infection in the gut biopsies. In this study, we will also measure HIV levels and the levels of tenofovir in gut and blood samples in 12 people who are already taking this drug. This information can determine whether levels of drug found in the gut can protect it from HIV. The results can be compared to other age groups of adolescents and adults. Subjects will undergo a common procedure called a lower endoscopy (this can be a colonoscopy or a flexible sigmoidoscopy) to obtain gut biopsy samples.

The central hypothesis is that tissue drug profiles of tenofovir (TFV) and its active component, tenofovir disoproxil fumarate (TDF), and tissue infectibility vary between younger (10-14 years old) versus older adolescents (18-21 years old), and that both differ from adults (>21 years). Specifically, younger HIV positive adolescents will have lower levels of tissue tenofovir compared to older HIV positive adolescents and adults in an age-dependent manner. Additionally, biopsies from younger HIV negative adolescents will have: 1) higher rates of infection compared to biopsies from older HIV negative adolescents infected with a lower dose of virus; and 2) lower percent suppression of tissue infectivity compared to biopsies from older HIV negative adolescents using low dose tenofovir.

Inclusion Criteria:

1. Age >/= 10 years and </= 14 years and age </= 18 years and </= 21 years.

2. Willing and able to communicate in English.

3. Willing and able to provide written informed consent or assent to take part in the study (where required, parent/guardian must provide consent).

4. Willing and able to provide adequate information for locator purposes.

5. Understand and agree to local sexually transmitted infections (STI) reporting requirements.

6. HIV-negative or -positive as documented in prior serologic testing or per report, and willing to undergo repeat HIV testing.

7. Willing and able to not take aspirin, any aspirin containing medications, or non-steroidal anti-inflammatory drugs for at least 72 hours before and 72 hours after flexible sigmoidoscopy.

8. All female patients of childbearing potential (post-menarche) must be willing to undergo urine pregnancy testing at screening.

9. Must be in general good health, including normal renal function.

10. Subjects <18 years old must be scheduled for a clinically indicated colonoscopy or flexible sigmoidoscopy with biopsies.

11. HIV-positive participants only (Aim 1):

    • Must have recent HIV polymerase chain reaction (PCR) documented in the last 6-12 months by verbal report
    • Must have tenofovir in chronic cART regimen (>/= 1 month).
    • Be reportedly compliant.
    • CD4 T cells >250/cmm

Exclusion Criteria:

1. Known history of inflammatory bowel disease.

2. 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, inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids).

3. Evidence of any known enteric infection at the time of study visit.

4. Participant-reported symptoms and/or clinical or laboratory diagnosis of active and symptomatic rectal infection (gonorrhea, Chlamydia, syphilis, clinically active perineal HSV).

   • Note: Allow one re-screening after documented treatment (30 days) in cases of gonorrhea/chlamydia (GC/CT) identified at screening.

5. Pregnancy.

6. Subjects with other poorly controlled medical conditions (e.g. diabetes, congestive heart failure).

7. Chronic renal disease (BUN and serum creatinine >1.5 times the upper normal limit).

8. History or presence of impaired gastrointestinal motility, or history of extensive small bowel resection (greater than half the length of the small intestine).

9. Use of warfarin or heparin.

10. Use of systemic immunomodulatory medications within 4 weeks of screening.

11. Use of any investigational products within 4 weeks of screening.

12. Fever at time of endoscopy. Subjects can be re-scheduled at a later point after the fever is resolved.

13. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of sever, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease.

HIV positive adolescents already taking tenofovir in their antiretroviral regimen. Must be 10-14 years (n=6) and 18-21 years (n=6). HIV negative adolescents who are otherwise healthy ages10-14 years (n=6) and 18-21 years (n=6). Recruitment will be voluntary from the city/community and outpatient clinics.