Relationship of Tenofovir With HIV-1 Suppression in ex Vivo Tissue in Adolescents
Condition: Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Observational

Summary: 
      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.
    


Intervention name(s): flexible sigmoidoscopy or colonoscopy with biopsies
Intervention type(s): Device
Intervention description(s): Lower endoscopy with biopsies (specifically either colonoscopy or flexible sigmoidoscopy) in both HIV-positive subjects already on oral tenofovir , as well as HIV negative subjects. Biopsies will be taken to laboratory for quantification of HIV-1 and drug levels of tenofovir.
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        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.
      
Keywords: HIV; tenofovir; miocrobicide; endoscopy (colonoscopy, sigmoidoscopy); adolescents; pediatrics