Tenofovir Rectal Douche to Prevent HIV Transmission Among Adolescents (ATN DREAM)
Condition: HIV/AIDS; HIV Prevention
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: Tenofovir Douche
Intervention description: 660 mg TFV in 125 mL hypo-osmolar solution
Intervention MeSH terms: Tenofovir
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: Male
Minimum age: 15 Years
Maximum age: 24 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Tenofovir; Tenofovir Douche

Summary:

      ATN DREAM is an early phase-1, open label study to examine the safety, pharmacokinetics (PK),
      pharmacodynamics (PD), and acceptability of a one-dose tenofovir (TFV) medicated douche. The
      overall goal is to inform the design of an extended safety study of an on-demand and
      behaviorally congruent TFV douche to confer protection from HIV acquisition in an outpatient
      pre-RAI context
    

Eligibility criteria:

        Inclusion Criteria:

          -  Between the ages of 15-24 at Screening

          -  Cisgender male who has sex with other men

          -  Willing and able to communicate in English

          -  Willing and able to provide informed consent to take part in the study

          -  Participant demonstrates capacity to comprehend, evaluate, reason, and express a
             choice about their participation in study

          -  For youth ages 15-17, have parent or caregiver consent to take part in the study

          -  Willing and able to provide adequate locator information

          -  Express initial interest in participating in a douching study

          -  Understand and agree to local HIV/STI reporting requirements

          -  HIV-1 uninfected at screening as documented by Combo Ag/Ab HIV- 1/HIV-2 immunoassay

          -  Willingness and availability to attend all study visits, barring unforeseen
             circumstances

          -  Per participant report at screening, consensual RAI in prior 6 months

          -  Live in or around the Baltimore area.

          -  Willing to abstain from insertion of anything (drug/medication, digits, penis, object,
             sex toy, or douche) into the anorectum for 72 hours before and after each study visit
             and 7 days after the biopsy collection.

          -  Willing to refrain from aspirin, vitamins and herbal supplements, and NSAID use for
             one week before and after each study biopsy visit

          -  Agrees not to participate in other research studies involving drugs and/ or medical
             devices for the study's duration

        Exclusion Criteria:

          -  Participation in research studies involving drugs, medical devices, genital products,
             or vaccines within 30 days of the Enrollment Visit.

          -  History of Hepatitis B infection, as documented by positive HBsAg at screening

          -  ≥ Grade 2 laboratory abnormality at baseline as defined by Division of AIDS Table for
             Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 -
             July 2017, and Addendum 3 (Rectal Grading Tables for Use in Microbicide Studies)

          -  Self-report as having used TDF 300 mg/FTC 200 mg (Truvada®) or TAF 25 mg/FTC 200 mg
             (Descovy®) as HIV PrEP or Truvada as PEP within three weeks of dosing visit.

          -  Significant colorectal symptom(s) as determined by medical history or by participant
             self-report (including but not limited to presence of any unresolved injury,
             infectious or inflammatory condition of the local mucosa, history of inflammatory
             bowel disease, presence of symptomatic hemorrhoids, and presence of any painful
             anorectal conditions that would be tender to manipulation)

          -  At screening or within the past 2 months: participant- reported symptoms and/or
             clinical or laboratory diagnosis of active rectal infection requiring treatment per
             current CDC guidelines. Infections requiring treatment include Chlamydia (CT),
             gonorrhea (GC), syphilis, active HSV lesions, chancroid, genital sores or ulcers, and,
             if clinically indicated, genital warts. Note that HSV seropositivity with no active
             genital lesions is not an exclusion criterion. (Note: if an STI apart from HIV is
             detected, the participant will be referred for treatment and can be retested in 30
             days and rescreened once).

          -  History of an underlying clinically significant cardiac arrhythmia or renal disease
             (including creatinine clearance <60 mL/min using Cockcroft-Gault equation)

          -  Serum phosphate < 2.3 mg/dL

          -  History of significant gastrointestinal bleeding

          -  Current use of warfarin or heparin or other anticoagulant medications associated with
             increased risk for bleeding following mucosal biopsy (e.g., daily high dose aspirin
             [>81 mg], NSAIDs, or Pradaxa®)

          -  Use of systemic or anorectal immunomodulatory medications within 4 weeks of enrollment
             or planned use at any time during study participation

          -  Per participant report, use of any rectally administered products containing N-9
             (including condoms) or investigational products within 4 weeks of enrollment, or
             planned use of either at any time during study participation

          -  Known allergic reaction to TFV or other components of the test articles

          -  Current known HIV-positive partner(s)

          -  History of recurrent urticaria

          -  Symptoms suggestive of acute HIV seroconversion at screening and enrollment

          -  Any other condition or prior therapy that, in the opinion of the investigator, would
             preclude informed consent, make study participation unsafe, make the individual
             unsuitable for the study or unable to comply with the study requirements.

          -  Presence of substance use (e.g., Cocaine, Marijuana, Opiates, Amphetamines,
             Methamphetamine, Phencyclidine, Benzodiazepine, Methadone, Barbiturate, Tricyclic
             Antidepressants, Oxycodone, and Propoxyphene) in one-step urine drug test.