Effects of the Anti-HIV Pill Truvada on Gene Transcription in the Gastrointestinal Tract of HIV-uninfected Individuals

Overview

As explained in detail in a recently published hypothesis article (Hladik F. A new hypothesis on HIV cure. F1000Research, 4:77 (2015)), the investigators hypothesize that NRTI drugs may reduce the likelihood of HIV eradication by promoting the survival of cells with integrated provirus. In this study, the investigators will test whether daily oral use of two NTRI drugs, tenofovir and emtricitabine (Truvada Pill), induces changes in the upper and lower gut mucosa that are congruent with supporting this hypothesis.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2017

Interventions

  • Procedure: Upper endoscopy
    • Upper endoscopy with biopsies
  • Procedure: Anoscopy
    • Anoscopy with biopsies
  • Drug: Truvada
    • Truvada (tenofovir/emtricitabine) daily as HIV pre-exposure prophylaxis. This medication will not be provided by the study.

Arms, Groups and Cohorts

  • Other: Cohort
    • All subjects will undergo all procedures

Clinical Trial Outcome Measures

Primary Measures

  • Interleukin-10 (IL-10) and mitochondrially encoded ATP synthase 6 (MT-ATP6) mRNA copy numbers.
    • Time Frame: 2-3 months after initiating HIV Pre-exposure prophylaxis
    • Copy numbers per 1000 copies of the housekeeping gene hemoglobin B (HBB) (copies / 1000 HBB copies)
  • Global transcriptome analysis
    • Time Frame: 2-3 months after initiating HIV Pre-exposure prophylaxis
    • Global transcriptome analysis tests for expression changes of any possible gene across the entire human genome in response to Truvada PrEP. The main outcome of such an analysis is the number of genes significantly changing in expression between before and after treatment. We will report that Truvada PrEP up-regulates X number of genes and down-regulates Y number of genes.

Participating in This Clinical Trial

Inclusion Criteria

  • • HIV-negative – Male gender at birth – Age ≥18 years old – Intent to initiate PrEP in the next 1-2 months. – Willingness and ability to provide informed consent for study participation – Willingness to undergo all required study procedures Exclusion Criteria:

  • Creatinine clearance < 60mL/min – Platelet count below the normal reference – Coagulation (PT/PTT) tests above the normal reference – Any prior use of PrEP – Use of PEP within 30 days prior to study entry – Receipt of – anti-coagulant medications (e.g. warfarin). Aspirin is allowable. – Systemic corticosteroid medications – Non-steroidal anti-inflammatory drug (NSAID) use >2 days/week – Signs or symptoms of acute HIV infection within 14 days of study entry – No availability of another person who will drive participant home on days of entry and follow-up procedures. – Plan to leave the Seattle area in the subsequent 2.5 months – Any condition or substance use that, in the opinion of the study investigator, would interfere with study participation.

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Washington
  • Provider of Information About this Clinical Study
    • Principal Investigator: Joanne Stekler, MD MPH, Associate Professor, Division of Allergy & Infectious Diseases – University of Washington
  • Overall Official(s)
    • Joanne Stekler, MD, Principal Investigator, University of Washington

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.