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

Study Overview
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Brief Summary
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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.

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

Conditions
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HIV

Intervention / Treatment
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* Procedure: Upper endoscopy
* Procedure: Anoscopy
* Drug: Truvada


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort<br>All subjects will undergo all procedures | Procedure: Upper endoscopy<br>* Upper endoscopy with biopsies<br>Procedure: Anoscopy<br>* Anoscopy with biopsies<br>Drug: Truvada<br>* Truvada (tenofovir/emtricitabine) daily as HIV pre-exposure prophylaxis. This medication will not be provided by the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukin-10 (IL-10) and mitochondrially encoded ATP synthase 6 (MT-ATP6) mRNA copy numbers. | Copy numbers per 1000 copies of the housekeeping gene hemoglobin B (HBB) (copies / 1000 HBB copies) | 2-3 months after initiating HIV Pre-exposure prophylaxis | 
| Global transcriptome analysis | 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. | 2-3 months after initiating HIV Pre-exposure prophylaxis |