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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort | All subjects will undergo all procedures |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Upper endoscopy | Procedure | Upper endoscopy with biopsies |
| |
| Anoscopy |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
• HIV-negative
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
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.
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The study population is a prospective observational study of cis-gender male persons initiating HIV pre-exposure prophylaxis.
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| Name | Affiliation | Role |
|---|---|---|
| Joanne Stekler, MD | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Harborview Medical Center | Seattle | Washington | 98104 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort | All subjects will undergo all procedures Upper endoscopy: Upper endoscopy with biopsies Anoscopy: Anoscopy with biopsies Truvada: Truvada (tenofovir/emtricitabine) daily as HIV pre-exposure prophylaxis. This medication will not be provided by the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort | All subjects will undergo all procedures Upper endoscopy: Upper endoscopy with biopsies Anoscopy: Anoscopy with biopsies Truvada: Truvada (tenofovir/emtricitabine) daily as HIV pre-exposure prophylaxis. This medication will not be provided by the study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Duodenal biopsies | Posted | Number | genes | 2-3 months after initiating HIV Pre-exposure prophylaxis | Genes | Genes |
|
Duration of study enrollment, approximately 2 months
Serious adverse events would have been collected as part of the protocol, however, given that this was not an intervention study, only adverse events that might have been attributed to study procedures (i.e. specimen collection) would have been reported, had any occurred.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort | All subjects will undergo all procedures Upper endoscopy: Upper endoscopy with biopsies Anoscopy: Anoscopy with biopsies Truvada: Truvada (tenofovir/emtricitabine) daily as HIV pre-exposure prophylaxis. This medication will not be provided by the study. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Joanne Stekler | University of Washington | 206-744-8312 | jstekler@uw.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 9, 2015 | Mar 30, 2023 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D005773 | Gastroscopy |
| D011351 | Proctoscopy |
| D000069480 | Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination |
| ID | Term |
|---|---|
| D016099 | Endoscopy, Gastrointestinal |
| D016145 | Endoscopy, Digestive System |
| D003938 | Diagnostic Techniques, Digestive System |
| D019937 | Diagnostic Techniques and Procedures |
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| Procedure |
Anoscopy with biopsies |
|
| Truvada | Drug | Truvada (tenofovir/emtricitabine) daily as HIV pre-exposure prophylaxis. This medication will not be provided by the study. |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
| Genes |
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| 0 |
| 9 |
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| D003933 | Diagnosis |
| D004724 | Endoscopy |
| D003949 | Diagnostic Techniques, Surgical |
| D013505 | Digestive System Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D019060 | Minimally Invasive Surgical Procedures |
| D000068698 | Tenofovir |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D000068679 | Emtricitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |