HIV
Conditions
Brief summary
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.
Interventions
PROCEDUREUpper endoscopy
Upper endoscopy with biopsies
PROCEDUREAnoscopy
Anoscopy with biopsies
DRUGTruvada
Truvada (tenofovir/emtricitabine) daily as HIV pre-exposure prophylaxis. This medication will not be provided by the study.
Sponsors
University of Washington
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global Transcriptome Analysis | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Cohort |
|---|---|
| Age, Continuous | 30 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
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.
Time frame: 2-3 months after initiating HIV Pre-exposure prophylaxis
Population: Duodenal biopsies
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort | Global Transcriptome Analysis | Up-regulated | 116 genes |
| Cohort | Global Transcriptome Analysis | Down-regulated | 135 genes |