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The Compartmental Biology of HIV in the Male Genital Tract

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02638493
Recruitment Status : Completed
First Posted : December 23, 2015
Results First Posted : July 24, 2017
Last Update Posted : July 24, 2017
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Julie Dumond, PharmD, University of North Carolina, Chapel Hill

Brief Summary:
Male participants taking tenofovir-emtricitabine (TDF/FTC) will provide semen and blood samples which will be analyzed to better understand the pharmacology of antiretroviral therapy in the male genital tract.

Condition or disease
Human Immunodeficiency Virus Virus Shedding

Detailed Description:

8 HIV positive men taking TDF/FTC and 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis will provide multiple semen and blood samples during a 48-hour inpatient visit. 8 HIV positive men taking TAF (tenofovir alafenamide) will provide multiple semen and blood samples during a 48-hour inpatient visit.

Participants will take part in the study for approximately two months. After the screening visit, there is one 2 day overnight visit for intensive PK/PD (pharmacokinetic/pharmacodynamic) sampling. The investigators will study drug concentrations and intracellular endogenous nucleotide concentrations (dATP and dCTP) in seminal plasma and (where appropriate) seminal cells.

Samples will be analyzed through the use of novel laboratory methods to determine the seminal plasma and seminal cell concentrations of tenofovir and emtricitabine. New technologies will be used to better understand compartmental and intracellular antiretroviral pharmacology of nucleoside/tide reverse transcriptase inhibitors. Pharmacokinetic modeling will be used to estimate the primary outcomes.

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Study Type : Observational
Actual Enrollment : 26 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: IGHID 11526 - The Compartmental Biology of HIV in the Male Genital Tract
Actual Study Start Date : December 2015
Actual Primary Completion Date : October 2016
Actual Study Completion Date : October 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Group/Cohort
HIV positive TDF/FTC
8 HIV positive men taking TDF/FTC as treatment
HIV negative
8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis
HIV Positive TAF
8 HIV positive men taking TAF as treatment



Primary Outcome Measures :
  1. Semen Clearance (CL) of Tenofovir [ Time Frame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose ]
    Samples will be analyzed for drug concentrations at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate clearance from semen from a 300mg dose of tenofovir.

  2. Semen Clearance (CL) of Emtricitabine [ Time Frame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose ]
    Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate clearance from semen from a 200mg dose of emtricitabine.

  3. Semen Clearance (CL) of Tenofovir Diphosphate [ Time Frame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose ]
    Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of tenofovir diphosphate, an intracellular metabolite of tenofovir, from seminal mononuclear cells, following a 300mg dose of tenofovir.

  4. Semen Clearance (CL) of Emtricitabine Triphosphate [ Time Frame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose ]
    Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of emtricitabine triphosphate, an intracellular metabolite of emtricitabine, from seminal mononuclear cells, following a 200mg dose of emtricitabine.

  5. Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Tenofovir Diphosphate [ Time Frame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose ]
    Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of tenofovir diphosphate, an intracellular metabolite of tenofovir, from peripheral blood mononuclear cells, following a 300mg dose of tenofovir.

  6. Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Emtricitabine Triphosphate [ Time Frame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose ]
    Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of emtricitabine triphosphate, an intracellular metabolite of emtricitabine, from peripheral blood mononuclear cells, following a 200mg dose of emtricitabine.


Secondary Outcome Measures :
  1. Tenofovir Diphosphate (TFVdp)/Deoxyadenosine Triphosphate (dATP) Ratio in Seminal Mononuclear Cells [ Time Frame: Average concentration in a 24 hour dosing interval ]
    dATP concentrations in seminal mononuclear cells will be measured and compared to tenofovir diphosphate concentrations, using a ratio, and summarized descriptively for each subject, as well as across subjects. As the six seminal cell samples collected per man were pooled for analysis due to low cell recovery, a single ratio value per participant was calculated and summarized by study arm.

  2. Emtricitabine Triphosphate (FTCtp)/Deoxyadenosine Triphosphate (dCTP) Ratio in Seminal Mononuclear Cells [ Time Frame: Average concentration in a 24 hour dosing interval ]
    dCTP concentrations in seminal mononuclear cells will be measured and compared to emtricitabine triphosphate concentrations, using a ratio, and summarized descriptively for each subject, as well as across subjects. As the six seminal cell samples collected per man were pooled for analysis due to low cell recovery, a single ratio value per participant was calculated and summarized by study arm.


Biospecimen Retention:   Samples With DNA
Blood and semen samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
HIV positive and HIV negative men taking TDF/FTC once daily, HIV positive men taking TAF/FTC once daily
Criteria

Inclusion Criteria:

  • Born male between the ages of 18 and 60
  • HIV positive taking TDF/FTC (and a third drug) as treatment; or HIV negative men receiving TDF/FTC as pre-exposure prophylaxis; HIV positive men taking tenofovir alafenamide
  • if on routine treatment must have been taking medication for at least 3 months and adherence to medication as assessed by blood plasma HIV RNA less than 50 copies per mL.
  • documentation of at least 80% adherence to antiretroviral (ART) regimen, through clinician or self-report, with no missed doses in the 3 days prior to the inpatient visit.
  • willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurologic disease that would pose unnecessary risk or interfere with study results.
  • unwilling or unable to abstain from sexual activity 72 hours prior to overnight sampling visit
  • unlikely to remain on current drug regimen during study period
  • anemia that precludes blood donation
  • unable to provide semen specimen
  • current receipt of other medications that may affect endogenous nucleotide concentrations, such as additional HIV nucleoside reverse transcriptase inhibitors, ribavirin, or adefovir

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02638493


Locations
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United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Julie Dumond, PharmD, MS University of North Carolina, Chapel Hill
Additional Information:
Publications:
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Responsible Party: Julie Dumond, PharmD, Assistant Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02638493    
Other Study ID Numbers: 15-2767
R01DK108424-01 ( U.S. NIH Grant/Contract )
First Posted: December 23, 2015    Key Record Dates
Results First Posted: July 24, 2017
Last Update Posted: July 24, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Julie Dumond, PharmD, University of North Carolina, Chapel Hill:
HIV
tenofovir-emtricitabine
antiretroviral therapy
Prevention
tenofovir alafenamide
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases