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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK108424-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| Measure | Description | Time Frame |
|---|---|---|
| Semen Clearance (CL) of Tenofovir | 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. | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
| Semen Clearance (CL) of Emtricitabine | 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. | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
| Semen Clearance (CL) of Tenofovir Diphosphate | 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. | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
| Semen Clearance (CL) of Emtricitabine Triphosphate | 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. | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
| Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Tenofovir Diphosphate | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Tenofovir Diphosphate (TFVdp)/Deoxyadenosine Triphosphate (dATP) Ratio in Seminal Mononuclear Cells | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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HIV positive and HIV negative men taking TDF/FTC once daily, HIV positive men taking TAF/FTC once daily
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| Name | Affiliation | Role |
|---|---|---|
| Julie Dumond, PharmD, MS | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina | Chapel Hill | North Carolina | 27599 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15035007 | Background | Galvin SR, Cohen MS. The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol. 2004 Jan;2(1):33-42. doi: 10.1038/nrmicro794. | |
| 17438318 | Background | Cohen MS, Gay C, Kashuba AD, Blower S, Paxton L. Narrative review: antiretroviral therapy to prevent the sexual transmission of HIV-1. Ann Intern Med. 2007 Apr 17;146(8):591-601. doi: 10.7326/0003-4819-146-8-200704170-00010. |
| Label | URL |
|---|---|
| University of North Carolina website | View source |
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Participants interested in the study were pre-screened for eligibility using an IRB-approved questionnaire.
All participants were recruited at the University of North Carolina at Chapel Hill and surrounding areas, through Institutional Review Board (IRB)-approved advertisements.
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| ID | Title | Description |
|---|---|---|
| FG000 | HIV Positive TDF/FTC | 8 HIV positive men taking TDF/FTC (Tenofovir Disoproxil Fumarate/Emtricitabine) as treatment |
| FG001 | HIV Negative | 8 HIV negative men taking TDF/FTC (Tenofovir Disoproxil Fumarate/Emtricitabine) as pre-exposure prophylaxis |
| FG002 | HIV Positive TAF | 8 HIV positive men taking TAF (Tenofovir Alafenamide) as treatment |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | HIV Positive TDF/FTC | 8 HIV positive men taking TDF/FTC as treatment |
| BG001 | HIV Negative | 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Semen Clearance (CL) of Tenofovir | 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. | Posted | Median | Inter-Quartile Range | L/hr | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
|
Adverse events were collected from the time of informed consent, until end of study enrollment.
does not differ
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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 | HIV Positive TDF/FTC | 8 HIV positive men taking TDF/FTC as treatment | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Viral Pharyngitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Sore throat and temperature reported, rapid strep sent, result negative. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Julie B. Dumond, PharmD, MS, BCPS, AAHIVP | University of North Carolina at Chapel Hill | 919-966-5017 | jdumond@unc.edu |
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| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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Blood and semen samples
| Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
| Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Emtricitabine Triphosphate | 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. | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
| Average concentration in a 24 hour dosing interval |
| Emtricitabine Triphosphate (FTCtp)/Deoxyadenosine Triphosphate (dCTP) Ratio in Seminal Mononuclear Cells | 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. | Average concentration in a 24 hour dosing interval |
| 20010071 | Background | Anderson DJ, Politch JA, Nadolski AM, Blaskewicz CD, Pudney J, Mayer KH. Targeting Trojan Horse leukocytes for HIV prevention. AIDS. 2010 Jan 16;24(2):163-87. doi: 10.1097/QAD.0b013e32833424c8. No abstract available. |
| 26052661 | Background | Joseph SB, Swanstrom R, Kashuba AD, Cohen MS. Bottlenecks in HIV-1 transmission: insights from the study of founder viruses. Nat Rev Microbiol. 2015 Jul;13(7):414-25. doi: 10.1038/nrmicro3471. Epub 2015 Jun 8. |
| BG002 | HIV Positive TAF | 8 HIV positive men taking TAF as treatment |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
8 HIV positive men taking TAF as treatment |
|
|
| Primary | Semen Clearance (CL) of Emtricitabine | 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. | Posted | Median | Inter-Quartile Range | L/hr | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
|
|
|
| Primary | Semen Clearance (CL) of Tenofovir Diphosphate | 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. | Posted | Median | Inter-Quartile Range | fmol/10x6 cells | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
|
|
|
| Primary | Semen Clearance (CL) of Emtricitabine Triphosphate | 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. | Semen (SMC) Steady State Concentrations (Css,ave) of Emtricitabine Triphosphate | Posted | Median | Inter-Quartile Range | fmol/10 E6 cells | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
|
|
|
| Primary | Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Tenofovir Diphosphate | 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. | Posted | Median | Inter-Quartile Range | fmol/10 E6 cells | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
|
|
|
| Primary | Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Emtricitabine Triphosphate | 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. | Posted | Median | Inter-Quartile Range | fmol/10 E6 cells | Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose |
|
|
|
| Secondary | Tenofovir Diphosphate (TFVdp)/Deoxyadenosine Triphosphate (dATP) Ratio in Seminal Mononuclear Cells | 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. | Posted | Median | Inter-Quartile Range | TFVdp:dATP ratio | Average concentration in a 24 hour dosing interval |
|
|
|
| Secondary | Emtricitabine Triphosphate (FTCtp)/Deoxyadenosine Triphosphate (dCTP) Ratio in Seminal Mononuclear Cells | 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. | Posted | Median | Inter-Quartile Range | FTCtp:dCTP ratio | Average concentration in a 24 hour dosing interval |
|
|
|
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | HIV Negative | 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis | 0 | 8 | 0 | 8 | 1 | 8 |
| EG002 | HIV Positive TAF | 8 HIV positive men taking TAF as treatment | 0 | 8 | 0 | 8 | 1 | 8 |
|
| Penile skin irritation | Skin and subcutaneous tissue disorders | Systematic Assessment | Mild skin irritation/soreness following sample |
|
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| D015229 |
| Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |