The Compartmental Biology of HIV in the Male Genital Tract

Human Immunodeficiency Virus Clinical Trial

Official title:

IGHID 11526 - The Compartmental Biology of HIV in the Male Genital Tract

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02638493
• Other study ID #: 15-2767
• Secondary ID: R01DK108424-01
• Status: Active, not recruiting
• Phase: N/A
• First received: December 10, 2015
• Last updated: October 27, 2016
• Start date: November 2015
• Est. completion date: November 2017

Study information

• Verified date: October 2016
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

Male participants taking tenofovir-emtrictabine (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.

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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: November 2017
• Est. primary completion date: October 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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 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

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes
• Virus Shedding

Locations

Country	Name	City	State
United States	University of North Carolina	Chapel Hill	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. Review. — View Citation

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. Review. — View Citation

Galvin SR, Cohen MS. The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol. 2004 Jan;2(1):33-42. Review. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose	No
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.	Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose	No
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.	Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose	No
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.	Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose	No
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.	Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose	No
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.	Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose	No
Secondary	Tenofovir diphosphate/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	6 time points in a 24 hour dosing interval	No
Secondary	Emtricitabine 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	6 time points in a 24 hour dosing interval	No

External Links

•   University of North Carolina website