The Compartmental Biology of HIV in the Male Genital Tract

NCT02638493 | Completed Results

• 2 other identifiers: 15-2767R01DK108424-01
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Human Immunodeficiency Virus; Virus Shedding

Keywords

HIV; tenofovir-emtricitabine; antiretroviral therapy; Prevention; tenofovir alafenamide

Outcome Measures

Primary Outcomes (6)

• 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.

  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

Secondary Outcomes (2)

• Tenofovir Diphosphate (TFVdp)/Deoxyadenosine Triphosphate (dATP) Ratio in Seminal Mononuclear Cells

  Average concentration in a 24 hour dosing interval

• Emtricitabine Triphosphate (FTCtp)/Deoxyadenosine Triphosphate (dCTP) Ratio in Seminal Mononuclear Cells

  Average concentration in a 24 hour dosing interval

Study Arms (3)

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

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (4)

• 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.

  PMID: 15035007 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.

  PMID: 17438318 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.

  PMID: 20010071 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.

  PMID: 26052661 BACKGROUND

Related Links

• University of North Carolina website

Biospecimen

Retention: SAMPLES WITH DNA

Blood and semen samples

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Julie B. Dumond, PharmD, MS, BCPS, AAHIVP
• Organization: University of North Carolina at Chapel Hill

jdumond@unc.edu

919-966-5017

Study Officials

• Julie Dumond, PharmD, MS

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 10, 2015
• First Posted: December 23, 2015
• Study Start: December 1, 2015
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: July 24, 2017
• Results First Posted: July 24, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)