Clinical trial NCT02638493: The Compartmental Biology of HIV in the Male Genital Tract
Official title: IGHID 11526 - The Compartmental Biology of HIV in the Male Genital Tract
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Human Immunodeficiency Virus
Virus Shedding
Keywords: HIV
tenofovir-emtricitabine
antiretroviral therapy
Prevention
tenofovir alafenamide
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2015-12-23
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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.

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.

Eligibility 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

Primary outcomes:
measure: Semen Clearance (CL) of Tenofovir
timeFrame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
measure: Semen Clearance (CL) of Emtricitabine
timeFrame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
measure: Semen Clearance (CL) of Tenofovir Diphosphate
timeFrame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
measure: Semen Clearance (CL) of Emtricitabine Triphosphate
timeFrame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
measure: Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Tenofovir Diphosphate
timeFrame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
measure: Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Emtricitabine Triphosphate
timeFrame: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
Secondary outcomes:
measure: Tenofovir Diphosphate (TFVdp)/Deoxyadenosine Triphosphate (dATP) Ratio in Seminal Mononuclear Cells
timeFrame: Average concentration in a 24 hour dosing interval
measure: Emtricitabine Triphosphate (FTCtp)/Deoxyadenosine Triphosphate (dCTP) Ratio in Seminal Mononuclear Cells
timeFrame: Average concentration in a 24 hour dosing interval
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Julie Dumond, PharmD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.7326/0003-4819-146-8-200704170-00010.
citation: 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.
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.