The Compartmental Biology of HIV in the Male Genital Tract

University of North Carolina (UNC)

Status

Completed

Conditions

Human Immunodeficiency Virus

Virus Shedding

Study type

Observational

Funder types

Other

NIH

Identifiers

NCT02638493

R01DK108424-01 (U.S. NIH Grant/Contract)

15-2767

Details and patient eligibility

About

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.

Full 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.

Enrollment

26 patients

Sex

Male

Ages

18 to 60 years old

Volunteers

Accepts Healthy Volunteers

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