Sex Hormone Therapy and Mucosal Tissues

NCT02983110 | Completed

• 1 other identifier: 16-2122
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to better understand how sex hormone therapy that is used to treat women for menopausal symptoms, men with low testosterone, or as hormone therapy for transgender women, affects a class of medications called NRTIs (nucleoside reverse transcriptase inhibitors) used to treat and prevent HIV infection. The two most commonly used NRTIs are tenofovir and emtricitabine, which are the components of the drug Truvada and also included in the combination products Atripla, Complera, and Stribild. The medication's ability to work effectively may be altered when someone is also taking sex hormone therapy. In order to determine this effect, samples will be collected from some parts of the body where HIV makes copies. These samples will be measured for the levels of HIV medication, HIV virus and sex hormones that are present. The samples that will be looked at in this study include blood, cells from the vagina, semen, and tissue biopsies from the female genital tract and rectum.

Conditions

Hiv

Keywords

Hormones, Transgender

Outcome Measures

Primary Outcomes (2)

• Quantification of tenofovir/emtricitabine active metabolite (TFVdp/FTCtp) concentrations in ectocervical/vaginal (cisgender women) and rectal (all cohorts) tissue biopsies by LC-MS/MS.

  (TFVdp/FTCtp)

  Samples collected within 24 hours post-dose

• Quantification of tenofovir/emtricitabine active metabolite (TFVdp/FTCtp) concentrations in PBMCs (all cohorts) and seminal mononuclear cells (cisgender men).

  PBMC concentrations

  Samples collected within 24 hours post-dose

Secondary Outcomes (2)

• Quantification of HIV RNA concentrations

  Samples collected within 24 hours post-dose

• Quantification of estradiol/progesterone (cisgender and transgender women) and testosterone (cisgender men) concentrations in blood serum.

  Samples collected within 24 hours post-dose

Study Arms (3)

Cohort B

Group B will be HIV Infected post-menopausal women who are not receiving hormonal therapy to provide tissue, blood, and cells

Procedure: Anoscopy with Rectal Tissue Sampling; Procedure: Phlebotomy; Procedure: Female Genital Tract Sampling

Cohort C

Group C will be HIV infected transgendered women receiving hormone therapy to provide tissue and blood

Procedure: Anoscopy with Rectal Tissue Sampling; Procedure: Phlebotomy

Cohort E

Group E will be HIV infected men

Procedure: Anoscopy with Rectal Tissue Sampling; Procedure: Phlebotomy

Interventions

Anoscopy with Rectal Tissue Sampling PROCEDURE

All subjects will provide 10 pieces of rectal tissue

Cohort B; Cohort C; Cohort E

Phlebotomy PROCEDURE

• Procedure: Blood plasma/serum collection Approximately 17 mL of blood will be taken from each subject just prior to tissue sampling.

Cohort B; Cohort C; Cohort E

Female Genital Tract Sampling PROCEDURE

Cohorts B only will have cervical cells, cervical tissue, and vaginal tissue collected

Cohort B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will consist of 20 HIV positive men and women between 18-65 years of age (inclusive) with an intact gastrointestinal tract, uterus/cervix (if cisgender women), and male genital tract (if cisgender man) who are available to complete all study procedures at UNC.

You may qualify if:

• HIV-positive adults aged 18-65, inclusive on the date of screening, clinically healthy, with an intact gastrointestinal tract. Any screening test may be repeated once in the screening window to confirm or verify eligibility.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all the pertinent details of the study.
• Willing and able to comply with scheduled visits, treatment plan laboratory tests, and other trial procedures
• Subjects must not be actively involved in the conception process, currently pregnant/lactating/ or in the immediate post-partum period.
• Subjects must be willing to abstain from all sexual activity, and all intravaginal and intrarectal products for at least 72 hours prior to the sampling day, until seven days later
• HIV RNA viral load undetectable (\<50 copies/mL or less per institution) within at least the previous six months prior to screening. Repeat HIV RNA Viral load testing may be conducted at screening, if indicated.
• \>80% adherent to their antiretroviral regimen per self-report, and a compliant diary card 5 days before intensive sampling
• Actively adherent to an antiretroviral regimen containing both tenofovir (TDF) and emtracitabine (FTC) for \>1 month (if switched from previous regimen) or \>3 months (if previously antiretroviral naive) as part of their standard clinic care
• Negative, or treated, sexually transmitted infections at screening including syphilis, gonorrhea, chlamydia, and trichomoniasis
• All subjects must have an estimated calculated creatinine clearance of (eCcr) at least 60mL/min by the Cockcroft-Gault formula
• No clinical or surgical abnormalities (i.e. hysterectomy) that would preclude sample collection
• Hemoglobin Grade 2 or lower, with no clinical significant medical issues that would preclude blood sampling
• Coagulation testing Grade 2 or lower, with no clinically significant medical issues that would preclude tissue sampling

You may not qualify if:

• Age outside of desired range
• Subject is HIV negative
• Impaired renal function, as documented with a creatinine clearance \<60mL/min with the Cockcroft-Gault equation
• Receiving an antiretorivral regimen that does not include TDF/FTC, or adherent to a TDF/FTC regimen less than one month, or patient is unlikely to remain on this regimen during the sampling period
• Less than 80% adherence to anti-retroviral medications, and more than 3 missed doses in the month preceding enrollment
• Subject is not able or willing to follow the diet and lifestyle guidelines necessary for the study period
• Active, untreated, sexually transmitted infection, including syphilis, gonorrhea, chlamydia or trichomoniasis or symptomatic bacterial vaginosis
• Clinical, laboratory, or surgical abnormalities that would preclude sample collection (for example but not limited to: hysterectomy)
• Subjects actively involved in the conception process, currently pregnant or lactating, or immediately post-partum

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

Clinical and Translational Research Center, UNC Hospitals

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (4)

• Cottrell ML, Yang KH, Prince HM, Sykes C, White N, Malone S, Dellon ES, Madanick RD, Shaheen NJ, Hudgens MG, Wulff J, Patterson KB, Nelson JA, Kashuba AD. A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine. J Infect Dis. 2016 Jul 1;214(1):55-64. doi: 10.1093/infdis/jiw077. Epub 2016 Feb 24.

  PMID: 26917574 BACKGROUND

• Nicol MR, Fedoriw Y, Mathews M, Prince HM, Patterson KB, Geller E, Mollan K, Mathews S, Kroetz DL, Kashuba AD. Expression of six drug transporters in vaginal, cervical, and colorectal tissues: Implications for drug disposition in HIV prevention. J Clin Pharmacol. 2014 May;54(5):574-83. doi: 10.1002/jcph.248. Epub 2014 Jan 2.

  PMID: 24343710 BACKGROUND

• Cottrell ML, Prince HM, Allmon A, Mollan KR, Hudgens MG, Sykes C, White N, Malone S, Dellon ES, Madanick RD, Shaheen NJ, Patterson KB, Kashuba AD. Cervicovaginal and Rectal Fluid as a Surrogate Marker of Antiretroviral Tissue Concentration: Implications for Clinical Trial Design. J Acquir Immune Defic Syndr. 2016 Aug 15;72(5):498-506. doi: 10.1097/QAI.0000000000000996.

  PMID: 26999532 BACKGROUND

• Cottrell ML, Prince HMA, Schauer AP, Sykes C, Maffuid K, Poliseno A, Chun TW, Huiting E, Stanczyk FZ, Peery AF, Dellon ES, Adams JL, Gay C, Kashuba ADM. Decreased Tenofovir Diphosphate Concentrations in a Transgender Female Cohort: Implications for Human Immunodeficiency Virus Preexposure Prophylaxis. Clin Infect Dis. 2019 Nov 27;69(12):2201-2204. doi: 10.1093/cid/ciz290.

  PMID: 30963179 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Proctoscopy; Phlebotomy

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

Intervention Hierarchy (Ancestors)

Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Punctures; Therapeutics; Investigative Techniques

Study Officials

• Mackenzie Cottrell, PharmD

  UNC Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 6, 2016
• Study Start: November 1, 2016
• Primary Completion: October 1, 2018
• Study Completion: October 15, 2018
• Last Updated: December 6, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)