Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03976752
• Collaborator: Centers for Disease Control and Prevention (U.S. Fed)
• Enrollment: 41
• Location: 1
• Arms: 5
• Actual Duration (Months): 6.3
• Patients Per Site Per Month: 6.5

Study Details

Study Description

Brief Summary

This study is being conducted to determine if the uptake of anti-HIV medication, called Genvoya®, at different time-frames, is different at several body sites, including mucosal tissues. This medication might be considered for on-demand PEP regimens in the future.

Condition or Disease	Intervention/Treatment	Phase
HIV/AIDS	Drug: Genvoya	Phase 1

Detailed Description

Men who have sex with men (MSM) continue to be disproportionately affected by HIV. The majority of MSM acquire HIV after exposure to the rectal mucosa through unprotected receptive anal intercourse. Post-exposure-prophylaxis (PEP) is an intervention that is used to prevent HIV infection soon (72 hours) after a potential exposure. HIV-negative people with a possible exposure to HIV are instructed to take 28 days of a combination anti-HIV medication regimen, Truvada® + Raltegravir.

This study is being conducted to determine if the uptake of another anti-HIV medication, called Genvoya®, at different time-frames, is different at several body sites, including mucosal tissues. This medication might be considered for on-demand PEP regimens in the future.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens
• Actual Study Start Date: Mar 13, 2019
• Actual Primary Completion Date: Sep 20, 2019
• Actual Study Completion Date: Sep 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Pre-drug Participants enrolled in the pre-drug arm will not receive any drug. At visit 2, they will undergo blood, urine, penile swab, cheek swab, rectal swab and rectal biopsy collection.
Experimental: Genvoya - 2 and 48 hours specimen collection Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Drug: Genvoya; Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.; Other Names: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide
Experimental: Genvoya - 4 and 72 hours specimen collection Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Drug: Genvoya; Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.; Other Names: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide
Experimental: Genvoya - 24 and 96 hours specimen collection Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Drug: Genvoya; Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.; Other Names: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide
Experimental: Genvoya - Single time point specimen collection Specimen collection 8 hours after taking the medication in the clinic (visit 4).	Drug: Genvoya; Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.; Other Names: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide

Outcome Measures

Primary Outcome Measures

1. Plasma Concentration of Tenofovir (TFV) [Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication]

   Median drug concentrations of the TFV component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

2. Plasma Concentration of Emtricitabine (FTC) [Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication]

   Median drug concentrations of the FTC component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

3. Plasma Concentration of Elvitegravir (EVG) [Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication]

   Median drug concentrations of the EVG component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

Secondary Outcome Measures

1. Peripheral Blood Mononuclear Cell (PBMC) Concentration of Tenofovir-diphosphate (TFV-DP) [Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication]

   A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round nucleus: lymphocytes (T cells, B cells, natural killer (NK) cells) and monocytes. Median drug concentrations were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

2. Peripheral Blood Mononuclear Cell (PBMC) Concentration of Emtricitabine-triphosphate (FTC-TP) [Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication]

   A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round nucleus: lymphocytes (T cells, B cells, NK cells) and monocytes. Median drug levels were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

Other Outcome Measures

1. Rectal Tissue Concentration of Tenofovir (TFN) [Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication]

   Median drug concentrations in rectal tissue of the TFN component of Genvoya were determined at baseline and at each of the protocol specified time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

2. Rectal Tissue Concentration of Emtricitabine (FTC) [Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication]

   Median drug concentrations in rectal tissue of the FTC component of Genvoya were determined at baseline and at each of the protocol specified time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

3. Rectal Tissue Concentration of Elvitegravir (EVG) [Baseline, and 2, 4, 8, 24, 72, 96 hours after taking the second dose of medication]

   Median drug concentrations in rectal tissue of the EVG component of Genvoya were determined at baseline and at each of the protocol specified time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

4. Rectal Tissue Concentration of Tenofovir-diphosphate (TFV-DP) [Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication]

   Median drug concentrations of TFV-DP in rectal tissue were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

5. Rectal Tissue Concentration of Emtricitabine-triphosphate (FTC-TP) [Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication]

   Median drug concentrations of FTC-TP in rectal tissue were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. HIV-negative man who reports receptive anal sex with another man in the last 6 months

2. Aged 18-49 years

3. Not currently taking PrEP and no plans to initiate during study

4. Not currently taking PEP

5. Able to provide informed consent in English

6. No plans for relocation in the next 3 months

7. Willing to undergo peripheral blood, penile swabs, urine, and rectal biopsy sampling

8. Willing to use study products as directed

9. Willing to abstain from receptive anal intercourse 3 days prior to starting study product and for the duration of the study and for 7 days after any rectal biopsy procedure.

10. Hepatitis B surface antigen (HBsAg) must be negative (screening lab test)

11. Creatine clearance >60 ml/min

Exclusion Criteria:

1. History of inflammatory bowel disease or other inflammatory, infiltrative, infectious or vascular condition involving the lower gastrointestinal tract that, in the judgment of the investigators, may be worsened by study procedures or may significantly distort the anatomy of the distal large bowel

2. Currently infected with hepatitis virus and/ or have liver disease

3. Current or chronic history of kidney disease

4. Significant laboratory abnormalities at baseline visit, including but not limited to:

5. Hgb ≤ 10 g/dL

6. Partial thromboplastin time (PTT) > 1.5x upper limit of normal (ULN) or international normalized ratio (INR) > 1.5x ULN

7. Platelet count <100,000

8. Creatinine clearance <60

9. HBsAg reactive

10. Any known medical condition that, in the judgment of the investigators, increases the risk of local or systemic complications of endoscopic procedures or pelvic examination, including but not limited to:

11. Uncontrolled or severe cardiac arrhythmia

12. Recent major abdominal, cardiothoracic, or neurological surgery

13. History of uncontrolled bleeding diathesis

14. History of colonic, rectal, or vaginal perforation, fistula, or malignancy

15. History or evidence on clinical examination of ulcerative, suppurative, or proliferative lesions of the anorectal mucosa, or untreated sexually transmitted disease with mucosal involvement

16. Continued need for, or use during the 14 days prior to enrollment, of the following medications:

17. Aspirin or more than 4 doses of NSAIDs

18. Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents

19. Any form of rectally administered agent besides lubricants or douching used for sexual intercourse

20. Continued need for, or use during the 90 days prior to enrollment, of the following medications:

21. Systemic immunomodulatory agents

22. Supraphysiologic doses of steroids (short course steroids less than 7 days duration, allowable at the discretion of the investigators)

23. Experimental medications, vaccines, or biologicals

24. Intent to use HIV antiretroviral pre/post-exposure prophylaxis (PrEP or PEP) during the study, outside of the study procedures

25. Symptoms of an untreated rectal sexually transmitted infection (e.g. rectal pain, discharge, bleeding, etc.)

26. Current use of hormonal therapy

27. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements.

28. Participants taking potent inhibitors (e.g. itraconazole, diltiazem) or inducers (e.g. rifampin, phenytoin) of the CYP3A4 enzyme that also metabolizes Genvoya will be excluded from the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hope Clinic	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University
• Centers for Disease Control and Prevention

Investigators

• Principal Investigator: Colleen Kelley, MD, Emory University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 1, 2019

More Information

Publications

None provided.

• Responsible Party: Colleen Kelley, Associate Professor, Emory University
• ClinicalTrials.gov Identifier: NCT03976752
• Other Study ID Numbers: IRB00108386
• First Posted: Jun 6, 2019
• Last Update Posted: Aug 13, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Colleen Kelley, Associate Professor, Emory University: HIV; MSM; Anti-retrovirals; Pharmacokinetics; Peri-exposure HIV prophylaxis
• Additional relevant MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Tenofovir; Emtricitabine; Cobicistat; Emtricitabine tenofovir alafenamide; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Elvitegravir

Study Results

Participant Flow

Recruitment Details

Participants were recruited from the Hope Clinic in Atlanta, Georgia, USA. Participant enrollment began on March 13, 2019 and all follow up was completed September 20, 2019.

Pre-assignment Detail

After the completion of enrollment in the Pre-drug arm, enrollment began sequentially in Arm A, followed by Arm B and Arm C. Arms A, B, and C were further broken down into two different sub-groups, determining the timing of the rectal swab and biopsy procedure. Arm D was enrolled last and included a single time point specimen collection. Participants were able to take part in more than one study arm, with at least a 6 week period after completion of one study arm before beginning another one.

Arm/Group Title	Pre-drug	Genvoya
Arm/Group Description	Participants enrolled in the pre-drug arm will not receive any drug. At visit 2, they will undergo blood, urine, penile swab, cheek swab, rectal swab and rectal biopsy collection.	Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic. Participants took Genvoya and had specimens collected at different time points. Arm A: specimen collection occurred 2 hours and after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5) Arm B: specimen collection occurred 4 hours and after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5) Arm C: specimen collection occurred 24 hours and after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5) Arm D: specimen collection occurred 8 hours after taking the medication in the clinic (visit 4), for a single time point of specimen collection
Period Title: Overall Study
STARTED	4	37
Started Study Arm A	0	14
Completed Study Arm A	0	8
Started Study Arm B	0	8
Completed Study Arm B	0	8
Started Study Arm C	0	11
Completed Study Arm C	0	8
Started Study Arm D	0	6
Completed Study Arm D	0	4
COMPLETED	3	28
NOT COMPLETED	1	9

Baseline Characteristics

Arm/Group Title	Pre-drug	Genvoya	Total
Arm/Group Description	Participants enrolled in the pre-drug arm did not receive any drug. At visit 2, they underwent blood, urine, penile swab, cheek swab, rectal swab and rectal biopsy collection.	Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic. Participants took Genvoya and had specimens collected at different time points. Arm A: specimen collection occurred 2 hours and after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5) Arm B: specimen collection occurred 4 hours and after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5) Arm C: specimen collection occurred 24 hours and after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5) Arm D: specimen collection occurred 8 hours after taking the medication in the clinic (visit 4), for a single time point of specimen collection	Total of all reporting groups
Overall Participants	4	37	41
Age (Count of Participants)
<=18 years	0 0%	1 2.7%	1 2.4%
Between 18 and 65 years	4 100%	36 97.3%	40 97.6%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	4 100%	37 100%	41 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 100%	26 70.3%	30 73.2%
White	0 0%	7 18.9%	7 17.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	4 10.8%	4 9.8%
Region of Enrollment (Count of Participants)
United States	4 100%	37 100%	41 100%

Outcome Measures

1. Primary Outcome

Title	Plasma Concentration of Tenofovir (TFV)
Description	Median drug concentrations of the TFV component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.
Time Frame	Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Outcome Measure Data

Analysis Population Description

Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

Arm/Group Title	Genvoya - 2 and 48 Hours Specimen Collection	Genvoya - 4 and 72 Hours Specimen Collection	Genvoya - 24 and 96 Hours Specimen Collection	Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Measure Participants	8	8	8	4
Baseline	0	0	0	0
2 hours	0
4 hours	0
8 hours	0
24 hours	0
48 hours	0
72 hours	0
96 hours	0

2. Primary Outcome

Title	Plasma Concentration of Emtricitabine (FTC)
Description	Median drug concentrations of the FTC component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.
Time Frame	Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Outcome Measure Data

Analysis Population Description

Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

Arm/Group Title	Genvoya - 2 and 48 Hours Specimen Collection	Genvoya - 4 and 72 Hours Specimen Collection	Genvoya - 24 and 96 Hours Specimen Collection	Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Measure Participants	8	8	8	4
Baseline	0	0	0	0
2 hours	2710
4 hours	1725
8 hours	300
24 hours	113
48 hours	0
72 hours	0
96 hours	0

3. Primary Outcome

Title	Plasma Concentration of Elvitegravir (EVG)
Description	Median drug concentrations of the EVG component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.
Time Frame	Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Outcome Measure Data

Analysis Population Description

Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

Arm/Group Title	Genvoya - 2 and 48 Hours Specimen Collection	Genvoya - 4 and 72 Hours Specimen Collection	Genvoya - 24 and 96 Hours Specimen Collection	Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Measure Participants	8	8	8	4
Baseline	0	0	0	0
2 hours	2243
4 hours	1818
8 hours	283
24 hours	232
48 hours	0
72 hours	0
96 hours	0

4. Secondary Outcome

Title	Peripheral Blood Mononuclear Cell (PBMC) Concentration of Tenofovir-diphosphate (TFV-DP)
Description	A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round nucleus: lymphocytes (T cells, B cells, natural killer (NK) cells) and monocytes. Median drug concentrations were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.
Time Frame	Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Outcome Measure Data

Analysis Population Description

Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

Arm/Group Title	Genvoya - 2 and 48 Hours Specimen Collection	Genvoya - 4 and 72 Hours Specimen Collection	Genvoya - 24 and 96 Hours Specimen Collection	Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Measure Participants	8	8	8	4
Baseline	0	0	0	0
2 hours	569
4 hours	621
8 hours	375
24 hours	429
48 hours	291
72 hours	158
96 hours	117

5. Secondary Outcome

Title	Peripheral Blood Mononuclear Cell (PBMC) Concentration of Emtricitabine-triphosphate (FTC-TP)
Description	A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round nucleus: lymphocytes (T cells, B cells, NK cells) and monocytes. Median drug levels were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.
Time Frame	Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Outcome Measure Data

Analysis Population Description

Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

Arm/Group Title	Genvoya - 2 and 48 Hours Specimen Collection	Genvoya - 4 and 72 Hours Specimen Collection	Genvoya - 24 and 96 Hours Specimen Collection	Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Measure Participants	8	8	8	4
Baseline	0	0	0	0
2 hours	7705
4 hour	7800
8 hours	6855
24 hours	5140
48 hours	2120
72 hours	955
96 hours	714

6. Other Pre-specified Outcome

Title	Rectal Tissue Concentration of Tenofovir (TFN)
Description	Median drug concentrations in rectal tissue of the TFN component of Genvoya were determined at baseline and at each of the protocol specified time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.
Time Frame	Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Outcome Measure Data

Analysis Population Description

Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

Arm/Group Title	Genvoya - 2 and 48 Hours Specimen Collection	Genvoya - 4 and 72 Hours Specimen Collection	Genvoya - 24 and 96 Hours Specimen Collection	Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Measure Participants	8	8	8	4
Baseline	0	0	0	0
2 hours	0
4 hours	0.30
8 hours	0.01
24 hours	0.03
48 hours	0
72 hours	0
96 hours	0

7. Other Pre-specified Outcome

Title	Rectal Tissue Concentration of Emtricitabine (FTC)
Description	Median drug concentrations in rectal tissue of the FTC component of Genvoya were determined at baseline and at each of the protocol specified time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.
Time Frame	Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Outcome Measure Data

Analysis Population Description

Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

Arm/Group Title	Genvoya - 2 and 48 Hours Specimen Collection	Genvoya - 4 and 72 Hours Specimen Collection	Genvoya - 24 and 96 Hours Specimen Collection	Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Measure Participants	8	8	8	4
Baseline	0	0	0	0
2 hours	9.54
4 hours	9.25
8 hours	0.17
24 hours	1.23
48 hours	0.02
72 hours	0
96 hours	0.02

8. Other Pre-specified Outcome

Title	Rectal Tissue Concentration of Elvitegravir (EVG)
Description	Median drug concentrations in rectal tissue of the EVG component of Genvoya were determined at baseline and at each of the protocol specified time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.
Time Frame	Baseline, and 2, 4, 8, 24, 72, 96 hours after taking the second dose of medication

Outcome Measure Data

Analysis Population Description

Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

Arm/Group Title	Genvoya - 2 and 48 Hours Specimen Collection	Genvoya - 4 and 72 Hours Specimen Collection	Genvoya - 24 and 96 Hours Specimen Collection	Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Measure Participants	8	8	8	4
Baseline	0	0	0	0
2 hours	51.23
4 hours	41.47
8 hours	0.31
24 hours	0.60
48 hours	1.03
72 hours	0
96 hours	0.02

9. Other Pre-specified Outcome

Title	Rectal Tissue Concentration of Tenofovir-diphosphate (TFV-DP)
Description	Median drug concentrations of TFV-DP in rectal tissue were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.
Time Frame	Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Outcome Measure Data

Analysis Population Description

Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

Arm/Group Title	Genvoya - 2 and 48 Hours Specimen Collection	Genvoya - 4 and 72 Hours Specimen Collection	Genvoya - 24 and 96 Hours Specimen Collection	Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Measure Participants	8	8	8	4
Baseline	0	0	0	0
2 hours	39.1
4 hours	45.9
8 hours	23.7
24 hours	20.2
48 hours	18.2
72 hours	11.9
96 hours	14.7

10. Other Pre-specified Outcome

Title	Rectal Tissue Concentration of Emtricitabine-triphosphate (FTC-TP)
Description	Median drug concentrations of FTC-TP in rectal tissue were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.
Time Frame	Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Outcome Measure Data

Analysis Population Description

Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

Arm/Group Title	Genvoya - 2 and 48 Hours Specimen Collection	Genvoya - 4 and 72 Hours Specimen Collection	Genvoya - 24 and 96 Hours Specimen Collection	Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).	Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).	Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).	Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Measure Participants	8	8	8	4
Baseline	0	0	0	0
2 hours	187.5
4 hours	198.2
8 hours	116.5
24 hours	104.3
48 hours	56.3
72 hours	15.1
96 hours	12.5

Adverse Events

Time Frame	Data on adverse events were collected from the time of study enrollment, at the screening visit, through two days after the biopsy (up to seven weeks total).
Adverse Event Reporting Description	Adverse events are reported per intervention (two participants were in multiple study arms).
Arm/Group Title	Pre-drug		Genvoya - 2 and 48 Hours Specimen Collection		Genvoya - 4 and 72 Hours Specimen Collection		Genvoya - 24 and 96 Hours Specimen Collection		Genvoya - Single Time Point Specimen Collection
Arm/Group Description	Participants enrolled in the pre-drug arm will not receive any drug. At visit 2, they will undergo blood, urine, penile swab, cheek swab, rectal swab and rectal biopsy collection.		Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5). Genvoya: Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.		Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5). Genvoya: Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.		Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5). Genvoya: Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.		Specimen collection 8 hours after taking the medication in the clinic (visit 4). Genvoya: Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.
All Cause Mortality
	Pre-drug		Genvoya - 2 and 48 Hours Specimen Collection		Genvoya - 4 and 72 Hours Specimen Collection		Genvoya - 24 and 96 Hours Specimen Collection		Genvoya - Single Time Point Specimen Collection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/14 (0%)		0/8 (0%)		0/11 (0%)		0/6 (0%)
Serious Adverse Events
	Pre-drug		Genvoya - 2 and 48 Hours Specimen Collection		Genvoya - 4 and 72 Hours Specimen Collection		Genvoya - 24 and 96 Hours Specimen Collection		Genvoya - Single Time Point Specimen Collection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/14 (0%)		0/8 (0%)		0/11 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Pre-drug		Genvoya - 2 and 48 Hours Specimen Collection		Genvoya - 4 and 72 Hours Specimen Collection		Genvoya - 24 and 96 Hours Specimen Collection		Genvoya - Single Time Point Specimen Collection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/14 (0%)		0/8 (0%)		0/11 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.