Body Compartment PK for New HIV Pre-exposure Prophylaxis Modalities

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02985996
• Collaborator: Centers for Disease Control and Prevention (U.S. Fed)
• Enrollment: 48
• Location: 1
• Arms: 5
• Actual Duration (Months): 9.7
• Patients Per Site Per Month: 4.9

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the ability of new anti-HIV agents to penetrate different body compartments in HIV negative men who have sex with men and transgender women. These new agents might be considered for pre-exposure prophylaxis regimens in the future. This study will include 90 healthy, HIV-negative men who have sex with men and transgender women who are not taking hormones aged 18-49 years. Participant must be willing to participate in 1 of the 3 study phases, be willing to take Truvada® (PrEP) or Genvoya®, and willing to undergo blood draws, urethral swabs, and rectal biopsy procedures.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Truvada; Drug: Genvoya	Phase 1

Detailed Description

Men who have sex with men (MSM) and Transgender women (TGW) who have sex with men continue to be disproportionately affected by HIV. Over 60% of new HIV infections in the US occur among MSM. The majority of HIV infections among MSM and TGW occur through exposure to the rectal mucosa during receptive anal intercourse (RAI). Pre-exposure prophylaxis (PrEP) is a new HIV prevention method that is recommended by CDC and WHO for MSM at risk of HIV infection. PrEP entails taking an anti-HIV medication (Truvada®; tenofovir/emtricitabine) on a daily basis to prevent HIV infection. However, current tenofovir- based regimens have shown to have side effects that researchers are hoping to reduce in newly developed anti-HIV agents. This study is designed to examine the ability of these new agents to penetrate mucosal tissues and potentially prevent HIV infection during RAI exposure for MSM and TGW.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Body Compartment PK for New HIV Pre-exposure Prophylaxis Modalities
• Actual Study Start Date: Feb 6, 2017
• Actual Primary Completion Date: Nov 29, 2017
• Actual Study Completion Date: Nov 29, 2017

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Phase I/Pre-Drug Ten participants will be asked to complete study phase 1. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Experimental: Phase II/Genvoya Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Drug: Genvoya; Genvoya is a 1-pill, once-a-day prescription medicine used to treat HIV-1. Genvoya is a combination of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamid in one tablet.
Experimental: Phase II/Truvada Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Drug: Truvada; Truvada is intended for the treatment of HIV-1 infection. Truvada is a combination of emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in one tablet.
Experimental: Phase III/Genvoya Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Drug: Genvoya; Genvoya is a 1-pill, once-a-day prescription medicine used to treat HIV-1. Genvoya is a combination of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamid in one tablet.
Experimental: Phase III/Truvada Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Drug: Truvada; Truvada is intended for the treatment of HIV-1 infection. Truvada is a combination of emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in one tablet.

Outcome Measures

Primary Outcome Measures

1. Changes in Intracellular Emtricitabine Triphosphate (FTC-TP) [Baseline, Visit 4 (Up to ten days post drug)]

   Intracellular emtricitabine triphosphate (FTC-TP) is measured and compared from blood specimen in both arms from baseline to visit 4. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

2. Changes in Intracellular Tenofovir Diphosphate (TFV-DP) [Baseline, Visit 4 (Up to ten days post drug)]

   Intracellular tenofovir diphosphate (TFV-DP) is measured and compared from blood specimen in both arms from baseline to visit 4. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Secondary Outcome Measures

1. Change in Plasma Emtricitabine (FTC) Concentration [Baseline, Visit 4 (Up to ten days post drug)]

   Plasma emtricitabine (FTC) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

2. Change in Plasma Tenofovir Disoproxil Fumarate (TDF) Concentration [Baseline, Visit 4 (Up to ten days post drug)]

   Plasma tenofovir disoproxil fumarate (TDF) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

3. Change in Plasma Tenofovir Alafenamide (TAF) Concentration [Baseline, Visit 4 (Up to ten days post drug)]

   Plasma tenofovir alafenamide (TAF) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

4. Change in Plasma Elvitegravir (EVG) Concentration [Baseline, Visit 4 (Up to ten days post drug)]

   Plasma elvitegravir (EVG) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

5. Change in Rectal Emtricitabine (FTC) Concentration [Baseline, Visit 4 (Up to ten days post drug)]

   Emtricitabine (FTC) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

6. Change in Rectal Tenofovir Disoproxil Fumarate (TDF) Concentration [Baseline, Visit 4 (Up to ten days post drug)]

   Tenofovir disoproxil fumarate (TDF), concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

7. Change in Rectal Tenofovir Alafenamide (TAF) Concentration [Baseline, Visit 4 (Up to ten days post drug)]

   Tenofovir alafenamide (TAF) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

8. Change in Rectal Elvitegravir (EVG) Concentration [Baseline, Visit 4 (Up to ten days post drug)]

   Elvitegravir (EVG) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

9. Change in Intracellular Tenofovir Alafenamide (TAF) Concentration in Peripheral Blood Mononuclear Cells (PBMCs) [Baseline, Visit 4 (Up to ten days post drug)]

   Intracellular tenofovir alafenamide (TAF) concentration is measured from isolated PBMCs collected via blood draw. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

10. Change in Intracellular Elvitegravir (EVG) Concentration in Peripheral Blood Mononuclear Cells (PBMCs) [Baseline, Visit 4 (Up to ten days post drug)]

    Intracellular elvitegravir (EVG) concentration is measured from isolated PBMCs collected via blood draw. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

11. Change in Intracellular Emtricitabine (FTC) Concentration in Rectal Tissue [Baseline, Visit 4 (Up to ten days post drug)]

    Tissue emtricitabine (FTC) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

12. Change in Intracellular Tenofovir (TFV) Concentration in Rectal Tissue [Baseline, Visit 4 (Up to ten days post drug)]

    Intracellular tenofovir (TFV) Concentration in Rectal Tissue is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

13. Change in Tenofovir Alafenamide (TAF) Concentration in Rectal Tissue [Baseline, Visit 4 (Up to ten days post drug)]

    Tissue tenofovir alafenamide (TAF) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

14. Change in Elvitegravir (EVG) Concentration in Rectal Tissue [Baseline, Visit 4 (Up to ten days post drug)]

    Tissue elvitegravir (EVG) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

15. Change in Emtricitabine (FTC) Concentration in Penile Secretions [Baseline, Visit 4 (Up to ten days post drug)]

    Emtricitabine (FTC) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

16. Change in Tenofovir Disoproxil Fumarate (TDF) Concentration in Penile Secretions [Baseline, Visit 4 (Up to ten days post drug)]

    Tenofovir disoproxil fumarate (TDF) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

17. Change in Tenofovir Alafenamide (TAF) Concentration in Penile Secretions [Baseline, Visit 4 (Up to ten days post drug)]

    Tenofovir alafenamide (TAF) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

18. Change in Elvitegravir (EVG) Concentration in Penile Secretions [Baseline, Visit 4 (Up to ten days post drug)]

    Elvitegravir (EVG) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

19. PrEP Efficacy as Measured by Inhibition of in Vitro Infection of Rectal Biopsies to HIV [Up to 10 months post-baseline]

    Rectal biopsies will be subjected to in vitro infection with HIV to test for changes in susceptibility to virus infection. Concentrations of cumulative p24 production in supernatants following in vitro infection of rectal biopsies correlate with viral infection and replication in rectal biopsies. Therefore, lower concentrations of p24 production in biopsies collected from men receiving PrEP compared to controls indicates a potential greater protection from infection and potential increased PrEP efficacy. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

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

• Male to female transgender women who have sex with men who report receptive anal intercourse with another man in the last 6 months and are not currently taking hormonal therapy or plan to take hormonal therapy for the duration of the study

• Not currently taking PrEP and no plans to initiate during study

• Able to provide informed consent in English

• No plans for relocation in the next 3 months

• Willing to undergo peripheral blood and rectal biopsy sampling

• Willing to use study products as directed

• 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.

Exclusion Criteria:

• 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

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

1. Hgb ≤ 10 g/dL

2. PTT > 1.5x ULN or INR > 1.5x ULN

3. Platelet count <100,000

4. Creatinine clearance <60

• 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:

1. Uncontrolled or severe cardiac arrhythmia

2. Recent major abdominal, cardiothoracic, or neurological surgery

3. History of uncontrolled bleeding diathesis

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

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

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

1. Aspirin or more than 4 doses of NSAIDs

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

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

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

1. Systemic immunomodulatory agents

2. Supraphysiologic doses of steroids

3. Experimental medications, vaccines, or biologicals

• Intent to use HIV antiretroviral pre-exposure prophylaxis (PrEP) during the study, outside of the study procedures

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

• Current use of hormonal therapy

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University
• Centers for Disease Control and Prevention

Investigators

• Principal Investigator: Colleen Kelley, MD, MPH, Emory University

Study Documents (Full-Text)

• Study Protocol - Apr 21, 2017
• Statistical Analysis Plan - Jan 15, 2019

More Information

Publications

None provided.

• Responsible Party: Colleen Kelley, Assistant Professor, Emory University
• ClinicalTrials.gov Identifier: NCT02985996
• Other Study ID Numbers: IRB00092488
• First Posted: Dec 7, 2016
• Last Update Posted: Sep 17, 2019
• Last Verified: Aug 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Colleen Kelley, Assistant Professor, Emory University: Preventative Medicine; Infectious Diseases; Sexually Transmitted Diseases
• Additional relevant MeSH terms: HIV Infections; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Pre-assignment Detail	24 participants were recruited in Phase II, but only 18 were randomized to either Genvoya or Truvada due to lost to follow up. 19 participants were recruited in Phase III, but only 16 were randomized to either Genvoya or Truvada due to lost to follow up.

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to complete study phase 1. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Period Title: Overall Study
STARTED	5	8	10	7	9
COMPLETED	5	7	9	7	9
NOT COMPLETED	0	1	1	0	0

Baseline Characteristics

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada	Total
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Experimental: Phase II/Truvada Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Total of all reporting groups
Overall Participants	5	8	10	7	9	39
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	8 100%	10 100%	7 100%	9 100%	39 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	5 100%	8 100%	10 100%	7 100%	9 100%	39 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 40%	3 37.5%	7 70%	6 85.7%	4 44.4%	22 56.4%
White	3 60%	5 62.5%	2 20%	1 14.3%	4 44.4%	15 38.5%
More than one race	0 0%	0 0%	1 10%	0 0%	0 0%	1 2.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	1 11.1%	1 2.6%
Region of Enrollment (participants) [Number]
United States	5 100%	8 100%	10 100%	7 100%	9 100%	39 100%

Outcome Measures

1. Primary Outcome

Title	Changes in Intracellular Emtricitabine Triphosphate (FTC-TP)
Description	Intracellular emtricitabine triphosphate (FTC-TP) is measured and compared from blood specimen in both arms from baseline to visit 4. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [fmol/1000000 PBMC]	0	3380	2580	6470	7660

2. Primary Outcome

Title	Changes in Intracellular Tenofovir Diphosphate (TFV-DP)
Description	Intracellular tenofovir diphosphate (TFV-DP) is measured and compared from blood specimen in both arms from baseline to visit 4. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [fmol/1000000 PBMC]	0	213	28	453	80

3. Secondary Outcome

Title	Change in Plasma Emtricitabine (FTC) Concentration
Description	Plasma emtricitabine (FTC) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng/mL]	0	30	34	152	280

4. Secondary Outcome

Title	Change in Plasma Tenofovir Disoproxil Fumarate (TDF) Concentration
Description	Plasma tenofovir disoproxil fumarate (TDF) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Short Course	Phase III/Steady State	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will be randomized to receive one dose of Truvada or Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken. Truvada: Truvada is intended for the treatment of HIV-1 infection. Truvada is a combination of emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in one tablet. Genvoya: Genvoya is a 1-pill, once-a-day prescription medicine used to treat HIV-1. Genvoya is a combination of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamid in one tablet.	Participants will be randomized to receive Truvada or Genvoya to be taken once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken. Truvada: Truvada is intended for the treatment of HIV-1 infection. Truvada is a combination of emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in one tablet. Genvoya: Genvoya is a 1-pill, once-a-day prescription medicine used to treat HIV-1. Genvoya is a combination of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamid in one tablet.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng/mL]	0	0	28	0	59

5. Secondary Outcome

Title	Change in Plasma Tenofovir Alafenamide (TAF) Concentration
Description	Plasma tenofovir alafenamide (TAF) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

TAF was not measured, only the metabolite TFV was measured

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	0	0	0	0	0

6. Secondary Outcome

Title	Change in Plasma Elvitegravir (EVG) Concentration
Description	Plasma elvitegravir (EVG) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng/mL]	0	102	0	384	0

7. Secondary Outcome

Title	Change in Rectal Emtricitabine (FTC) Concentration
Description	Emtricitabine (FTC) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng/swab]	0	288	419	371	109

8. Secondary Outcome

Title	Change in Rectal Tenofovir Disoproxil Fumarate (TDF) Concentration
Description	Tenofovir disoproxil fumarate (TDF), concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng/swab]	0	58	45	533	1325

9. Secondary Outcome

Title	Change in Rectal Tenofovir Alafenamide (TAF) Concentration
Description	Tenofovir alafenamide (TAF) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

The study didn't measure TAF, only the metabolite TFV

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	0	0	0	0	0

10. Secondary Outcome

Title	Change in Rectal Elvitegravir (EVG) Concentration
Description	Elvitegravir (EVG) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng/swab]	0	405	0	219	0

11. Secondary Outcome

Title	Change in Intracellular Tenofovir Alafenamide (TAF) Concentration in Peripheral Blood Mononuclear Cells (PBMCs)
Description	Intracellular tenofovir alafenamide (TAF) concentration is measured from isolated PBMCs collected via blood draw. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

The study didn't measure TAF, only the metabolite TFV

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	0	0	0	0	0

12. Secondary Outcome

Title	Change in Intracellular Elvitegravir (EVG) Concentration in Peripheral Blood Mononuclear Cells (PBMCs)
Description	Intracellular elvitegravir (EVG) concentration is measured from isolated PBMCs collected via blood draw. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

EVG is very difficult to measure intracellularly, therefore the study only measured plasma or extracellular concentrations.

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	0	0	0	0	0

13. Secondary Outcome

Title	Change in Intracellular Emtricitabine (FTC) Concentration in Rectal Tissue
Description	Tissue emtricitabine (FTC) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [fmol/mg tissue]	0	0	0	27	41

14. Secondary Outcome

Title	Change in Intracellular Tenofovir (TFV) Concentration in Rectal Tissue
Description	Intracellular tenofovir (TFV) Concentration in Rectal Tissue is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [fmol/mg tissue]	0	17	11	0	0

15. Secondary Outcome

Title	Change in Tenofovir Alafenamide (TAF) Concentration in Rectal Tissue
Description	Tissue tenofovir alafenamide (TAF) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

The study didn't measure TAF, only the metabolite TFV

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	0	0	0	0	0

16. Secondary Outcome

Title	Change in Elvitegravir (EVG) Concentration in Rectal Tissue
Description	Tissue elvitegravir (EVG) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng/mg tissue]	0	2.7	0	6.8	0

17. Secondary Outcome

Title	Change in Emtricitabine (FTC) Concentration in Penile Secretions
Description	Emtricitabine (FTC) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Short Course	Phase III/Steady State	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will be randomized to receive one dose of Truvada or Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken. Truvada: Truvada is intended for the treatment of HIV-1 infection. Truvada is a combination of emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in one tablet. Genvoya: Genvoya is a 1-pill, once-a-day prescription medicine used to treat HIV-1. Genvoya is a combination of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamid in one tablet.	Participants will be randomized to receive Truvada or Genvoya to be taken once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken. Truvada: Truvada is intended for the treatment of HIV-1 infection. Truvada is a combination of emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in one tablet. Genvoya: Genvoya is a 1-pill, once-a-day prescription medicine used to treat HIV-1. Genvoya is a combination of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamid in one tablet.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng/swab]	0	32	30	175	54

18. Secondary Outcome

Title	Change in Tenofovir Disoproxil Fumarate (TDF) Concentration in Penile Secretions
Description	Tenofovir disoproxil fumarate (TDF) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng/swab]	0	0	0	0	17

19. Secondary Outcome

Title	Change in Tenofovir Alafenamide (TAF) Concentration in Penile Secretions
Description	Tenofovir alafenamide (TAF) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

The study did not measure TAF, only the metabolite TFV

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	0	0	0	0	0

20. Secondary Outcome

Title	Change in Elvitegravir (EVG) Concentration in Penile Secretions
Description	Elvitegravir (EVG) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Baseline, Visit 4 (Up to ten days post drug)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng/swab]	0	0	0	0	0

21. Secondary Outcome

Title	PrEP Efficacy as Measured by Inhibition of in Vitro Infection of Rectal Biopsies to HIV
Description	Rectal biopsies will be subjected to in vitro infection with HIV to test for changes in susceptibility to virus infection. Concentrations of cumulative p24 production in supernatants following in vitro infection of rectal biopsies correlate with viral infection and replication in rectal biopsies. Therefore, lower concentrations of p24 production in biopsies collected from men receiving PrEP compared to controls indicates a potential greater protection from infection and potential increased PrEP efficacy. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Time Frame	Up to 10 months post-baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Phase III/Truvada
Arm/Group Description	Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
Measure Participants	5	7	9	7	9
Median (Full Range) [ng p24]	740	225	298	348	327

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Phase I/Pre-Drug		Phase II/Genvoya		Phase II/Truvada		Phase III/Genvoya		Phase III/Truvada
Arm/Group Description	Ten participants will be asked to complete study phase 1. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.		Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.		Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.		Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.		Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.
All Cause Mortality
	Phase I/Pre-Drug		Phase II/Genvoya		Phase II/Truvada		Phase III/Genvoya		Phase III/Truvada
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/8 (0%)		0/10 (0%)		0/7 (0%)		0/9 (0%)
Serious Adverse Events
	Phase I/Pre-Drug		Phase II/Genvoya		Phase II/Truvada		Phase III/Genvoya		Phase III/Truvada
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/8 (0%)		0/10 (0%)		0/7 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Phase I/Pre-Drug		Phase II/Genvoya		Phase II/Truvada		Phase III/Genvoya		Phase III/Truvada
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/8 (0%)		0/10 (0%)		0/7 (0%)		0/9 (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.