HIV
Conditions
Keywords
Human Immunodeficiency Virus, Acquired Immune Deficiency Syndrome Virus, Pre-exposure Prophylaxis
Brief summary
The purpose of this study is to determine whether the use of rectal lubricants can affect how well the medication, Truvada, will work to prevent infection with HIV when someone is exposed to HIV in the rectum.
Detailed description
Men who have sex with men (MSM) continue to be disproportionately affected by HIV. The majority of HIV infections among MSM occur through exposure to the rectal mucosa during receptive anal intercourse (RAI). During RAI, many MSM will use lubricants, which can potentially cause mucosal inflammation and damage. A new HIV prevention intervention, called pre-exposure prophylaxis (PrEP), recommends that MSM at risk of HIV infection take a daily anti-HIV medication called Truvada (tenofovir/emtricitabine) which is highly effective. However, it is not known if the use of lubricant during RAI will interfere with the efficacy of PrEP for HIV prevention.
Interventions
DRUGTruvada
Truvada is a combination of 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate taken orally.
DEVICEGel lubricant
Five ml of an over the counter sexual lubricant will be dispensed using an applicator.
Sponsors
Centers for Disease Control and Prevention
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* HIV-negative man who reports receptive anal sex with another man in the last 6 months aged 18-49 years * Male to female transgender women who are not currently taking hormonal therapy or plan to take hormonal therapy for the duration of the study * Not currently taking pre-exposure prophylaxis (PrEP) and no plans to initiate during study * Able to provide informed consent in English * No plans for relocation in the next 6 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 study visit 2 (4-16 weeks after the screening visit)and 10 days prior to study visit 4 (5-26 weeks after the screening visit) * Willing to abstain from receptive anal intercourse for 1 week after study visit 2 (4-16 weeks after the screening visit) and study visit 4 (5-26 weeks after the screening visit)
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 for rectal biopsies, including but not limited to: 1. Hemoglobin (Hbg) ≤ 10 g/dL 2. Partial thromboplastin time (PTT) \> 1.5x upper limit normal (ULN) or international normalized ratio (INR) \> 1.5x ULN 3. Platelet count \<100,000 * 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 nonsteroidal anti-inflammatory drugs (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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Percentage of CD4 Positive T-Cells | Baseline, Post-Intervention (Day 8) | HIV target cell availability will be assessed by the median percentage of CD4+ T cells that express HIV co-receptor CCR5 as measured prior to product use and on day 8 after product use. |
| Median Cumulative Amount of p24 | Baseline, Post-Intervention (Day 8) | The median cumulative amount of p24 produced in a rectal explant challenge assay as measured by ELISA from participants prior to product use and on day 8 after product use. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Plasma Emtricitabine (FTC) Concentration | Post-Intervention (Day 8) | Median plasma FTC concentration as measured in ng/ml prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
| Median Plasma Tenofovir (TDF) Concentration | Post-Intervention (Day 8) | Median plasma TDF concentration as measured in ng/ml prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
| Median Rectal Secretion Emtricitabine (FTC) Concentration | Post-Intervention (Day 8) | Median rectal secretions FTC concentrations as measured in ng/swab prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
| Median Rectal Secretion Tenofovir (TDF) Concentration | Post-Intervention (Day 8) | Median rectal secretions TDF concentrations as measured in ng/swab prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
| Median Peripheral Blood Mononuclear Cell (PBMC) Emtricitabine (FTC) Concentration | Post-Intervention (Day 8) | Median blood PBMC FTC concentrations as measured in fmol/million cells prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
| Median Rectal Tissue Tenofovir (TDF) Concentration | Post-Intervention (Day 8) | Median rectal tissue TDF concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
| Median Rectal Tissue Deoxyadenosine Triphosphate (dATP) Concentration | Baseline, Post-Intervention (Day 8) | Median rectal tissue dATP concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
| Median Rectal Tissue Deoxycytidine Triphosphate (dCTP) Concentration | Baseline, Post-Intervention (Day 8) | Median rectal tissue dCTP concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
| Median Peripheral Blood Mononuclear Cell (PBMC) Deoxyadenosine Triphosphate (dATP) Concentration | Baseline, Post-Intervention (Day 8) | Median blood dATP concentrations as measured in fmol/million cells prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
| Median Rectal Tissue Emtricitabine (FTC) Concentration | Post-Intervention (Day 8) | Median rectal tissue FTC concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
| Median Peripheral Blood Mononuclear Cell (PBMC) Tenofovir (TDF) Concentration | Post-Intervention (Day 8) | Median blood PBMC TDF concentrations as measured in fmol/million cells prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited March 2015 through November 2016.
Pre-assignment details
Of the 86 subjects consented for study participation, 76 were randomized to a study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Rectal Gel Lubricant Subjects inserted 5 mL of lubricant in rectum for seven consecutive days
Gel lubricant: Five ml of an over the counter sexual lubricant will be dispensed using an applicator. | 20 |
| Truvada Subjects took one Truvada tablet orally for seven consecutive days
Truvada: Truvada is a combination of 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate taken orally. | 19 |
| Rectal Gel Lubricant + Truvada Subjects inserted 5 mL of lubricant in rectum and took one Truvada tablet orally for seven consecutive days
Truvada: Truvada is a combination of 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate taken orally.
Gel lubricant: Five ml of an over the counter sexual lubricant will be dispensed using an applicator. | 21 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Truvada | Rectal Gel Lubricant + Truvada | Rectal Gel Lubricant |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants | 19 Participants | 21 Participants | 20 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — |
| Region of Enrollment United States | 60 participants | 19 participants | 21 participants | 20 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 60 Participants | 19 Participants | 21 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 19 | 0 / 21 |
| other Total, other adverse events | 4 / 20 | 2 / 19 | 3 / 21 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 | 0 / 21 |
Outcome results
Primary
Median Cumulative Amount of p24
The median cumulative amount of p24 produced in a rectal explant challenge assay as measured by ELISA from participants prior to product use and on day 8 after product use.
Time frame: Baseline, Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rectal Gel Lubricant | Median Cumulative Amount of p24 | Baseline | 250 pg/mL |
| Rectal Gel Lubricant | Median Cumulative Amount of p24 | Day 8 | 363 pg/mL |
| Truvada | Median Cumulative Amount of p24 | Baseline | 287 pg/mL |
| Truvada | Median Cumulative Amount of p24 | Day 8 | 133 pg/mL |
| Rectal Gel Lubricant + Truvada | Median Cumulative Amount of p24 | Baseline | 276 pg/mL |
| Rectal Gel Lubricant + Truvada | Median Cumulative Amount of p24 | Day 8 | 284 pg/mL |
Primary
Median Percentage of CD4 Positive T-Cells
HIV target cell availability will be assessed by the median percentage of CD4+ T cells that express HIV co-receptor CCR5 as measured prior to product use and on day 8 after product use.
Time frame: Baseline, Post-Intervention (Day 8)
Population: The analysis population includes participants for whom the assay could be accurately performed. Data were not available for analysis in the case of an insufficient sample to perform this assay, poor performance of the assay, or technical issues in the laboratory.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rectal Gel Lubricant | Median Percentage of CD4 Positive T-Cells | Baseline | 62 percentage positive T-cells |
| Rectal Gel Lubricant | Median Percentage of CD4 Positive T-Cells | Day 8 | 66 percentage positive T-cells |
| Truvada | Median Percentage of CD4 Positive T-Cells | Baseline | 70 percentage positive T-cells |
| Truvada | Median Percentage of CD4 Positive T-Cells | Day 8 | 58 percentage positive T-cells |
| Rectal Gel Lubricant + Truvada | Median Percentage of CD4 Positive T-Cells | Day 8 | 51 percentage positive T-cells |
| Rectal Gel Lubricant + Truvada | Median Percentage of CD4 Positive T-Cells | Baseline | 58 percentage positive T-cells |
Secondary
Median Peripheral Blood Mononuclear Cell (PBMC) Deoxyadenosine Triphosphate (dATP) Concentration
Median blood dATP concentrations as measured in fmol/million cells prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Baseline, Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rectal Gel Lubricant | Median Peripheral Blood Mononuclear Cell (PBMC) Deoxyadenosine Triphosphate (dATP) Concentration | Baseline | 149 fmol/million cells |
| Rectal Gel Lubricant | Median Peripheral Blood Mononuclear Cell (PBMC) Deoxyadenosine Triphosphate (dATP) Concentration | Post-Intervention (Day 8) | 204 fmol/million cells |
| Truvada | Median Peripheral Blood Mononuclear Cell (PBMC) Deoxyadenosine Triphosphate (dATP) Concentration | Baseline | 140 fmol/million cells |
| Truvada | Median Peripheral Blood Mononuclear Cell (PBMC) Deoxyadenosine Triphosphate (dATP) Concentration | Post-Intervention (Day 8) | 122 fmol/million cells |
Secondary
Median Peripheral Blood Mononuclear Cell (PBMC) Emtricitabine (FTC) Concentration
Median blood PBMC FTC concentrations as measured in fmol/million cells prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rectal Gel Lubricant | Median Peripheral Blood Mononuclear Cell (PBMC) Emtricitabine (FTC) Concentration | 4980 fmol/million cells |
| Truvada | Median Peripheral Blood Mononuclear Cell (PBMC) Emtricitabine (FTC) Concentration | 4020 fmol/million cells |
Secondary
Median Peripheral Blood Mononuclear Cell (PBMC) Tenofovir (TDF) Concentration
Median blood PBMC TDF concentrations as measured in fmol/million cells prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rectal Gel Lubricant | Median Peripheral Blood Mononuclear Cell (PBMC) Tenofovir (TDF) Concentration | 45 fmol/million cells |
| Truvada | Median Peripheral Blood Mononuclear Cell (PBMC) Tenofovir (TDF) Concentration | 48 fmol/million cells |
Secondary
Median Plasma Emtricitabine (FTC) Concentration
Median plasma FTC concentration as measured in ng/ml prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rectal Gel Lubricant | Median Plasma Emtricitabine (FTC) Concentration | 248 ng/ml |
| Truvada | Median Plasma Emtricitabine (FTC) Concentration | 340 ng/ml |
Secondary
Median Plasma Tenofovir (TDF) Concentration
Median plasma TDF concentration as measured in ng/ml prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rectal Gel Lubricant | Median Plasma Tenofovir (TDF) Concentration | 52 ng/ml |
| Truvada | Median Plasma Tenofovir (TDF) Concentration | 64 ng/ml |
Secondary
Median Rectal Secretion Emtricitabine (FTC) Concentration
Median rectal secretions FTC concentrations as measured in ng/swab prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rectal Gel Lubricant | Median Rectal Secretion Emtricitabine (FTC) Concentration | 320 ng/swab |
| Truvada | Median Rectal Secretion Emtricitabine (FTC) Concentration | 382 ng/swab |
Secondary
Median Rectal Secretion Tenofovir (TDF) Concentration
Median rectal secretions TDF concentrations as measured in ng/swab prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rectal Gel Lubricant | Median Rectal Secretion Tenofovir (TDF) Concentration | 812 ng/swab |
| Truvada | Median Rectal Secretion Tenofovir (TDF) Concentration | 780 ng/swab |
Secondary
Median Rectal Tissue Deoxyadenosine Triphosphate (dATP) Concentration
Median rectal tissue dATP concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Baseline, Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rectal Gel Lubricant | Median Rectal Tissue Deoxyadenosine Triphosphate (dATP) Concentration | Baseline | 131 fmol/mg tissue |
| Rectal Gel Lubricant | Median Rectal Tissue Deoxyadenosine Triphosphate (dATP) Concentration | Post-Intervention (Day 8) | 60 fmol/mg tissue |
| Truvada | Median Rectal Tissue Deoxyadenosine Triphosphate (dATP) Concentration | Baseline | 74 fmol/mg tissue |
| Truvada | Median Rectal Tissue Deoxyadenosine Triphosphate (dATP) Concentration | Post-Intervention (Day 8) | 66 fmol/mg tissue |
Secondary
Median Rectal Tissue Deoxycytidine Triphosphate (dCTP) Concentration
Median rectal tissue dCTP concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Baseline, Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rectal Gel Lubricant | Median Rectal Tissue Deoxycytidine Triphosphate (dCTP) Concentration | Baseline | 246 fmol/mg tissue |
| Rectal Gel Lubricant | Median Rectal Tissue Deoxycytidine Triphosphate (dCTP) Concentration | Post-Intervention (Day 8) | 43 fmol/mg tissue |
| Truvada | Median Rectal Tissue Deoxycytidine Triphosphate (dCTP) Concentration | Baseline | 58 fmol/mg tissue |
| Truvada | Median Rectal Tissue Deoxycytidine Triphosphate (dCTP) Concentration | Post-Intervention (Day 8) | 36 fmol/mg tissue |
Secondary
Median Rectal Tissue Emtricitabine (FTC) Concentration
Median rectal tissue FTC concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rectal Gel Lubricant | Median Rectal Tissue Emtricitabine (FTC) Concentration | 104 fmol/mg tissue |
| Truvada | Median Rectal Tissue Emtricitabine (FTC) Concentration | 112 fmol/mg tissue |
Secondary
Median Rectal Tissue Tenofovir (TDF) Concentration
Median rectal tissue TDF concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution.
Time frame: Post-Intervention (Day 8)
Population: Number of participants who provided a viable sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rectal Gel Lubricant | Median Rectal Tissue Tenofovir (TDF) Concentration | 510 fmol/mg tissue |
| Truvada | Median Rectal Tissue Tenofovir (TDF) Concentration | 280 fmol/mg tissue |