HIV
Conditions
Brief summary
MTN-017 is a Phase 2, multi-site, randomized, six-sequence, two three-period, open label crossover study, examining the effects of oral Truvada and reduced glycerin 1% tenofovir gel. The study population will be sexually active, HIV-uninfected males who are 18 years of age or older, who report a history of receptive anal intercourse in the past 3 months. Each of the study product regimens offers different advantages to participants seeking an effective HIV prevention agent. How these relative advantages will compare in terms of safety, acceptability, systemic and local absorption, and adherence will be examined within this study.
Interventions
DRUGOral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)
DRUGRectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)
DRUGRectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Mental Health (NIMH)
National Institutes of Health (NIH)
CONRAD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Male or transgender female \> age of 18 at Screening 2. Able and willing to provide written informed consent 3. HIV-1 uninfected at Screening and Enrollment 4. Able and willing to provide adequate locator information, as defined in site SOP 5. Available to return for all study visits, barring unforeseen circumstances and willing to comply with study participation requirements 6. In general good health at Screening and Enrollment, as determined by the site IoR or designee 7. Per participant report, a history of consensual RAI at least once in the past 3 months 8. Per participant report at Screening and Enrollment, agrees not to engage in receptive or insertive sexual activity with another study participant for the duration of study participation. 9. Willing to use study-provided condoms for the duration of the study for penetrative intercourse 10. Willing to not take part in other research studies involving drugs, medical devices, vaccines or genital products for the duration of study participation (including the time between Screening and Enrollment) 11. Men and transgender females who agree to take part in the PK, PD and Mucosal Immunology Subset, must also agree to abstain from: * Inserting anything into the rectum, including abstaining from RAI for 72 hours after the collection of biopsies * Taking non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and/or other drugs that are associated with increased likelihood of bleeding following mucosal biopsy collection for 72 hours prior to and following the collection of biopsies.
Exclusion criteria
1. At Screening, participant-reported symptoms, and/or clinical or laboratory diagnosis of active anorectal or reproductive tract infection requiring treatment per current World Health Organization (WHO) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic Chlamydia trachomatis (CT) infection, Neisseria gonorrhea (GC), syphilis, active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic genital warts. Note: HSV-1 or HSV-2 seropositive diagnosis with no active lesions is allowed, since treatment is not required. In cases of non-anorectal GC/CT identified at screening, one re-screening 2 months after the screening visit will be allowed 2. History of inflammatory bowel disease as reported by participant history 3. At Screening: * Positive for hepatitis B surface antigen * Positive for hepatitis C antibody * Hemoglobin \< 10.0 g/dL * Platelet count less than 100,000/mm3 * White blood cell count \< 2,000 cells/mm3 or \> 15,000 cells/mm3 * Calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min = (140 - age in years) x (weight in kg) x (1 for male)/72 x (serum creatinine in mg/dL) * Serum creatinine \> 1.3 x the site laboratory upper limit of normal (ULN) * Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) \> 2.5× the site laboratory ULN * PK, PD and Immunological Subset only: International normalized ratio (INR) \> 1.5× the site laboratory ULN or partial thromboplastin time (PTT) \> 1.25× the site laboratory ULN 4. Known allergy to methylparaben and/or propylparaben 5. Known allergy to any of the study products. 6. Per participant report, use of the following medications and/or products within 12 weeks prior to screening, and/or anticipated use or unwillingness to abstain from use throughout study participation: * Any investigational products * Systemic immunomodulatory medications * Use of Heparin, including Lovenox® * Warfarin * Plavix® (clopidogrel bisulfate) * Rectally-administered medications or products, containing N-9 or corticosteroids 7. By participant report, use of post-exposure prophylaxis (PEP) for HIV exposure within the 12 weeks prior to screening or anticipated use during study participation. 8. Symptoms suggestive of acute HIV seroconversion at Screening and Enrollment 9. Has any other condition that, in the opinion of the Investigator of Record (IoR)/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives would make the patient unsuitable for the study or unable/unwilling to comply with the study requirements. Such conditions may include, but are not limited to, colorectal abnormalities, substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological or psychiatric disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Grade 2 or Higher Adverse Events | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | Compare the safety profiles of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Analysis of the primary endpoint of grade 2 or higher AEs was performed on only the evaluable participants based on the principle of intent-to-treat (ITT) whereby participants who were randomized were included in the analysis regardless of whether or not they received product in a given period (i.e, were lost to follow-up, or terminated early and/or were on a product hold). |
| Acceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it? | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of likelihood to use product in the future, a variable was created by combining Section N. Likelihood to Use Product in the Future of the MTN-017 Follow-up Behavioral Questionnaire questions 1A, 1B, and 1C. Categories 1 and 2 were combined and categories 3 and 4 were combined to create a dichotomous variable. |
| Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product? | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of ease of use, a variable was created to compare regimens. This variable combines questions 1A and 1BC from Section I. Ease of Use of the MTN-017 Follow-up Behavioral Questionnaire. Categories 1 and 2 were combined and categories 3 and 4 were combined to create dichotomous variables. |
| Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently? | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of liking the product, a variable was created by combining from Section H. Liking the Product of the MTN-017 Follow-up Behavioral Questionnaire question 1A and question 1BC. Categories 1 and 2 were combined and categories 3 and 4 were combined to create a dichotomous variable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | Compare tenofovir concentrations in rectal sponge specimens among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups. |
| Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | Compare tenofovir concentrations in blood plasma among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups. |
| Pharmacokinetics: End Period Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Tissue | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | Compare end period tenofovir concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups. |
| Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | Compare emtricitabine concentrations in blood plasma among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups. |
| Pharmacokinetics: End Period Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Tissue | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | Compare end period emtricitabine concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups. |
| Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | Compare emtricitabine concentrations in rectal sponge among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups. |
| Pharmacokinetics: End Period Tenofovir-Diphosphate (TFV-DP) Concentrations (log10 ng/mg) in Rectal Tissue | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | Compare end period tenofovir-diphosphate (TFV-DP) concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups. |
| Adherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | Compare percentage of prescribed doses taken orally or administered rectally in an 8-week period based on the Final Converged Rates. Final Converged Rates were measured first via self-report through Short Message Service (SMS). The clinic staff also reported the most likely number of doses taken. Finally, the MTN Behavioral Research Working Group (BRWG) provided the final estimate of the number of doses taken for each participant for each period based on self-report, staff estimates and PK testing results. Note that these final judgement data are missing if PK results are missing. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Product Sharing | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | To determine the level of sharing of study products with non-participants and to assess with whom products are shared |
| Problem Practices | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | To determine the prevalence of behavioral practices associated with anal intercourse that may affect microbicide use |
| Factors Associated With Adherence | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | To identify factors associated with product adherence and whether they differ by product used (FTC/TDF or TFV RG 1% gel) or regimen (daily use or RAI-associated use) |
| Correlation Between PK and Adherence | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | To assess correlation of PK with adherence measures |
| Pharmacodynamics | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | To characterize pharmacodynamic responses following oral and rectal exposure to antiretroviral drugs |
| Mucosal Immunity | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | To characterize changes in mucosal immunity between baseline and the end of the daily FTC/TDF and TFV RG 1% gel product use |
| Sexual Activity and Condom Use | 27 weeks (three 8-week product use periods with 1-week washout periods between them) | To examine whether sexual activity or condom use varies by product used |
Countries
Peru, Puerto Rico, South Africa, Thailand, United States
Participant flow
Recruitment details
HIV-uninfected males or transgender females who were 18 years of age or older who practice receptive anal intercourse were recruited from September 2013 through November 2014 from 8 sites in Peru, Puerto Rico, South Africa, Thailand and USA.
Pre-assignment details
349 persons were screened and 154 were excluded for various reasons. The study enrolled 195 participants, 187 of whom are evaluable. Evaluable participants are those participants who were enrolled and not replaced, or were the final enrolled replacement participant for another enrolled participant who met the criteria for replacement.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)
Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)
Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)
Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel) | 33 |
| Group 2 Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)
Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)
Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)
Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel) | 32 |
| Group 3 Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks)
Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)
Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)
Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel) | 31 |
| Group 4 Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)
Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)
Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)
Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel) | 34 |
| Group 5 Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)
Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)
Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)
Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel) | 33 |
| Group 6 Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks);followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks)
Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)
Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)
Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel) | 32 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Relocated, no follow-up planned | 1 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Total | Group 1 |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 30.4 years STANDARD_DEVIATION 10.6 | 32.4 years STANDARD_DEVIATION 9.2 | 29.6 years STANDARD_DEVIATION 8.9 | 32.2 years STANDARD_DEVIATION 10.6 | 31.4 years STANDARD_DEVIATION 7.8 | 31.1 years STANDARD_DEVIATION 9.3 | 30.9 years STANDARD_DEVIATION 8.5 |
| Age, Customized 20-24 | 7 participants | 6 participants | 12 participants | 7 participants | 5 participants | 44 participants | 7 participants |
| Age, Customized 25-29 | 11 participants | 6 participants | 6 participants | 7 participants | 6 participants | 43 participants | 7 participants |
| Age, Customized 30-34 | 4 participants | 6 participants | 7 participants | 7 participants | 10 participants | 40 participants | 6 participants |
| Age, Customized 35-39 | 4 participants | 2 participants | 2 participants | 2 participants | 4 participants | 20 participants | 6 participants |
| Age, Customized 40-44 | 3 participants | 4 participants | 3 participants | 3 participants | 2 participants | 19 participants | 4 participants |
| Age, Customized 45-49 | 0 participants | 4 participants | 2 participants | 2 participants | 3 participants | 11 participants | 0 participants |
| Age, Customized 50+ | 2 participants | 1 participants | 1 participants | 3 participants | 0 participants | 8 participants | 1 participants |
| Age, Customized Under 20 | 1 participants | 2 participants | 1 participants | 2 participants | 2 participants | 10 participants | 2 participants |
| Highest Level of Education attended college or university | 26 participants | 23 participants | 28 participants | 26 participants | 24 participants | 156 participants | 29 participants |
| Highest Level of Education no schooling | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Highest Level of Education primary school, complete | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 2 participants | 0 participants |
| Highest Level of Education primary school, not complete | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Highest Level of Education secondary school, complete | 5 participants | 6 participants | 4 participants | 4 participants | 6 participants | 27 participants | 2 participants |
| Highest Level of Education secondary school, not complete | 1 participants | 1 participants | 1 participants | 3 participants | 1 participants | 9 participants | 2 participants |
| Hispanic Origin No | 23 participants | 23 participants | 26 participants | 21 participants | 24 participants | 140 participants | 23 participants |
| Hispanic Origin Yes | 9 participants | 8 participants | 8 participants | 12 participants | 8 participants | 55 participants | 10 participants |
| Nationality Peru | 6 participants | 6 participants | 6 participants | 7 participants | 6 participants | 38 participants | 7 participants |
| Nationality Puerto Rico | 1 participants | 1 participants | 1 participants | 2 participants | 1 participants | 7 participants | 1 participants |
| Nationality South Africa | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 18 participants | 3 participants |
| Nationality Thailand | 9 participants | 9 participants | 9 participants | 9 participants | 9 participants | 54 participants | 9 participants |
| Nationality U.S.A. | 13 participants | 12 participants | 15 participants | 12 participants | 13 participants | 78 participants | 13 participants |
| Race - Peru Asian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - Peru Black | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - Peru Indigenous | 3 participants | 3 participants | 1 participants | 4 participants | 1 participants | 13 participants | 1 participants |
| Race - Peru Mixed | 3 participants | 3 participants | 4 participants | 3 participants | 5 participants | 24 participants | 6 participants |
| Race - Peru Other | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - Peru White | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race - Puerto Rico Asian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - Puerto Rico Black | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 2 participants | 0 participants |
| Race - Puerto Rico Indigenous | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - Puerto Rico Mixed | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 2 participants | 0 participants |
| Race - Puerto Rico Other | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race - Puerto Rico White | 0 participants | 0 participants | 0 participants | 2 participants | 0 participants | 2 participants | 0 participants |
| Race - South Africa Colored | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants |
| Race - South Africa Indian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - South Africa Other | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race - South Africa Other African tribe | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants | 2 participants | 0 participants |
| Race - South Africa White | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - South Africa Xhosa | 2 participants | 3 participants | 2 participants | 3 participants | 1 participants | 14 participants | 3 participants |
| Race - South Africa Zulu | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - Thailand Chinese | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - Thailand Indian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - Thailand Mixed | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - Thailand Other | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - Thailand Thai | 9 participants | 9 participants | 9 participants | 9 participants | 9 participants | 54 participants | 9 participants |
| Race - U.S.A. American Indian/Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - U.S.A. Asian | 0 participants | 0 participants | 0 participants | 2 participants | 2 participants | 4 participants | 0 participants |
| Race - U.S.A. Black/African-American | 0 participants | 0 participants | 3 participants | 0 participants | 0 participants | 3 participants | 0 participants |
| Race - U.S.A. Mixed | 0 participants | 0 participants | 0 participants | 2 participants | 0 participants | 2 participants | 0 participants |
| Race - U.S.A. Native-Hawaiian or other Pacific Islander | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race - U.S.A. Other | 2 participants | 2 participants | 0 participants | 2 participants | 1 participants | 8 participants | 1 participants |
| Race - U.S.A. White | 11 participants | 10 participants | 12 participants | 6 participants | 10 participants | 61 participants | 12 participants |
| Sex/Gender, Customized Man | 21 participants | 22 participants | 27 participants | 26 participants | 24 participants | 141 participants | 21 participants |
| Sex/Gender, Customized Other | 4 participants | 6 participants | 3 participants | 3 participants | 6 participants | 27 participants | 5 participants |
| Sex/Gender, Customized Refuse to answer | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 3 participants | 2 participants |
| Sex/Gender, Customized Transgender/Transwoman | 6 participants | 2 participants | 3 participants | 3 participants | 1 participants | 19 participants | 4 participants |
| Sex/Gender, Customized Woman | 0 participants | 1 participants | 1 participants | 1 participants | 1 participants | 4 participants | 0 participants |
| Sexual Orientation (CASI) Bisexual | 3 participants | 3 participants | 0 participants | 3 participants | 1 participants | 13 participants | 3 participants |
| Sexual Orientation (CASI) Gay/Homosexual | 26 participants | 27 participants | 32 participants | 28 participants | 31 participants | 171 participants | 27 participants |
| Sexual Orientation (CASI) Other | 1 participants | 0 participants | 1 participants | 2 participants | 0 participants | 5 participants | 1 participants |
| Sexual Orientation (CASI) Refuse to answer | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants | 1 participants |
| Sexual Orientation (CASI) Straight/Heterosexual | 1 participants | 1 participants | 1 participants | 0 participants | 0 participants | 3 participants | 0 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 85 / 192 | 103 / 192 | 87 / 191 |
| serious Total, serious adverse events | 1 / 192 | 2 / 192 | 0 / 191 |
Outcome results
Primary
Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product?
To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of ease of use, a variable was created to compare regimens. This variable combines questions 1A and 1BC from Section I. Ease of Use of the MTN-017 Follow-up Behavioral Questionnaire. Categories 1 and 2 were combined and categories 3 and 4 were combined to create dichotomous variables.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: All primary analyses are based on the data from evaluable participants. Evaluable participants are those participants who were enrolled and not replaced, or were the final enrolled replacement participant for another enrolled participant who met the criteria for replacement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Product 1 | Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product? | Very Difficult/Difficult | 14 participants |
| Product 1 | Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product? | Very Easy/Easy | 169 participants |
| Product 2 | Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product? | Very Difficult/Difficult | 24 participants |
| Product 2 | Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product? | Very Easy/Easy | 160 participants |
| Product 3 | Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product? | Very Difficult/Difficult | 18 participants |
| Product 3 | Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product? | Very Easy/Easy | 165 participants |
Comparison: Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.p-value: 0.0895% CI: [0.29, 1.08]Generalized Estimating Equation (GEE)
Comparison: Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.p-value: 0.4695% CI: [0.37, 1.56]Generalized Estimating Equation (GEE)
Primary
Acceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it?
To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of likelihood to use product in the future, a variable was created by combining Section N. Likelihood to Use Product in the Future of the MTN-017 Follow-up Behavioral Questionnaire questions 1A, 1B, and 1C. Categories 1 and 2 were combined and categories 3 and 4 were combined to create a dichotomous variable.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: All primary analyses are based on the data from evaluable participants. Evaluable participants are those participants who were enrolled and not replaced, or were the final enrolled replacement participant for another enrolled participant who met the criteria for replacement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Product 1 | Acceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it? | Very Unlikely/Unlikely | 24 participants |
| Product 1 | Acceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it? | Very Likely/Likely | 159 participants |
| Product 2 | Acceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it? | Very Unlikely/Unlikely | 52 participants |
| Product 2 | Acceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it? | Very Likely/Likely | 132 participants |
| Product 3 | Acceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it? | Very Unlikely/Unlikely | 31 participants |
| Product 3 | Acceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it? | Very Likely/Likely | 145 participants |
Comparison: Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.p-value: 0.000495% CI: [0.22, 0.65]Generalized Estimating Equation (GEE)
Comparison: Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.p-value: 0.2395% CI: [0.39, 1.25]Generalized Estimating Equation (GEE)
Primary
Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently?
To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of liking the product, a variable was created by combining from Section H. Liking the Product of the MTN-017 Follow-up Behavioral Questionnaire question 1A and question 1BC. Categories 1 and 2 were combined and categories 3 and 4 were combined to create a dichotomous variable.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: All primary analyses are based on the data from evaluable participants. Evaluable participants are those participants who were enrolled and not replaced, or were the final enrolled replacement participant for another enrolled participant who met the criteria for replacement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Product 1 | Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently? | Disliked Very Much/A Little | 16 participants |
| Product 1 | Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently? | Liked Very Much/A Little | 163 participants |
| Product 2 | Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently? | Disliked Very Much/A Little | 47 participants |
| Product 2 | Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently? | Liked Very Much/A Little | 134 participants |
| Product 3 | Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently? | Disliked Very Much/A Little | 38 participants |
| Product 3 | Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently? | Liked Very Much/A Little | 145 participants |
Comparison: Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.p-value: <0.000195% CI: [0.15, 0.5]Generalized Estimating Equation (GEE)
Comparison: Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.p-value: 0.00295% CI: [0.2, 0.7]Generalized Estimating Equation (GEE)
Primary
Safety: Grade 2 or Higher Adverse Events
Compare the safety profiles of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Analysis of the primary endpoint of grade 2 or higher AEs was performed on only the evaluable participants based on the principle of intent-to-treat (ITT) whereby participants who were randomized were included in the analysis regardless of whether or not they received product in a given period (i.e, were lost to follow-up, or terminated early and/or were on a product hold).
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: Among the 187 evaluable participants. One participant was terminated before the Initiate Period visit of his/her Period 3 (Oral Tablet regimen period). Thus, this participant is removed from the analysis of the oral period regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Product 1 | Safety: Grade 2 or Higher Adverse Events | 64 participants |
| Product 2 | Safety: Grade 2 or Higher Adverse Events | 61 participants |
| Product 3 | Safety: Grade 2 or Higher Adverse Events | 56 participants |
Comparison: Since some participants have more than one safety event per period of treatment regimen, a Generalized Estimating Equation (GEE) model with a Poisson (log) link, exchangeable correlation structure, and robust standard errors were used.p-value: 0.8895% CI: [0.73, 1.44]Generalized Estimating Equation (GEE)
Comparison: Since some participants have more than one safety event per period of treatment regimen, a Generalized Estimating Equation (GEE) model with a Poisson (log) link, exchangeable correlation structure, and robust standard errors were used.p-value: 0.4395% CI: [0.64, 1.21]Generalized Estimating Equation (GEE)
Secondary
Adherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period
Compare percentage of prescribed doses taken orally or administered rectally in an 8-week period based on the Final Converged Rates. Final Converged Rates were measured first via self-report through Short Message Service (SMS). The clinic staff also reported the most likely number of doses taken. Finally, the MTN Behavioral Research Working Group (BRWG) provided the final estimate of the number of doses taken for each participant for each period based on self-report, staff estimates and PK testing results. Note that these final judgement data are missing if PK results are missing.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: Evaluable participants with Final Converged Rates of prescribed doses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Product 1 | Adherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period | Less Than 80% | 12 Participants |
| Product 1 | Adherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period | At or Greater than 80% | 173 Participants |
| Product 2 | Adherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period | At or Greater than 80% | 153 Participants |
| Product 2 | Adherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period | Less Than 80% | 31 Participants |
| Product 3 | Adherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period | Less Than 80% | 13 Participants |
| Product 3 | Adherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period | At or Greater than 80% | 170 Participants |
Comparison: Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables was used to compare the three treatment regimens for the acceptability endpoints. Because the distribution of the adherence percentages were skewed, we did not use a linear mixed effects model as originally planned. Instead, we dichotomized the adherence percentage into\<80% adherence versus\>80% adherence.p-value: 0.000595% CI: [0.19, 0.63]Generalized Estimating Equations (GEE)
Comparison: Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables was used to compare the three treatment regimens for the acceptability endpoints. Because the distribution of the adherence percentages were skewed, we did not use a linear mixed effects model as originally planned. Instead, we dichotomized the adherence percentage into\<80% adherence versus\>80% adherence.p-value: 0.7495% CI: [0.43, 1.81]Generalized Estimating Equations (GEE)
Secondary
Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge
Compare emtricitabine concentrations in rectal sponge among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: Participant periods with emtricitabine (FTC) concentrations (log10 ng/mg) in rectal sponge specimens among evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product 1 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge | Mid-Period FTC Concentration | 0.31 log10 ng/mg | Standard Deviation 1.14 |
| Product 1 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge | Initiate Period FTC Concentration | -1.75 log10 ng/mg | Standard Deviation 0.8 |
| Product 1 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge | End Period FTC Concentration | 0.14 log10 ng/mg | Standard Deviation 1.3 |
| Product 2 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge | Mid-Period FTC Concentration | -1.76 log10 ng/mg | Standard Deviation 0.76 |
| Product 2 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge | Initiate Period FTC Concentration | -1.76 log10 ng/mg | Standard Deviation 0.73 |
| Product 2 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge | End Period FTC Concentration | -1.80 log10 ng/mg | Standard Deviation 0.69 |
| Product 3 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge | Initiate Period FTC Concentration | -1.57 log10 ng/mg | Standard Deviation 1 |
| Product 3 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge | End Period FTC Concentration | -1.69 log10 ng/mg | Standard Deviation 0.87 |
| Product 3 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge | Mid-Period FTC Concentration | -1.67 log10 ng/mg | Standard Deviation 0.91 |
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality. Mid period and end period visits only are used in this analysis.p-value: <0.00195% CI: [-2.16, -1.84]Mixed Models Analysis
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality. Mid period and end period visits only are used in this analysis.p-value: <0.00195% CI: [-2.07, -1.74]Mixed Models Analysis
Secondary
Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma
Compare emtricitabine concentrations in blood plasma among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: Participant periods with emtricitabine (FTC) concentrations (log10 ng/mL) in blood plasma among evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product 1 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma | Mid-Period FTC Concentration | 2.34 log10 ng/mL | Standard Deviation 0.82 |
| Product 1 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma | End Period FTC Concentration | 2.25 log10 ng/mL | Standard Deviation 0.96 |
| Product 2 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma | Mid-Period FTC Concentration | -0.35 log10 ng/mL | Standard Deviation 1 |
| Product 2 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma | End Period FTC Concentration | -0.37 log10 ng/mL | Standard Deviation 0.98 |
| Product 3 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma | Mid-Period FTC Concentration | -0.37 log10 ng/mL | Standard Deviation 0.98 |
| Product 3 | Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma | End Period FTC Concentration | -0.33 log10 ng/mL | Standard Deviation 1.06 |
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality for the following analysis.p-value: <0.00195% CI: [-2.82, -2.5]Mixed Models Analysis
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality for the following analysis.p-value: <0.00195% CI: [-2.81, -2.49]Mixed Models Analysis
Secondary
Pharmacokinetics: End Period Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Tissue
Compare end period emtricitabine concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: Participant end periods with emtricitabine (FTC) concentrations (log10 ng/mg) in rectal tissue among evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product 1 | Pharmacokinetics: End Period Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Tissue | -0.35 log10 ng/mg | Standard Deviation 0.33 |
| Product 2 | Pharmacokinetics: End Period Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Tissue | -1.26 log10 ng/mg | Standard Deviation 0 |
| Product 3 | Pharmacokinetics: End Period Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Tissue | -1.26 log10 ng/mg | Standard Deviation 0 |
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality. End period visits only are used in this analysis.p-value: <0.00195% CI: [-1.01, -0.8]Mixed Models Analysis
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality. End period visits only are used in this analysis.p-value: <0.00195% CI: [-1.01, -0.8]Mixed Models Analysis
Secondary
Pharmacokinetics: End Period Tenofovir-Diphosphate (TFV-DP) Concentrations (log10 ng/mg) in Rectal Tissue
Compare end period tenofovir-diphosphate (TFV-DP) concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: Participant end periods with tenofovir-diphosphate (TFV-DP) concentrations (log10 ng/mg) in rectal tissue among evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product 1 | Pharmacokinetics: End Period Tenofovir-Diphosphate (TFV-DP) Concentrations (log10 ng/mg) in Rectal Tissue | 1.52 log10 ng/mg | Standard Deviation 0.5 |
| Product 2 | Pharmacokinetics: End Period Tenofovir-Diphosphate (TFV-DP) Concentrations (log10 ng/mg) in Rectal Tissue | 2.06 log10 ng/mg | Standard Deviation 0.52 |
| Product 3 | Pharmacokinetics: End Period Tenofovir-Diphosphate (TFV-DP) Concentrations (log10 ng/mg) in Rectal Tissue | 1.54 log10 ng/mg | Standard Deviation 0.92 |
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality.p-value: <0.00195% CI: [0.35, 0.72]Mixed Models Analysis
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality.p-value: 0.9295% CI: [-0.28, 0.31]Mixed Models Analysis
Secondary
Pharmacokinetics: End Period Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Tissue
Compare end period tenofovir concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: Participant end periods with tenofovir concentrations (log10 ng/mg) in rectal tissue among evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product 1 | Pharmacokinetics: End Period Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Tissue | 0.18 log10 ng/mg | Standard Deviation 0.51 |
| Product 2 | Pharmacokinetics: End Period Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Tissue | 0.84 log10 ng/mg | Standard Deviation 0.5 |
| Product 3 | Pharmacokinetics: End Period Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Tissue | 0.02 log10 ng/mg | Standard Deviation 0.87 |
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality.p-value: <0.00195% CI: [0.49, 0.83]Mixed Models Analysis
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality.p-value: 0.3195% CI: [-0.46, 0.15]Mixed Models Analysis
Secondary
Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge
Compare tenofovir concentrations in rectal sponge specimens among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: Participant periods with tenofovir concentrations (log10 ng/mg) in rectal sponge specimens among evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product 1 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge | Mid-Period TFV Concentration | 0.71 log10 ng/mg | Standard Deviation 1.22 |
| Product 1 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge | Initiate Period TFV Concentration | -1.53 log10 ng/mg | Standard Deviation 1.2 |
| Product 1 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge | End Period TFV Concentration | 0.66 log10 ng/mg | Standard Deviation 1.31 |
| Product 2 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge | Mid-Period TFV Concentration | 0.97 log10 ng/mg | Standard Deviation 1.64 |
| Product 2 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge | Initiate Period TFV Concentration | -1.65 log10 ng/mg | Standard Deviation 1.12 |
| Product 2 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge | End Period TFV Concentration | 1.00 log10 ng/mg | Standard Deviation 1.42 |
| Product 3 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge | Initiate Period TFV Concentration | -1.29 log10 ng/mg | Standard Deviation 1.42 |
| Product 3 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge | End Period TFV Concentration | 0.01 log10 ng/mg | Standard Deviation 1.67 |
| Product 3 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge | Mid-Period TFV Concentration | -0.03 log10 ng/mg | Standard Deviation 1.54 |
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality. Mid period and end period visits only were used in this analysis.p-value: 0.00495% CI: [0.1, 0.5]Mixed Models Analysis
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality.p-value: <0.00195% CI: [-0.92, -0.47]Mixed Models Analysis
Secondary
Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma
Compare tenofovir concentrations in blood plasma among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Population: Participant periods with tenofovir concentrations (log10 ng/mL) in blood plasma among evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product 1 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma | Mid-Period TFV Concentration | 1.85 log10 ng/mL | Standard Deviation 0.59 |
| Product 1 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma | End Period TFV Concentration | 1.77 log10 ng/mL | Standard Deviation 0.71 |
| Product 2 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma | Mid-Period TFV Concentration | 0.42 log10 ng/mL | Standard Deviation 0.83 |
| Product 2 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma | End Period TFV Concentration | 0.37 log10 ng/mL | Standard Deviation 0.84 |
| Product 3 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma | Mid-Period TFV Concentration | -0.01 log10 ng/mL | Standard Deviation 0.89 |
| Product 3 | Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma | End Period TFV Concentration | -0.02 log10 ng/mL | Standard Deviation 0.92 |
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality.p-value: <0.00195% CI: [-1.53, -1.3]Mixed Models Analysis
Comparison: Mixed effects models were used to compare the three treatment regimens within participants over time using the oral regimen as the reference group. The models included fixed effects for treatment regimen and period and random effects for participant within sequence. The log 10 transformation was used in the mixed effects models for all PK results to achieve normality.p-value: <0.00195% CI: [-1.95, -1.7]Mixed Models Analysis
Other Pre-specified
Correlation Between PK and Adherence
To assess correlation of PK with adherence measures
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Other Pre-specified
Factors Associated With Adherence
To identify factors associated with product adherence and whether they differ by product used (FTC/TDF or TFV RG 1% gel) or regimen (daily use or RAI-associated use)
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Other Pre-specified
Mucosal Immunity
To characterize changes in mucosal immunity between baseline and the end of the daily FTC/TDF and TFV RG 1% gel product use
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Other Pre-specified
Pharmacodynamics
To characterize pharmacodynamic responses following oral and rectal exposure to antiretroviral drugs
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Other Pre-specified
Problem Practices
To determine the prevalence of behavioral practices associated with anal intercourse that may affect microbicide use
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Other Pre-specified
Product Sharing
To determine the level of sharing of study products with non-participants and to assess with whom products are shared
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Other Pre-specified
Sexual Activity and Condom Use
To examine whether sexual activity or condom use varies by product used
Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)