Human Immunodeficiency Virus (HIV) Prophylaxis
Conditions
Keywords
TDF, FTC, MVC, TDF-FTC, TDF-FTC-MVC, IVR, ARV
Brief summary
This study will evaluate the hypothesis that intravaginal rings (IVRs) can safely and in a sustained fashion, deliver the antiretroviral (ARV) drugs - tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and maraviroc (MVC), in healthy women when used in the following drug combinations: 1) TDF (Single IVR); 2) TDF-FTC (Dual IVR) and; 3) TDF-FTC-MVC (Triple IVR). TDF = tenofovir disoproxil fumarate; FTC = emtrcitabine; MVC = maraviroc
Detailed description
The broad long term goal of this project is to empower women to protect themselves from HIV through woman-controlled sustained local delivery of ARTs via intravaginal rings. The short-term general investigational plan is to evaluate IVRs releasing TDF, TDF-FTC and TDF-FTC-MVC in healthy women for up to 7 days in an open-label study to determine safety and drug concentrations in plasma and cervicovaginal lavage and secretions. Additional exploratory studies will be considered and planned based in part on the results obtained in this study. The long-term investigational plan is to evaluate the safety and efficacy of sustained release TDF, TDF-FTC and TDF-FTC-MVC for their ability to decrease HIV transmission to vulnerable women.
Interventions
DRUGTDF IVR
DRUGTDF-FTC IVR
DRUGTDF-FTC-MVC IVR
Sponsors
The University of Texas Medical Branch, Galveston
Oak Crest Institute of Science
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Auritec Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Provides written informed consent * Healthy female 18-45 years of age * HIV negative per subject report and results of screening examination * Negative for sexually transmitted diseases in the past 3 months and at screening exam * No history of genital herpes simplex I or II per subject report * Currently using contraception with plans to continue throughout the study duration or having sex with females only * Pre-menopausal with a regular menstrual cycle with at least 21 days between menses and no history of intermenstrual bleeding or with suppressed menstrual cycle by hormonal contraception such as Depo-Provera or continuous oral contraceptive agents * Subjects must agree to abstain from vaginal, anal, and oral sex throughout the first week of each dosing period and then use condoms for vaginal/rectal intercourse until after the final visit for use of each IVR * Subjects must agree to not douche or use any vaginal product other than the Single, Dual and Triple ARV IVRs, including lubricants, feminine hygiene products, and vaginal drying agents throughout the dosing period and until after the final visit * Subjects must agree to blood draws and vaginal exams throughout the course of the study
Exclusion criteria
* HIV positive by subject report or results of screening examination * Positive history for autoimmune disease * Abnormal genital exam defined as grade 1 or higher adverse event by DAIDS genital AE grading table * Abnormal ALT or AST or Hepatitis B infection * Active vaginal infection as determined by site IoR * Abnormal renal function (defined as a creatinine clearance of \<50mL/min/1.73 m2) * Pregnant or less than 6 months post-partum or current lactation * Current use of an IVR (i.e., Nuvaring, Estring, Femring) * History of TDF, FTC, and MVC use and/or adverse reaction to any of these drugs * History of adverse reaction to silicone * History of toxic shock syndrome * Currently receiving chemotherapy or immunosuppressive agents * Use of investigative drugs within 30 days or 5 half-lives * Currently using or suspected to be using non-therapeutic injection drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Lavage (CVL) | Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). | Drug concentrations \[tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)\] in cervicovaginal lavage (CVL) were evaluated for each IVR combination. |
| Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Days 0-21 following insertion of each IVR. | Number of Adverse Events (AEs) was recorded. Safety parameters were monitored for each IVR combination and the grading scale for each parameter followed the Female Genital Grading Table for Use in Microbicide Studies. AEs not included in that table were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014 (Grade 1 = mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life-Threatening). |
| Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). | Drug concentrations \[tenofovir (TFV), tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)\] in cervicovaginal fluids (CVF) for each IVR combination. |
| Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | Time points at which outcome measure was assessed are Day 7 (day of IVR removal) and daily up to 14 days. | Drug concentrations \[tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)\] in terminal half-life were evaluated for each IVR combination. |
| Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). | Drug concentrations \[tenofovir disoproxil fumarate (TDF), tenofovir (TFV), tenofovir diphosphate (TFV-DP), emtricitabine (FTC) and maraviroc (MVC)\] in vaginal tissue (VT) were evaluated for each IVR combination. |
| Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). | Drug concentrations \[tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)\] in plasma were evaluated for each IVR combination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acceptability of the IVRs | Days 0-21 following insertion of each IVR. | Acceptability of the IVRs was assessed through reported willingness to use the IVR for 28 days in a real-world setting on a likert scale, 1 being not at all confident to 5 being completely confident for Periods 1 and 2. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All subjects will be asked to wear Single (TDF) IVRs for 7 days.
If the TDF IVR is determined as safe, study participants will be asked to replace it with Dual (TDF-FTC) IVRs for 7 days. There will be follow-up visit between removal of a single IVR and replacing it with a dual IVR.
If the TDF-FTC IVR is determined as safe, study participants will be asked to replace them with Triple (TDF-FTC-MVC) IVRs for 7 days. There will be follow-up visit between removal of a dual IVR and replacing it with a triple IVR. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous Period 1 and Period 2 | 26 years |
| Age, Continuous Period 3 | 24.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs)
Number of Adverse Events (AEs) was recorded. Safety parameters were monitored for each IVR combination and the grading scale for each parameter followed the Female Genital Grading Table for Use in Microbicide Studies. AEs not included in that table were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014 (Grade 1 = mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life-Threatening).
Time frame: Days 0-21 following insertion of each IVR.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Malaise: Grade 1 | 1 participants |
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Vulvovaginal Itching: Grade 1 | 3 participants |
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Nausea: Grade 1 | 0 participants |
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Diarrhea: Grade 1 | 1 participants |
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Cervicovaginal Erythema: Grade 1 | 3 participants |
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Pelvic Pain: Grade 1 | 4 participants |
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Vaginal Discharge: Grade 1 | 3 participants |
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Pelvic Pain: Grade 2 | 1 participants |
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Odor: Grade 1 | 0 participants |
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Metrorrhagia: Grade 1 | 1 participants |
| Period 1: TDF (Single IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Candida (monilial vulvovaginitis): Grade 2 | 0 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Cervicovaginal Erythema: Grade 1 | 1 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Pelvic Pain: Grade 1 | 1 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Pelvic Pain: Grade 2 | 1 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Vaginal Discharge: Grade 1 | 3 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Metrorrhagia: Grade 1 | 0 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Vulvovaginal Itching: Grade 1 | 0 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Diarrhea: Grade 1 | 0 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Malaise: Grade 1 | 0 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Odor: Grade 1 | 0 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Nausea: Grade 1 | 0 participants |
| Period 2: TDF-FTC (Dual IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Candida (monilial vulvovaginitis): Grade 2 | 0 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Nausea: Grade 1 | 1 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Malaise: Grade 1 | 0 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Vaginal Discharge: Grade 1 | 1 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Pelvic Pain: Grade 1 | 4 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Odor: Grade 1 | 1 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Pelvic Pain: Grade 2 | 0 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Cervicovaginal Erythema: Grade 1 | 0 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Vulvovaginal Itching: Grade 1 | 1 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Candida (monilial vulvovaginitis): Grade 2 | 1 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Diarrhea: Grade 1 | 0 participants |
| Period 3: TDF-FTC-MVC (Triple IVR) | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Metrorrhagia: Grade 1 | 2 participants |
Primary
Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF)
Drug concentrations \[tenofovir (TFV), tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)\] in cervicovaginal fluids (CVF) for each IVR combination.
Time frame: Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | emtricitabine | NA ng/mg |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | Total tenofovir | 36.2 ng/mg |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | tenofovir disoproxil fumarate | 58.1 ng/mg |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | tenofovir | 13.9 ng/mg |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | maraviroc | NA ng/mg |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | Total tenofovir | 34.4 ng/mg |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | tenofovir disoproxil fumarate | 43.1 ng/mg |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | tenofovir | 15.9 ng/mg |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | emtricitabine | 896 ng/mg |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | maraviroc | NA ng/mg |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | maraviroc | 429.8 ng/mg |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | emtricitabine | 838.5 ng/mg |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | tenofovir disoproxil fumarate | 96.9 ng/mg |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | Total tenofovir | 70.0 ng/mg |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | tenofovir | 28.0 ng/mg |
Primary
Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Lavage (CVL)
Drug concentrations \[tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)\] in cervicovaginal lavage (CVL) were evaluated for each IVR combination.
Time frame: Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Lavage (CVL) | tenofovir disoproxil fumarate | 1,930 ng/mL |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Lavage (CVL) | tenofovir | 611 ng/mL |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Lavage (CVL) | tenofovir disoproxil fumarate | 1,720 ng/mL |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Lavage (CVL) | tenofovir | 927 ng/mL |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Lavage (CVL) | tenofovir disoproxil fumarate | 3,630 ng/mL |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Lavage (CVL) | tenofovir | 2,670 ng/mL |
Primary
Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma
Drug concentrations \[tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)\] in plasma were evaluated for each IVR combination.
Time frame: Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | emtricitabine: Plasma | NA ng/mL |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | tenofovir: Plasma | NA ng/mL |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | maraviroc: Plasma | NA ng/mL |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | emtricitabine: Plasma | 0.95 ng/mL |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | tenofovir: Plasma | NA ng/mL |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | maraviroc: Plasma | NA ng/mL |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | tenofovir: Plasma | NA ng/mL |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | maraviroc: Plasma | 0.08 ng/mL |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | emtricitabine: Plasma | 1.02 ng/mL |
Primary
Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life
Drug concentrations \[tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)\] in terminal half-life were evaluated for each IVR combination.
Time frame: Time points at which outcome measure was assessed are Day 7 (day of IVR removal) and daily up to 14 days.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | tenofovir disoproxil fumarate: Terminal Half-life | 11.8 Hour |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | tenofovir: Terminal Half-life | 39.5 Hour |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | emtricitabine: Terminal Half-life | NA Hour |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | maraviroc: Terminal Half-life | NA Hour |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | maraviroc: Terminal Half-life | NA Hour |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | tenofovir disoproxil fumarate: Terminal Half-life | 14.2 Hour |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | emtricitabine: Terminal Half-life | 19.1 Hour |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | tenofovir: Terminal Half-life | 31.4 Hour |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | maraviroc: Terminal Half-life | 16.0 Hour |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | tenofovir: Terminal Half-life | 24.8 Hour |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | emtricitabine: Terminal Half-life | 17.0 Hour |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | tenofovir disoproxil fumarate: Terminal Half-life | 18.3 Hour |
Primary
Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue
Drug concentrations \[tenofovir disoproxil fumarate (TDF), tenofovir (TFV), tenofovir diphosphate (TFV-DP), emtricitabine (FTC) and maraviroc (MVC)\] in vaginal tissue (VT) were evaluated for each IVR combination.
Time frame: Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | tenofovir | 8.4 ng/mg |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | tenofovir diphosphate | 303 ng/mg |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | emtricitabine | NA ng/mg |
| Period 1: TDF (Single IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | maraviroc | NA ng/mg |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | maraviroc | NA ng/mg |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | tenofovir | 5.1 ng/mg |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | emtricitabine | 23,950 ng/mg |
| Period 2: TDF-FTC (Dual IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | tenofovir diphosphate | 289 ng/mg |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | maraviroc | 141.8 ng/mg |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | tenofovir diphosphate | 301.9 ng/mg |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | emtricitabine | 104 ng/mg |
| Period 3: TDF-FTC-MVC (Triple IVR) | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | tenofovir | 5.1 ng/mg |
Secondary
Acceptability of the IVRs
Acceptability of the IVRs was assessed through reported willingness to use the IVR for 28 days in a real-world setting on a likert scale, 1 being not at all confident to 5 being completely confident for Periods 1 and 2.
Time frame: Days 0-21 following insertion of each IVR.
Population: Data was not collected for the third study period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Period 1: TDF (Single IVR) | Acceptability of the IVRs | 3.5 units on a scale |
| Period 2: TDF-FTC (Dual IVR) | Acceptability of the IVRs | 4 units on a scale |