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
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
10
University of Texas Medical Branch
Galveston, Texas, United States
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.
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).
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).
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).
Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma
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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).
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.
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.