Tenofovir and HIV Prevention Studies
A10-113 - Phase 1
Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Tenofovir 1% Gel Using the BAT 24 Regimen Versus Daily and Pericoital Dosing
This Phase I multi-site study examined the pharmacokinetics (PK), pharmacodynamics (PD) and immune system effect of the BAT24 dosing regimen versus daily and pericoital dosing regimens with vaginal use of tenofovir 1% gel after a single sex act and after multiple sex acts. The study enrolled healthy, monogamous women at low risk for STIs and for pregnancy.
TFV concentrations were assessed in blood plasma, aspirate, and tissue; TFV-DP in PBMCs, endocervical cells, and tissue. In addition, the PD effect of TFV was assessed using an HIV-1 explant challenge model; anti-HIV and anti-HSV activity in CVL; and immune cell activation (and possibly mucosal histology) .
TFV gel dosing regimens, were assigned as follows:
BAT24: 1 hour before and 1 hour after sex
Precoital: 1 hour before sex
Postcoital: 1 hour after sex
Daily: Each day or evening at about the same time with the last study-sex 12 hours after the final dose
Clinicaltrials.gov Identifier: NCT01369303
Status: Study completed, Abstract OA13.03. HIV R4P 2014, Cape Town, South Africa
A10-114 – Phase 1
Assessing the Effect of Contraception and the Menstrual Cycle on Pharmacokinetics, Pharmacodynamics, and Vaginal Safety in Tenofovir Vaginal Gel Users
This Phase I, prospective, open-label, parallel cohort study examined the effects of two contraceptive methods (oral contraceptives [OCs] and DMPA) and the menstrual cycle on the pharmacokinetics (PK), pharmacodynamics (PD), and safety of tenofovir (TFV) 1% gel, and the effect of the contraceptive methods on markers of mucosal immunity among healthy women. The study enrolled healthy women aged 18-50 with regular menstrual cycles and at low risk for sexually transmiatted infections.61 participants completed the across three sites.
Each participant was seen in 6 visits. Following consent and confirmation of eligibility, participants underwent baseline sampling. Women were asked to use 2 gel applicators inserted 2 hours apart in a modified BAT24 regimen and randomized to return either 3 or 11 hours after insertion of the second gel. Blood and genital samples were collected during different phases of the menstrual cycle, before and after starting their chosen contraceptive method, and with and without product use.
Clinicaltrials.gov Identifier: NCT01421368
Status: Study completed, manuscript is in progress.
A11-118 – Phase 1
In Vivo Drug Interaction Pharmacokinetic Study of Tenofovir 1% Gel and Three Commonly Used Vaginal Products
This Phase I, randomized multi-site study aimed to determine if concomitant administration of Tenofovir (TFV) 1% vaginal microbicide gel and a non-microbicide vaginal product (antifungal cream, antimicrobial gel, or the combination contraceptive intravaginal ring [IVR]) changes local and/or systemic exposure compared to TFV alone or vaginal product alone. As there were no comparisons between vaginal product groups, the study consisted of three separate crossover studies. The study enrolled healthy women at low risk for sexually transmitted infections (STIs) and pregnancy, aged 18-50 with regular menstrual cycles. 46 participants completed the study (18 antifungal cream, 13 antimicrobial gel, 15 IVR).
Participants had up to 8 visits. Following consent and confirmation of eligibility at Visit 1, participants underwent 3 crossover treatment periods in a randomized order: vaginal product alone, TFV gel alone; and both products in combination. Within each crossover treatment period there were 2 visits, with the sampling visit (collection of plasma and genital tissue) occurring after product use was complete.
Product usage and during the 3 treatment conditions was as follows:
- Treatment Condition (vaginal product alone): The participant was instructed to use her assigned product for 5 to 21 days, depending on the dosing instructions for the particular product.
- Treatment Condition (TFV gel alone): The participant was instructed to use TFV gel for 7 days, inserted twice a day with each dose approximately 12 hours apart.
- Treatment Condition (vaginal product and TFV gel): The participant was instructed to use her assigned product for 5 to 21 days, depending on the dosing instructions for the particular product. TFV gel was used for 7 days, inserted twice a day with each dose approximately 12 hours apart; the morning insertion of TFV gel occurred approximately two hours after insertion of the vaginal product (for the gel and cream cohorts).
Clinicaltrials.gov Identifier: NCT01813162
Status: Study completed, manuscript is in process.
A12-124 – Phase 1
Influence of Female Reproductive Cycle and Menopause on Cervicovaginal Tissue Susceptibility to HIV-1 Infection and Tenofovir 1% Gel Activity
This Phase I open label study assessed tenofovir pharmacokinetic and pharmacodynamic endpoints, cervicovaginal safety parameters, explant susceptibility to HIV infection and objective measures of vaginal applicator use in premenopausal women (in the follicular and luteal phase of the menstrual cycle) and postmenopausal women (before and after treatment with estradiol vaginal cream). The study, conducted at a single site, completed 20 premenopausal women and 17 postmenopausal women.
Premenopausal women were seen in 5 study visits and postmenopausal women were seen in 6 study visits. All participants were contacted by one scheduled follow-up telephone call after their final study visit.
Premenopausal women: Following consent and confirmation of eligibility at Visit 1, baseline blood and genital samples were taken in the follicular and luteal phase (Visits 2 and 3) of her menstrual cycle. The participant was then given TFV gel and instructed to insert two doses, separated by 2 hours, and return to the clinic 3 hours (± 1 hour) after the second gel insertion for post gel samples. The post gel samples will be taken in the follicular and luteal phase (Visits 4 and 5).
Postmenopausal women: Following consent and confirmation of eligibility at Visit 1, baseline blood and genital samples were taken (Visit 2). The participant was then given TFV gel and instructed to insert two doses, separated by 2 hours, and return to the clinic 3 hours (± 1 hour) after the second gel insertion for post TFV gel blood and genital samples (Visit 3). Vaginal estradiol cream was distributed at Visit 4; participants will be instructed to insert two grams of estradiol cream in to the vagina every night for 14 days, and then one gram of estradiol cream into the vagina every other night until approximately 48 hours prior to Visit 5. Post estradiol blood and genital samples will be taken at Visit 5. The participant was then given TFV gel and inserted two doses as before, while continuing use of estradiol cream. Post TFV gel blood and genital samples will be were taken Visit 6.
For postmenopausal women, blood and genital samples were collected at baseline, as well as before and after gel use (with and without use of estradiol cream).
Clinicaltrials.gov Identifier: NCT01810315
Status: Study completed, manuscript accepted. Abstract accepted to 2016 HIVR4P, oral presentation scheduled in session, It Takes Two to Tango: Host, Hormones and Drug Levels in the Mucosa on 18 October 2016. The session will be held from 10:30 - 12:00.
A15-137 – Phase I
Exploratory Pharmacokinetic and Pharmacodynamic Study of Oral F/TAF for the Prevention of HIV Acquisition
This phase I, prospective, randomized PK/PD study will focus on the pharmacokinetics and pharmacodynamics of F/TAF oral tablets to assess systemic and genital tract bioavailability in healthy women. It will also evaluate the feasibility of event-driven use.
Based on the properties of TAF, the data supports that a lower dose of TAF (10 or 25 mg) compared with the current dose of TDF in F/TDF (300 mg) will result in lower systemic exposure to drug and higher intracellular levels of the active metabolite, thus maintaining or improving antiviral efficacy while improving the safety profile, and reducing the cost and size of the tablets. Given this improved safety and efficacy profile, that F/TDF is approved for HIV prevention as a daily method, and that an F/TAF-containing regimen is already approved for a treatment indication, F/TAF is a good candidate for oral HIV pre-exposure prophylaxis (PrEP) and could provide an effective prevention option with a more favorable safety profile than F/TDF. In addition, the lower dose of TAF reduces costs and size, making the new combination an appealing PrEP candidate for women in low-resource countries.
The study will complete approximately 72 healthy, non-pregnant, HIV negative, premenopausal women (aged 18-50) across three sites who are not at risk of pregnancy and are at low risk for sexually transmitted infections (STIs).
Status: Recruitment to begin September 2016
A15-140 - Phase I
Exploratory Pharmacodynamic Study of Tenofovir-Based Products
This Phase I, prospective, parallel study was designed to compare the anti-HIV efficacy of emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) (Truvada®) tablet and tenofovir (TFV) intravaginal rings (IVR) at the cervico-vaginal mucosal and fluid level using ex-vivo HIV infection models. The study enrolled healthy, non-pregnant, HIV negative, premenopausal women (aged 18-50, with regular menstrual cycles), who are not at risk of pregnancy. Participants were assigned to the use of F/TDF oral tablet or TFV IVR.
During this study, participants completed 4 visits over a period of two to three months. At Visit 1 volunteers will be consented and undergo procedures to confirm they are eligible to continue in the study. Baseline blood for HIV, complete blood count (CBC), serum chemistries (including creatinine to calculate CrCl) and Hepatitis B surface antigen (HBsAg) will be collected. Genital swabs will also be collected to test for Trichomonas, Gonorrhea and Chlamydia.
At Visit 2 eligibility to participate in the study was confirmed. CVF and biopsies were collected. The participants were instructed on the proper care of the biopsy sites to optimize healing. At Visit 3 a pelvic exam was conducted to ensure the site of biopsies has healed. Participant were given the study product assigned and instructed as to appropriate use per the study requirements. Each product was used for 14 days after which the participant returned to the clinic for Visit 4. Participant were contacted each day to confirm adherence. At Visit 4, questions were asked about product use per the study protocol. Follow-up blood, CVF and CV biopsies were collected, and participants were reminded of proper care of biopsy sites. Final follow-up telephone calls were conducted approximately 1 to 2 weeks after Visit 4 to ask about adverse events (AEs) experienced since the last visit. Participant were then exited unless any symptoms required follow up.
ClinicalTrials.gov Identifier: NCT02722343
Status: Completed, in analysis
Vaginal Insert Studies
A11-117 - Phase I
Assessing the Safety, Pharmacokinetics, Pharmacodynamics, and Disintegration Time of Vaginal Inserts Containing Tenofovir and/or Emtricitabine
This Phase I, randomized, placebo-controlled, multi-site study examined the genital and systemic safety, pharmacokinetics (PK), pharmacodynamics (PD), disintegration and disappearance times, and acceptability of four vaginal tablets: 1) Tenofovir (TFV) alone; 2) Emtricitabine (FTC) alone; 3) TFV combined with FTC; and 4) placebo. Participants were randomized to treatment group, to number of tablets to be inserted in the Single Use Phase, and to one of four collection time points (2, 4, 6, or 24 hours after tablet insertion) for assessments after the last dose of the Multiple Use Phase. The study enrolled healthy, HIV-uninfected women aged 18-50 with menstrual cycles of 25-35 days and either sexually abstinent or in a monogamous relationship with a healthy partner. 47 participants completed the study across two sites.
Each participant had at least 6 study visits and 2 follow-up safety phone calls. Following consent and confirmation of eligibility at Visit 1, baseline sampling occurred at Visit 2 and randomization at Visit 3, along with the Single Use Phase. In the Single Use Phase of the study, participants inserted one tablet in the clinic to estimate times to disintegration and disappearance. Those randomized to two tablets inserted a second tablet 2 hours later. In all women, sample collection for PK and PD assessments occurred 5 hours after the initial tablet insertion.
In the Multiple Use Phase of the study, participants inserted a tablet once daily for 14 days. The 1st, 7th, and 14th tablets were inserted in the clinic; the remaining tablets were inserted at home. Each insertion in the clinic was followed at the participant’s assigned time point by sample collection for PK and PD assessments.
Clinicaltrials.gov Identifier: NCT01694407
Status: Study completed, manuscript in progress. Presented at IAS 2015.
D15-134 - Assessing the Disintegration, Safety, and Acceptability of Placebo Vaginal Inserts for the Delivery of Vaginal Products
This open-label, single-site study examined the disintegration/disappearance time, safety, and acceptability of placebo vaginal inserts. Participants will use a placebo vaginal insert twice: first for an in-clinic disintegration/safety assessment, and a second time for an at-home acceptability assessment, with safety assessed at the following clinic visit. Participants will include women 18-50 years old who are not at risk of pregnancy due to abstinence, sterilization, condom use, or same-sex relationship.
Once eligibility has been confirmed, the participant will complete an in-clinic disintegration test to estimate the amount of time required for disintegration and complete disappearance of the vaginal insert. Following the disintegration test, vaginal swab(s) will be collected for development of adherence measures. 24 to 72 hours following the in-clinic disintegration test, the participant will use the vaginal insert at home and complete a standardized acceptability questionnaire 4 hours and 24 hours after placement. The final clinic visit will be scheduled 24-72 hours after placement of the vaginal insert used at home, and will include a pelvic exam to assess safety and vaginal swab(s) will be collected for development of adherence measures. The participant will exit the study following the final study visit.
This study is designed to test a single placebo vaginal insert. Participants may re-enroll in the study as additional inserts become available for testing.
Clinicaltrials.gov Identifier: NCT02534779
Status: Study completed, manuscript in progress.
A13-128 - Phase I One-Month Safety, Pharmacokinetic, Pharmacodynamic, and Acceptability Study of Intravaginal Rings Releasing Tenofovir and Levonorgestrel or Tenofovir Alone
This Phase I, randomized, placebo-controlled, multi-site study aims to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and acceptability of the tenofovir and levonorgestrel intravaginal ring (TFV/LNG IVR) and the TFV-only IVR. Participants were randomized to type of IVR in a 2:2:1 ratio (TFV/LNG:TFV-only:placebo), as well as sampling time points. The study enrolled healthy, non-pregnant, ovulatory, HIV-uninfected women aged 18 to 45 with a body mass index (BMI) less than 30 kg/m2. 50 participants completed the study across two sites.
Each participant had up to 9 study visits, depending on randomization. Following consent at Visit 1 and confirmation of eligibility, including confirmation of ovulation, at Visits 1 and 2, participants underwent baseline sampling at Visit 3. Randomization and initiation of IVR occurred at Visit 4. Participants were randomized to type of IVR in a 2:2:1 ratio (TFV/LNG:TFV-only:placebo), as well as sampling time point at Visit 4 (1, 2, 4, or 8 hour post IVR insertion) and TFV PK biopsy collection time point post IVR removal (24 or 72 hours).
Sample collection occurred 24 hours post IVR insertion (Visit 5), on the day of ovulation (Visit 6), based on an ovulation predictor kit, 8-10 days following ovulation (Visit 7), 24 hours post IVR removal (Visit 8), and, based on randomization, 72 hours post IVR removal (Visit 9). Colposcopy was performed at Visit 4 (pre IVR insertion), 5, 6, and 7. In addition to samples, an acceptability questionnaire was completed at Visit 7, pre IVR removal. All participants received a follow up safety phone call 1-2 weeks following their last study visit.
Clinicaltrials.gov Identifier: NCT02235662
Status: Study completed, analysis ongoing.
A13-126 - A Phase I Postcoital Testing Study of the SILCS Diaphragm Used with 3% Nonoxynol-9 Gel, ContraGel®, or no Gel
This is a Phase I multi-center, randomized, crossover, non-significant risk device study to assess the ability of the SILCS diaphragm (now marketed as Caya) used with ContraGel to prevent sperm from penetrating midcycle cervical mucus. By carrying out three test cycles, one using the device with ContraGel, one using the device with spermicide (3% nonoxynol-9 [N-9]), and one using the device with no gel, the function of the mechanical barrier alone and the contribution of the addition of the ContraGel or spermicide in preventing sperm from penetrating midcycle cervical mucus will be assessed. The sequence of product use will be determined by randomization. The study will enroll healthy, sexually active women with regular menstrual cycles who have undergone female tubal sterilization.
Each participant will be seen in approximately 9 visits, over a period of 6-8 months. Following consent and confirmation of eligibility at Visit 1, each participant will undergo four postcoital test (PCT) cycles. The first PCT cycle will be done without the use of any product, in order to demonstrate the participant’s ability to undergo normal ovulatory events and to produce receptive, midcycle cervical mucus. The partner’s ability to produce motile sperm capable of penetrating the cervical mucus is also evaluated in this cycle. Test PCT cycles will be carried out during the subsequent menstrual cycles using either the SILCS diaphragm with 3% N-9, the SILCS diaphragm with ContraGel, or the SILCS diaphragm alone following a sequence of randomized treatment.
Clinicaltrials.gov Identifier: NCT02309554
Status: Study completed, manuscript in progress
A13-127 - A Phase I Safety study of the Caya diaphragm used with ContraGel
This Phase I randomized, single site, parallel, study will compare the safety of ContraGel delivered by the Caya diaphragm versus HEC universal placebo gel delivered by the Caya diaphragm. The study will enroll approximately 24 healthy women, aged 18-50 years of age, protected from pregnancy by sterilization.
Women will use the assigned product during two 7-day periods of daily use, the first without intercourse and the second with intercourse. An assessment of safety includes adverse events, epithelial integrity and anti-bacterial activity. Samples collected during the study include cervical tissues, and cervicovaginal fluid taken at baseline and pre-and-post each 7-day period of product use.
Clinicaltrials.gov Identifier: NCT02462954
Status: Study completed, analysis ongoing.
D09-108 - A Randomized Cross-Over Study of Vaginal Semen Exposure and Clinical Failure Comparing the PATH Woman’s Condom and the FC2 Female Condom
This is a comparative, open-label two-period crossover study comparing the PATH Woman’s Condom to the FC2 female condom to provide data on functional performance, vaginal semen exposure, safety, and acceptability of the two female condoms. 490 healthy, heterosexual couples at least 18 years of age and at low risk for pregnancy or STIs completed the study.
Status: Completed, in analysis
Limiting male contraception to vasectomies and condoms, as is the case today, is very restrictive. CONRAD supported investigators aggressively researching different compounds that disrupt sperm production and function, so that safe, effective and inexpensive contraceptives can be offered to men. In collaboration with the World Health Organization (WHO), CONRAD conducted a clinical trial of a long-acting injectable hormonal contraceptive for men in several countries.
A25165 – Single arm Phase IIb
Sperm Suppression and Contraceptive Protections Provided by Norethisterone Enantate (NET-EN) Combined with Testosterone Undecanoate (TU) in Healthy Men
This study evaluated whether the combination of a progestin, norethisterone enantate (NET-EN), and an androgen, testosterone undecanoate (TU), delivered via injection, represents a safe and effective method of male fertility regulation. Participants were healthy male subjects ages 18-45 years, involved in a stable relationship (according to their judgment and to the investigator’s judgment) with an 18-39 year-old female partner. Ten sites in 7 countries began enrolling trial participants in 2008; enrollment ended in September 2010. Participants received injections every 2 months during the Suppression and Efficacy Phases. While interim data showed that the method suppressed sperm production effectively, further injections were discontinued in April 2011 after a WHO review panel determined that the risks of possible side effects might outweigh the potential benefits to male participants. The side effects experienced by participants were not unexpected, but occurred more often than anticipated.
Protocol/serial number: WHO/HRP ID A25165
Status: Manuscript pending
Female Reproductive Health Studies
A14-131 - The Role of Vitamin D in Female Reproductive Tract Immunity
This single site, outpatient, open label study assessed the impact of 8 weeks of Vitamin D and calcium supplementation, using daily versus weekly supplementation regimens, on female reproductive tract immunity. The study enrolled healthy, non-pregnant, HIV-uninfected premenopausal women, defined as aged 21 – 50. 20 participants completed the study.
Women received a dose of Vitamin D 4000 IU daily or 50,000 IU weekly, in capsule form, for 8 weeks along with 1000 mg of calcium daily. Blood and genital samples were taken at baseline and after taking Vitamin D. Concentrations of Vitamin D in serum were measured along with, measures of cervicovaginal innate immune function, including antimicrobial and proinflammatory gene expression, Toll-like receptor (TLR)-mediated responses, immunohistochemical (IHC) analysis of immune cell markers, susceptibility to HIV infection, and vaginal microbiota.
Clinicaltrials.gov Identifier: NCT02186535
Status: Completed, results pending
Biomarker and Adherence Studies
D11-119 – Phase 1
Identification of novel biomarkers of cervicovaginal mucosal inflammation
This Phase I outpatient, open label study investigated the response of vaginal and cervical tissue after exposure to three vaginal products: hydroxyethyl cellulose (HEC) placebo, nonoxynol-9 (N9) and imiquimod (IMQ) cream. The study completed 17 healthy, ovulatory women, aged 21 to 45, at one US site who were not using hormonal contraception and were not at risk of pregnancy.
Genital samples were collected in the follicular and luteal phases of a control menstrual cycle. Participants were then randomized to the order of using the 3 vaginal products, used each product for 2-3 days within days 15 – 23 of the next three menstrual cycles, and provided genital samples in the luteal phase of each cycle. Post vaginal compound use sampling took place approximately 8 – 18 hours after the last vaginal dose of all three products.
Clinicaltrials.gov Identifier: NCT01593124
Status: Study completed
D11-115 –Phase 1
Prospective Evaluation of the Impact of Bacterial Vaginosis and its Treatment on Mucosal Susceptibility to HIV-1 Infection and Endpoints of CervicoVaginal Safety
This Phase I, open-label study investigated whether BV affects the cervicovaginal tissue and makes women at higher risk for HIV acquisition. At one US site, the study completed 33 women, age 18-50, with a current bacterial vaginosis (BV) infection or intermediate vaginal flora.
Over three scheduled visits and approximately two months, vaginal and cervical tissue was collected and infected with HIV ex vivo. The study evaluated HIV infection and safety at 3 different time periods (during BV infection; approximately 1 week after completing a 7-day course of metronidazole therapy; and approximately 1 month after completing the 7-day course of metronidazole therapy).
Clinicaltrials.gov Identifier: NCT01347632
Status: Study completed, manuscript published.:Thurman AR, Kimble TD, Herold BH, Mesquita PMM, Fichorova RN, Dawood HY, Fashemi T, Chandra N, Rabe L, Cunningham TD, Anderson SM, Schwartz JL, Doncel GF. Bacterial vaginaosis and sub-clinical markers of genital tract inflammation and mucosal immunity. AIDS Res Human Retrovir 2015;31(11):1139-52.
D13-125 - Comparison of Objective Biomarkers of Protocol Compliance and Product Adherence with Classic Markers of Compliance and Adherence
This single site cross sectional study of healthy women aged 18 to 50 years old was designed to determine the sensitivity, specificity, positive predictive value, and negative predictive value of tests of vaginal insertion of product applicators for markers of adherence. Analysis of returned applicators included: visual inspection of returned applicators (VIRA), UV light inspection, DNA sequences of vaginal bacteria and immunohistochemical tests for protein markers.
Each enrolled participant had one enrollment/sampling visit with a follow-up safety telephone call approximately 7 to 14 days later. Each participant provided a total of 12 applicators:
- Four handled by the participant, but not inserted into the vagina and the gel expelled into a waste container
- Four applicators inserted into the participant’s vagina, one at a time, by the investigator, removed, and then the gel expelled into a waste container
- Two applicators inserted into the participant’s vagina, one at a time, and gel expelled into the participant’s vagina; and
- Two applicators inserted into the vagina, one at a time, by the investigator, removed and then the gel expelled into a waste container.
Clinicaltrials.gov Identifier: NCT01804023
Status: Study complete. Manuscript published: Thurman AR, Jacot TA, Kimble TD, Mauck CM, Nelson A, Schwartz JL, Doncel GF. Comparison of Visual and Ultraviolet Light Inspection versus DNA/Protein Biomarkers to Assess Product Adherence with Vaginal Microbicide Applicators. Sex Trans Dis, 2014;41(12):739-46.
D15-135 – Phase 1
Development of Adherence Biomarkers for Multiple Microbicide and Multipurpose Prevention Technology (MPT) Dosage Forms
The purpose of this Phase I, open label study is to develop markers for use of placebo vaginal products and measure markers of mucosal semen exposure and monitor safety of placebo product use. At one US site, the study aims to enroll healthy women, age 18-50, who are protected from pregnancy. Four types of placebo products will be available for assigned use, and women may choose to use up to all four products, serially:
- Intravaginal ring (IVR) - approximately 20 participants to complete
- HEC universal placebo gel - approximately 10 participants to complete
- Vaginal film - approximately 10 participants to complete
- Vaginal insert – approximately 10 participants to complete
Participants assigned to vaginal insert, film or gel will provide pre-product use vaginal swabs, and then will use the assigned product with and without timed intercourse with their male partner for a total of two doses of the product. Vaginal swabs will be collected post product use at the clinic and, self-collected at-home swabs will be returned to the clinic after each of two weeks. Participants will be seen over 4 visits.
Participants using the IVR do not have to be sexually active with a male partner, and will be seen over 5 visits and use a total of 3 IVRs; IVR1 will be used for approximately 24 – 36 hours, IVR2 for approximately 7 – 10 days and IVR3 for approximately 28 – 32 days. Swabs will be collected pre-product use and before each IVR is inserted.
Clinicaltrials.gov Identifier: NCT02569697
Status: Study completed, analysis ongoing
Human-Centered Design Studies
Human-Centered Design (HCD) is a research-driven, design-focused approach to creating solutions that require change in human behavior or actions. For example, what type of messaging, packaging and product attributes should an HIV prevention product have that would be most attractive to young African women – and motivate them to use it consistently?
While there is existing literature from socio-behavioral studies discussing how lifestyles, hygiene practices, sexual risk taking, activities preceding intercourse, and potential for covert use may affect the uptake of microbicides, these studies remain distinct from the HCD research. HCD studies focus not only on individual behavior and social, peer and community influences, but extend to understanding how product design, branding, packaging and messaging influence the user’s choices, confidence and long term engagement with the product. Given the complicated factors that surround uptake of a product designed to prevent HIV, HCD may provide valuable and additional insights into end-user preferences.
Thanks to the funding and support of PEPFAR through USAID, CONRAD is collaborating with the global design firm IDEO and other partners to find HCD solutions to improve adherence to microbicides, and ultimately, to implement these solutions in a way that will make a real impact in preventing new HIV infections.
In 2014, CONRAD partnered with IDEO to bring an integrated and iterative research strategy to the microbicide field. IDEO utilized the CAPRISA team as an in-country partner, which focused on drug delivery systems (DDSs) (microbicide gels, IVRs, tablets and films), product messaging, and access/adherence strategies (digital and analogue reminders, websites, mobile applications). These initial pilot data identified several key drivers and potential barriers to microbicide uptake, correct use and long term adherence, which needs further qualitative and quantitative testing among high risk end users from an expanded geographic, socioeconomic and cultural scope.
During Project KAROO, IDEO interacted with a cross-section of individuals in South Africa, including potential end users from the general population, traditional healers, physicians, clinic personnel, designers, community leaders and influencers. In response to insights gained from the initial discussions, the team designed three distinct communication themed prototypes, focusing on intimacy, hygiene and female empowerment. By the end of the project, IDEO developed potential story boards and prototypes for billboards, advertisements and interest building events as well as innovative and aspirational deliverables such as a refined starter package, home-based refill storage package and travel/carrying clutches for the various DDSs. Messaging campaigns and proposals for innovative demand generation and engagement activities were also proposed. This project represented an innovative approach to investigating the complex factors involved in microbicide implementation.
CONRAD is working with IDEO, South African partners Instant Grass and Matchboxology and collaborators CAPRISA, RTI International and Abt Associates to interview women, their partners and community members to better understand drivers for and barriers to product use. This research informs design, packaging, access and messaging in order to increase demand, use and adherence. Participants involve women who are at the highest risk of HIV infection, especially young unmarried women, including young adults who still live with their parents, those with a current or past history of intimate partner violence and those who exchange sex for money. Project EMOTION will develop new product attributes, packaging, dispensing systems, messaging, dosing preferences, and branding for two lead HIV prevention products, as well as at least two new alternative drug delivery systems. A communication campaign for one leading dosage form will also be designed and prototyped.
Status: Completed first HCD trip (Kalahari 1), interviewing over 50 young women, men, health care providers and community leaders in both urban and rural regions in South Africa. Eight PrEP products (oral tablet, vaginal ring, injectable, patch, vaginal insert, vaginal film, intrauterine device, implant) were examined by interview participants who shared their opinions on each product. Unique umbrella brand was developed; message themes were outlined. Two products were selected for Kalahari 2 which was completed in the summer of 2016. Findings from Kalahari 2 will be shared in a poster and a satellite session at the HIVR4P conference in Chicago. The satellite, entitled “Sex, Intimacy and HIV Prevention: What do women and their partners really want? Incorporating end-user input and developing a market launch strategy for PrEP” will be on Friday, October 21st from 9am to noon.
The Quatro Study - Acceptability Study of (Placebo) Vaginal Delivery Forms for Preventing HIV and Unintended Pregnancy
The purpose of The Quatro Study is to assess the acceptability, preferences, user experience and effect on sexual behavior of four different vaginal microbicide or multi-purpose technology (MPT) delivery forms, using placebo products in 18-30 year old African women: rapidly disintegrating vaginal insert, intravaginal ring (IVR), film and gel. The study also will examine adherence to the dosage forms through objective markers, developed for each dosage form prior to the commencement of the clinical acceptability study. The study will be conducted at sites in two sub-Saharan African communities.
The Quatro Study includes the following components:
- A formative research phase, pretesting rating and preference (attitudinal) output measures via in-depth interviews at each site.
- A clinical acceptability study, (n=200) to determine ratings and relative preference rankings of the four vaginal delivery forms of placebo microbicide/MPT among young women (aged 18 to 30) evaluated through stated preference, choice, and use.
- A Discrete-Choice Experiment/Conjoint Analysis, where product-experienced (from the clinical acceptability study) and product-naïve (N=200, newly recruited) women will choose and give feedback on product attributes and related factors influencing use.
- Focus group discussions, made up of a random subset of product-experienced participants, to investigate preferences for varied product attributes of each dosage form.
- Key informant interviews, to evaluate health care provider and other key stakeholders’ attitudes toward the different product and to explore perceptions of appropriate educational and marketing messages for each delivery form.
Clinicaltrials.gov Identifier: NCT02602366
Status: Recruiting for formative research phase.