PrEP Pod-IVR for HIV Prevention

(PrEP-Pod-IVR Trial)

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Oak Crest Institute of Science

Must not be taking: Anticoagulants, NSAIDs, Immunomodulators, others

Disqualifiers: Pregnancy, HIV, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

15 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications. The trial requires participants to abstain from using specific medications, such as blood thinners like Warfarin and certain NSAIDs (like ibuprofen) before biopsies, as well as rectally or vaginally administered medications during the study.

What data supports the effectiveness of the drug Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC) for HIV prevention?

Research shows that Tenofovir Disoproxil Fumarate (TDF) combined with Emtricitabine (FTC) is effective in preventing HIV, reducing the risk of infection by 74 to 92% when used as pre-exposure prophylaxis (PrEP). This combination has been successful in various populations, including men who have sex with men and serodiscordant couples (where one partner is HIV-positive and the other is not). ^{1 2 3 4 5}

Is the PrEP Pod-IVR treatment safe for humans?

The combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has been used safely for HIV prevention, but some people have experienced side effects like nausea, changes in kidney function, and reduced bone strength. ^{1 3 6 7 8}

How is the PrEP Pod-IVR drug for HIV prevention different from other treatments?

The PrEP Pod-IVR drug uses Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine (FTC), which are effective in reducing the risk of HIV infection by up to 92% when drug levels are detectable. This combination is unique because it is specifically approved for pre-exposure prophylaxis (PrEP) to prevent HIV, offering a proactive approach to HIV prevention. ^{1 3 8 9 10}

What is the purpose of this trial?

Participants will have a 28-day pre-ring baseline assessment period (Stage 1) followed by randomization to order with 5 participants per study arm. All participants will sequentially receive both study products for 28-days with at least a 2-week washout period between products. Arm 1 will receive the TDF-FTC pod-IVR for Stage 2 followed by the placebo pod-IVR during Stage 3. Arm 2 will receive the placebo pod-IVR for Stage 2 followed by the TDF-FTC pod-IVR during Stage 3. During Stages 2 \& 3 participants will also complete brief phone surveys (\<3 min), computer-assisted self-interviews (CASIs), and in-depth interviews (IDIs) regarding perceptibility and acceptability. If willing, participants' male sexual partners will be invited to complete IDIs as well.

Research Team

Kathleen L Vincent, MD

Principal Investigator

University of Texas

Eligibility Criteria

This trial is for HIV-negative women aged 18-45 in good health, with regular menstrual cycles or controlled by certain contraceptives. They must not be pregnant, breastfeeding, or planning pregnancy and should agree to avoid vaginal products and intercourse as specified. Male partners can participate if they consent to interviews and use provided condoms.

Inclusion Criteria

My male partner meets the study's specific health criteria.

Abstain from use of any vaginal products other than study products for the duration of the study

Abstain from receptive oral, vaginal, or anal intercourse during specific periods

Exclusion Criteria

I haven't used any specified medications or products in the last 4 weeks.

Participating in another research study involving drugs or medical devices within the specified time frames

I have not had any gynecologic or genital procedures in the last 60 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo a 28-day pre-ring baseline assessment period

4 weeks

1 visit (in-person)

Treatment Stage 2

Participants receive either TDF-FTC pod-IVR or placebo pod-IVR for 28 days

4 weeks

Multiple visits (in-person and virtual)

Washout Period

A 2-week washout period between treatments

2 weeks

Treatment Stage 3

Participants receive the alternate pod-IVR (TDF-FTC or placebo) for 28 days

4 weeks

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC)

Trial Overview The study tests a TDF-FTC pod-IVR (a vaginal ring for HIV prevention) against a placebo over two stages, each lasting 28 days with a washout period in between. Participants will also provide feedback through surveys and interviews about the product's feel and acceptability.

Participant Groups

Group I: Arm 2 Experimental Treatment 2 Interventions

Arm 2 will receive the placebo pod-IVR for Stage 2 followed by the Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC) pod-IVR during Stage 3.

Group II: Arm 1 Experimental Treatment 2 Interventions

Arm 1 will receive the Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC) pod-IVR for Stage 2 followed by the placebo pod-IVR during Stage 3.

Who Is Running the Clinical Trial?

Oak Crest Institute of Science

Lead Sponsor

Trials

3

Recruited

120+

The Miriam Hospital

Collaborator

Trials

252

Recruited

39,200+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Vanderbilt University

Collaborator

Trials

714

Recruited

6,143,000+

The University of Texas Medical Branch, Galveston

Collaborator

Trials

263

Recruited

55,400+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Findings from Research

Tenofovir disoproxil fumarate coformulated with emtricitabine (TDF/FTC) is a safe and highly effective medication for preventing HIV transmission, yet only about 200,000 Americans have started using it for pre-exposure prophylaxis (PrEP), leaving 80%-90% of those at highest risk without access.

Barriers to PrEP uptake include costs, anticipated side effects, and stigma, but innovative strategies like engaging nonmedical staff and developing new technologies are being explored to improve adherence and make PrEP more accessible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PrEP 1.0 and Beyond: Optimizing a Biobehavioral Intervention. Mayer, KH., Allan-Blitz, LT.[2020]

Topical tenofovir gel and daily oral tenofovir/emtricitabine (FTC/TDF) have shown significant efficacy in preventing HIV-1, with reductions in acquisition rates of 39% and 44% respectively in various studies involving different populations.

While tenofovir gel was effective in African women and oral FTC/TDF showed efficacy in men who have sex with men (MSM) and serodiscordant couples, some studies in African women found no efficacy, prompting further investigation into the reasons behind these differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir-based pre-exposure prophylaxis for HIV prevention: evolving evidence. Celum, C., Baeten, JM.[2021]

Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are effective in reducing the risk of HIV infection by 74 to 92% when taken as pre-exposure prophylaxis (PrEP) with detectable drug levels.

While TDF-FTC can cause side effects like nausea and decreased bone mineral density, these risks can be managed through regular monitoring by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug safety evaluation of oral tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis for human immunodeficiency virus infection. Trang, TP., Dong, BJ., Kojima, N., et al.[2017]

Tenofovir disoproxil fumarate (TDF) and its combination with emtricitabine (FTC), marketed as Truvada®, have been shown to be effective in preventing HIV infection when taken orally, either daily or intermittently, in various populations including men who have sex with men and serodiscordant couples.

Topical tenofovir gel has also demonstrated effectiveness in preventing HIV infection in women, highlighting the versatility of tenofovir-based interventions in HIV prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-exposure chemoprophylaxis of HIV infection: quo vadis? Clercq, ED.[2015]

Oral tenofovir disoproxil and emtricitabine (FTC) for HIV preexposure prophylaxis (PrEP) is generally safe and well tolerated, with common gastrointestinal side effects that typically resolve within weeks.

While there is a slight decline in kidney function (eGFR) and bone mineral density (BMD) associated with the treatment, these changes are not clinically significant and tend to resolve after stopping the medication, making it a viable option for most adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of oral tenofovir disoproxil - emtricitabine for HIV preexposure prophylaxis in adults. Liegeon, G.[2022]

Using tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for preexposure prophylaxis (PrEP) is effective in preventing HIV-1 infections, with resistance to the drugs being rare if PrEP is started before infection occurs.

However, starting PrEP during an undiagnosed acute HIV-1 infection can lead to higher rates of drug resistance, particularly to tenofovir, highlighting the importance of screening for HIV before initiating PrEP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should we fear resistance from tenofovir/emtricitabine preexposure prophylaxis? Parikh, UM., Mellors, JW.[2018]

The study found that the combination of emtricitabine and tenofovir alafenamide (F/TAF) was safe and well-tolerated among HIV-uninfected women, with significantly lower gastrointestinal side effects compared to the older F/TDF combination.

F/TAF demonstrated higher concentrations of the active form of tenofovir (TFV-DP) in peripheral blood mononuclear cells and vaginal tissues compared to F/TDF, suggesting it may be a more effective option for HIV pre-exposure prophylaxis in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of a Tenofovir Alafenamide Fumarate-Emtricitabine based Oral Antiretroviral Regimen for Prevention of HIV Acquisition in Women: A Randomized Controlled Trial. Thurman, AR., Schwartz, JL., Cottrell, ML., et al.[2022]

Tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) has been approved for HIV pre-exposure prophylaxis (PrEP) since 2012, and while initial uptake was slow, recent surveys indicate growing acceptance among key populations.

Ongoing studies aim to improve PrEP implementation by identifying at-risk individuals in primary care settings and evaluating its use in HIV-discordant couples, highlighting the need for better education among healthcare providers and addressing financial barriers for underinsured patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiretroviral pre-exposure prophylaxis implementation in the United States: a work in progress. Mayer, KH., Hosek, S., Cohen, S., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

PrEP 1.0 and Beyond: Optimizing a Biobehavioral Intervention. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Tenofovir-based pre-exposure prophylaxis for HIV prevention: evolving evidence. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Drug safety evaluation of oral tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis for human immunodeficiency virus infection. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Pre-exposure chemoprophylaxis of HIV infection: quo vadis? [2015]

5. England pubmed.ncbi.nlm.nih.gov

Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of oral tenofovir disoproxil - emtricitabine for HIV preexposure prophylaxis in adults. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Should we fear resistance from tenofovir/emtricitabine preexposure prophylaxis? [2018]

8. England pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of a Tenofovir Alafenamide Fumarate-Emtricitabine based Oral Antiretroviral Regimen for Prevention of HIV Acquisition in Women: A Randomized Controlled Trial. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Antiretroviral pre-exposure prophylaxis implementation in the United States: a work in progress. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Suboptimal Uptake, Retention, and Adherence of Daily Oral Prexposure Prophylaxis Among People With Opioid Use Disorder Receiving Hepatitis C Virus Treatment. [2022]