Rectal vs Oral Tenofovir for HIV Prevention

Recruiting at 8 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: PrEP, Immunomodulators

Disqualifiers: HIV, Hepatitis B, Cardiac arrhythmia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which method better prevents HIV: a rectal douche (TFV rectal douche) or oral pills (Oral F/TDF Pills). Participants will try both treatments, switching after a short break, to assess preference and tolerance. Men who frequently engage in consensual receptive anal intercourse and regularly use enemas or rectal douches may be well-suited for this study. The focus is on safety and the practicality of these treatments in real-life settings. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain medications like F/TDF, F/TAF, or injectable PrEP within 8 weeks before the trial or during participation. If you are in the PK/PD sub-study, you must avoid using aspirin and NSAIDs around biopsy visits.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both treatments in this trial are safe for humans. The TFV rectal douche is safe and well-tolerated, with studies indicating that young men who have sex with men (YMSM) find it acceptable. Most people did not experience major side effects while using it.

The oral F/TDF pills are already approved for preventing HIV and have strong safety data. They are generally safe and well-tolerated when taken as directed, with past studies showing that most people do not experience significant side effects.

Both treatments have passed early safety tests in humans, suggesting they are likely well-tolerated. However, as with any medical treatment, reactions can vary. Participants should feel reassured by the existing data but also stay informed and communicate any concerns during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for HIV prevention because they explore different delivery methods for the active ingredient, tenofovir. Unlike traditional oral pills, one arm of the study employs a rectal douche, which could offer a more localized and potentially faster-acting preventive option. This approach not only targets the site of potential infection directly but may also provide an alternative for individuals who have difficulty with daily oral medication adherence. By evaluating both oral and rectal applications, scientists hope to broaden preventive strategies and tailor them to individual patient needs and preferences.

What evidence suggests that this trial's treatments could be effective for HIV prevention?

This trial will compare the TFV rectal douche and oral F/TDF pills for HIV prevention. Research shows both treatments hold promise. Studies have found that the TFV rectal douche delivers higher levels of the active drug to the tissue than oral TDF, potentially enhancing effectiveness in the colorectal area. It is also safe, easy to use, and generally acceptable to most people. Meanwhile, oral F/TDF pills have been proven to reduce the risk of HIV by up to 96% when taken regularly. Participants in this trial will receive both treatments in different sequences, providing strong options for preventing HIV. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals willing to compare two forms of a drug called Tenofovir: one taken by mouth and the other used as a rectal douche. Participants will try both methods in different sequences with a break in between. The study aims to assess safety, how well people like the method, if they stick with it, and how the body processes the drug.

Inclusion Criteria

Willing and able to provide informed consent to take part in the study

Able to read at a level required for the study components (e.g., CASI and SMS)

Have access to device and the internet for completion of study procedures

Exclusion Criteria

I currently have symptoms or a diagnosis of an infection in my rectal or reproductive area, or a urinary tract infection.

History of recurrent urticaria

I have used injectable PrEP before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Period 1 Treatment

Participants receive either rectal TFV douche or oral F/TDF for 8 weeks

8 weeks

Regular visits for safety and PK/PD assessments

Washout

A washout period between treatment sequences

2-4 weeks

Period 2 Treatment

Participants switch to the alternate treatment (oral F/TDF or rectal TFV douche) for 8 weeks

8 weeks

Regular visits for safety and PK/PD assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oral F/TDF Pills
• TFV rectal douche

Trial Overview The study is testing oral F/TDF pills against TFV rectal douches in an on-demand fashion over two periods. Each participant will use both formulations for 8 weeks each, separated by a short break. Researchers want to see which form is safer, more acceptable and effective based on adherence rates and drug levels in the body.

How Is the Trial Designed?

Group I: Group B Experimental Treatment 2 Interventions

Those participants assigned to Group B will start with the on-demand oral F/TDF 200 mg/300 mg sequence for 8 weeks and then after a 2-4 week washout will switch to the rectal TFV 660 mg douche for the next 8 weeks (Period 2).

Group II: Group A Experimental Treatment 2 Interventions

Those participants assigned to Group A will start with the rectal TFV 660 mg douche for the first 8 weeks (Period 1) and then after a 2-4 week washout will switch to the on-demand oral F/TDF 200 mg/300 mg sequence for the next 8 weeks (Period 2).

Oral F/TDF Pills is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Truvada for:

• HIV-1 Pre-Exposure Prophylaxis (PrEP)
• HIV-1 Infection Treatment

Approved in European Union as Truvada for:

• HIV-1 Pre-Exposure Prophylaxis (PrEP)
• HIV-1 Infection Treatment

Approved in Canada as Truvada for:

• HIV-1 Pre-Exposure Prophylaxis (PrEP)
• HIV-1 Infection Treatment

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a study involving 22 women, the tenofovir (TFV) intravaginal ring (IVR) showed significantly higher concentrations of TFV in cervicovaginal fluid and tissue compared to oral tenofovir disoproxil fumarate (TDF) combined with emtricitabine (FTC), indicating better localized antiviral activity.

The TFV IVR resulted in fewer adverse events and demonstrated greater HIV inhibitory activity in cervicovaginal fluid than the oral TDF/FTC regimen, suggesting it may be a safer and more effective option for mucosal protection against HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genital Mucosal Drug Concentrations and anti-HIV Activity in Tenofovir-Based PrEP Products: Intravaginal Ring vs. Oral Administration. Ouattara, LA., Thurman, AR., Jacot, TA., et al.[2023]

Tenofovir disoproxil fumarate (TDF) is an effective treatment for both HIV and hepatitis B, highlighting its dual role in managing viral infections.

TDF can be combined with other anti-HIV medications to create effective treatment regimens, such as the once-daily pill Truvada, and can also be used prophylactically to prevent HIV transmission, either orally or as a topical gel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir: quo vadis anno 2012 (where is it going in the year 2012)? De Clercq, E.[2015]

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]

Truvada (FTC/TDF) is an effective preexposure prophylaxis (PrEP) for HIV, but only a small fraction of the 1.2 million adults who could benefit from it are currently using it, highlighting a gap in preventative care.

The article emphasizes the importance of primary care providers (PCPs) in discussing and prescribing PrEP, aiming to enhance their confidence in managing patient care for high-risk groups to further reduce HIV incidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PrEParing for Preexposure Prophylaxis. Zappas, MP., Foreman, RM.[2021]

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]

The combination of emtricitabine and tenofovir alafenamide (F/TAF) is shown to be as effective as the traditional F/TDF combination in preventing HIV acquisition, with some evidence suggesting it may be even more effective.

F/TAF has a better safety profile, particularly regarding kidney health, making it a potentially safer option for older individuals, although it is associated with weight gain and has not yet been tested for all routes of HIV exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the combination of emtricitabine/ tenofovir alafenamide fumarate to reduce the risk of sexually acquired HIV-1-infection in at-risk adults. Mesplède, T.[2022]

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 alafenamide-emtricitabine (F/TAF) is a safer option for HIV preexposure prophylaxis (PrEP) compared to tenofovir disoproxil fumarate-emtricitabine (F/TDF), with F/TAF potentially averting 2101 fractures and 25 cases of end-stage renal disease (ESRD) over five years for 123,610 men who have sex with men (MSM) using PrEP.

The maximum price that payers should be willing to pay for F/TAF over generic F/TDF is estimated at $8670 per year, reflecting its improved safety profile, which is valued at no more than an additional $370 per person per year when considering the cost-effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Pricing of Branded Tenofovir Alafenamide-Emtricitabine Relative to Generic Tenofovir Disoproxil Fumarate-Emtricitabine for HIV Preexposure Prophylaxis: A Cost-Effectiveness Analysis. Walensky, RP., Horn, T., McCann, NC., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6453722/

Review of real-world implementation data on emtricitabine ... Patients should be made aware that PrEP is not 100% effective and will not prevent the acquisition of HIV strains resistant to FTC and TDF. Cost effectiveness.

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2816036

HIV Preexposure Prophylaxis With Emtricitabine and ... These findings were consistent with modeling data that estimated an HIV risk reduction of 76% for 2 doses per week, 96% for 4 doses per week, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00458393

Study Details | NCT00458393 | Emtricitabine/Tenofovir ... This study will evaluate the safety and efficacy of chemoprophylaxis for HIV prevention in men who have sex with men (MSM) who are at high risk for HIV ...

4. infectiousdiseaseadvisor.com infectiousdiseaseadvisor.com/news/long-term-daily-prep-with-emtricitabine-tenofovir-alafenamide-for-hiv-prevention/

Long-Term Daily PrEP With FTC/TAF Highly Effective for ... Among patients who received FTC/TAF for at least 144 weeks, the rate of HIV infection was less than 1% (incidence rate [IR], 0.13 per 100 person ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38019657/

Tenofovir Douche as HIV Preexposure Prophylaxis ... - PubMed Conclusions: All 3 tenofovir douches achieved tissue tenofovir-diphosphate concentrations and colorectal antiviral effect exceeding oral TDF and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4755800/

Safety of Oral Tenofovir Disoproxil Fumarate-Based Pre- ... TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02213328

Acceptability, Safety, and Use of Daily Truvada Pre- ... The purpose of this study is to evaluate the acceptability, safety, and use of daily Truvada PrEP as part of a comprehensive HIV prevention package.

8. gilead.com gilead.com/news/news-details/2018/gilead-announces-new-data-on-the-impact-of-truvada-emtricitabine-and-tenofovir-disoproxil-fumarate-for-pre-exposure-prophylaxis-prep-on-the-number-of-hiv-diagnoses-in-the-united-states

Gilead Announces New Data on the Impact of Truvada® ... Data show that states with highest use of Truvada for PrEP had significant declines in new HIV infections.

9. sciencedirect.com sciencedirect.com/science/article/pii/S2055664020303125

How safe is TDF/FTC as PrEP? A systematic review and ... A previous meta-analysis of TDF/FTC compared to alternative tenofovir alafenamide (TAF)/FTC for treatment found no significant difference in safety endpoints ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12492902/

Long-term safety and efficacy of emtricitabine and tenofovir ... To our knowledge, this is the first trial to compare safety outcomes of emtricitabine and tenofovir alafenamide with emtricitabine and tenofovir disoproxil ...