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

Trial Summary

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 Tenofovir safe for humans?

Tenofovir, often combined with emtricitabine (as in Truvada), is generally considered safe for preventing HIV, with newer forms like tenofovir alafenamide showing an improved safety profile compared to older versions. ^{1 2 3 4 5}

How does the drug Rectal vs Oral Tenofovir for HIV Prevention differ from other HIV prevention options?

This treatment is unique because it compares the effectiveness of tenofovir when administered as a rectal douche versus the traditional oral pill form, offering a novel route of administration that could provide more localized protection for individuals at risk of rectal HIV transmission. ^{1 5 6 7 8}

What is the purpose of this trial?

This is a Phase 2, multi-site, two-period, open label randomized crossover (Period 1 and 2) study. Participants are randomized 1:1 to one of two 8-week on-demand product sequences - TFV douche then oral F/TDF or oral F/TDF then TFV douche - with a 2 to 4-week washout period in between. Domains of safety, acceptability, adherence, and PK/PD (sub-study only) are assessed for each product.

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

1. 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]

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

Genital Mucosal Drug Concentrations and anti-HIV Activity in Tenofovir-Based PrEP Products: Intravaginal Ring vs. Oral Administration. [2023]

3. United States 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. [2021]

4. England 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. [2022]

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

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

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

Tenofovir: quo vadis anno 2012 (where is it going in the year 2012)? [2015]

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

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

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

PrEParing for Preexposure Prophylaxis. [2021]