SmartSteps Intervention for HIV Prevention

(SmartSteps Trial)

Overseen by Peter R Chai, MD MMS

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Fenway Community Health

Must be taking: PrEP

Disqualifiers: Crohn's, Ulcerative colitis, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a single-arm, observational study of HIV-negative MSM with substance use disorder. Those who meet pre-screening criteria will attend a Screening Visit (Visit 1), where the informed consent process will be conducted and study eligibility will be confirmed. Eligible participants will attend three additional visits over the course of the study - the Enrollment Visit (Visit 2), Month 1 Visit (Visit 3), and Month 2 Visit (Visit 4). Participants will take one PrEP digital pill per day, for 60 days total, while using the digital pill system (DPS) and Beiwe, a digital phenotyping app. On nonadherent days, participants will receive brief surveys prompting them to report the reasons for their missed dose, as well as their engagement in substance use and sexual activity. Timeline followback will be conducted at the Month 1 and Month 2 Visits to understand the context of any nonadherence. Qualitative user experience exit interviews and dried blood spots (DBS) will be conducted at the Month 2 Visit.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on PrEP or starting PrEP to participate.

What data supports the effectiveness of the drug Truvada for HIV prevention?

Research shows that Truvada, which contains tenofovir disoproxil fumarate and emtricitabine, is effective in preventing HIV when used as pre-exposure prophylaxis (PrEP). It has been shown to reduce the risk of HIV acquisition, especially when taken consistently. ^{1 2 3 4 5}

Is the SmartSteps Intervention for HIV Prevention safe for humans?

The combination of emtricitabine and tenofovir, used in various forms like Truvada and Descovy, has been shown to be generally safe for HIV prevention in adults. Studies indicate improved kidney and bone safety with tenofovir alafenamide compared to tenofovir disoproxil fumarate. ^{4 6 7 8 9}

How is the drug Descovy or Truvada unique for HIV prevention?

Descovy and Truvada are unique because they are used as preexposure prophylaxis (PrEP) to prevent HIV infection in high-risk individuals. Descovy contains tenofovir alafenamide, which is a newer form of tenofovir that may have fewer side effects on the kidneys and bones compared to the older form, tenofovir disoproxil fumarate, found in Truvada. ^{2 9 10 11 12}

Research Team

Peter R Chai, MD MMS

Principal Investigator

Brigham and Women's Hopsital

Eligibility Criteria

This trial is for HIV-negative cisgender men who have sex with men and struggle with substance use, scoring moderate to high on a substance use screener. They must be 18 or older, own a smartphone, and either be on PrEP (HIV prevention medication) or starting it. Excluded are those with certain gastrointestinal conditions, allergies to digital pill components or PrEP, unwillingness to use the study's digital tools, non-English speakers, or those with specific medical histories.

Inclusion Criteria

HIV negative

I am 18 years old or older.

Qualifying laboratory testing for PrEP: Cr clearance in past 3 months, HBV vaccination, liver function tests

Exclusion Criteria

You are allergic to the medication used for pre-exposure prophylaxis (PrEP).

You are allergic to gelatin, silver, or zinc, which are used to make the digital pill.

I am not willing to use the DPS or Beiwe app.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Enrollment

Participants complete baseline assessments, receive training on the digital pill system and Beiwe app, and ingest their first digital pill dose under observation

1 visit

1 visit (in-person)

Treatment

Participants take one PrEP digital pill per day for 60 days, using the digital pill system and Beiwe app. Nonadherence is monitored with surveys and timeline followback discussions

8 weeks

2 visits (in-person)

Follow-up

Participants undergo qualitative exit interviews and dried blood spot testing to assess PrEP adherence and user experience

1 visit

1 visit (in-person)

Treatment Details

Interventions

• Beiwe (Device)
• Descovy or Truvada (Antiretroviral Therapy)
• ID-Cap System (Device)

Trial Overview The SmartSteps study observes how well individuals adhere to their daily PrEP regimen using a digital pill system and an app called Beiwe over two months. It aims to understand adherence patterns by sending surveys on days when doses are missed and collecting data about substance use and sexual activity.

Participant Groups

Group I: Digital Pills and Beiwe Experimental Treatment 3 Interventions

Participants will take one PrEP digital pill per day, for 60 days total, while using the ID-Cap digital pill system and Beiwe digital phenotyping app.

Descovy or Truvada is already approved in Canada, Canada for the following indications:

Approved in Canada as Descovy for:

• Pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg

Approved in Canada as Truvada for:

• Pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg
• Treatment of HIV-1 infection in adults and pediatric patients weighing at least 17 kg

Who Is Running the Clinical Trial?

Fenway Community Health

Lead Sponsor

Trials

36

Recruited

5,833,000+

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Dr. William Curry

Brigham and Women's Hospital

Chief Medical Officer

MD from Columbia University College of Physicians and Surgeons

Dr. Scott Schissel

Brigham and Women's Hospital

Chief Executive Officer since 2021

MD from Columbia University College of Physicians and Surgeons

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

The Fenway Institute

Collaborator

Trials

15

Recruited

2,900+

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]

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]

In a study of women aged 18-35 in Durban, South Africa, daily oral PrEP (tenofovir disoproxil fumarate/emtricitabine) showed an overall mean adherence of 63%, highlighting the importance of adherence for effective HIV prevention during periconception.

Four distinct adherence patterns were identified: high steady adherence (22%), moderate steady adherence (31%), initially high but declining adherence (21%), and initially moderate with a rebound (26%), suggesting that targeted strategies are needed to maintain high adherence levels over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to daily, oral TDF/FTC PrEP during periconception among HIV-exposed South African women. Hurwitz, KE., Isehunwa, OO., Hendrickson, KR., et al.[2023]

In a phase 3 trial with 663 HIV-infected adults, switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) showed similar effectiveness in maintaining viral suppression, with 88.6% of TAF users and 89.1% of TDF users achieving HIV-1 RNA levels below 50 copies per milliliter after 96 weeks.

Patients switching to TAF experienced improvements in kidney function and bone mineral density compared to those remaining on TDF, indicating that TAF may offer a safer profile with better long-term health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults. Raffi, F., Orkin, C., Clarke, A., et al.[2022]

In the FEM-PrEP trial involving seroconverting women, there was no significant difference in HIV-1 RNA levels or CD4+ T-cell counts between those on PrEP and those on placebo, indicating that PrEP did not lead to better outcomes in these measures.

While no tenofovir resistance was found, FTC resistance was detected in some participants, suggesting that infections may have occurred before starting PrEP, rather than as a result of low adherence to the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug resistance and plasma viral RNA level after ineffective use of oral pre-exposure prophylaxis in women. Grant, RM., Liegler, T., Defechereux, P., et al.[2022]

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]

In a phase 3 study involving 5387 participants, daily emtricitabine and tenofovir alafenamide was found to be non-inferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention, with a lower incidence of HIV infections in the tenofovir alafenamide group (0.16 vs 0.34 infections per 100 person-years).

The tenofovir alafenamide regimen demonstrated better safety profiles, showing superior outcomes in bone mineral density and renal biomarkers compared to the tenofovir disoproxil fumarate regimen, with low rates of adverse events leading to discontinuation in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Mayer, KH., Molina, JM., Thompson, MA., et al.[2022]

In a study using macaques, daily preexposure prophylaxis (PrEP) with Truvada was shown to effectively protect against an HIV mutant resistant to FTC, with all treated animals remaining uninfected after exposure, while all untreated controls became infected.

The protection observed may be due to increased susceptibility of the virus to tenofovir, residual antiviral effects of FTC, and reduced virus fitness from the M184V mutation, indicating that Truvada can still be effective even against resistant strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protection against rectal transmission of an emtricitabine-resistant simian/human immunodeficiency virus SHIV162p3M184V mutant by intermittent prophylaxis with Truvada. Cong, ME., Youngpairoj, AS., Zheng, Q., et al.[2021]

Emtricitabine/tenofovir disoproxil fumarate (Truvada) has been approved as an effective preexposure prophylaxis (PrEP) therapy for adults at high risk of acquiring HIV through sexual contact.

The article reviews data that supports the efficacy of PrEP, highlighting its role in preventing HIV infection in high-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preexposure prophylaxis: An emerging clinical approach to preventing HIV in high-risk adults. Blackwell, CW.[2015]

In a study involving 121 individuals who seroconverted to HIV, those using the combination of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) had a higher rate of resistance mutations (57%) compared to those using tenofovir alone (5.3%), indicating that FTC may increase the risk of resistance during breakthrough infections.

Resistance mutations were more likely to occur when PrEP was initiated during an undetected acute HIV infection, highlighting the importance of screening for HIV before starting PrEP to minimize the risk of treatment failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent preexposure prophylaxis. Lehman, DA., Baeten, JM., McCoy, CO., et al.[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]

Daily oral PrEP with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is effective for men who have sex with men, but its effectiveness in cisgender women has been inconsistent, highlighting the need for diverse HIV prevention options.

Newer strategies like injectable long-acting cabotegravir have shown superior effectiveness compared to daily oral TDF/FTC, and ongoing studies are exploring other formulations like islatravir and lenacapavir, which may offer more flexible and effective prevention methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and Opportunities for Preexposure Prophylaxis. Cambou, MC., Landovitz, RJ.[2021]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Adherence to daily, oral TDF/FTC PrEP during periconception among HIV-exposed South African women. [2023]

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

Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults. [2022]

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

Drug resistance and plasma viral RNA level after ineffective use of oral pre-exposure prophylaxis in women. [2022]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. [2022]

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

Protection against rectal transmission of an emtricitabine-resistant simian/human immunodeficiency virus SHIV162p3M184V mutant by intermittent prophylaxis with Truvada. [2021]

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

Preexposure prophylaxis: An emerging clinical approach to preventing HIV in high-risk adults. [2015]

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

Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent preexposure prophylaxis. [2022]

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

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

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

Challenges and Opportunities for Preexposure Prophylaxis. [2021]