SmartSteps Intervention for HIV Prevention

(SmartSteps Trial)

Overseen By Georgia Goodman, BS

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Fenway Community Health

Must be taking: PrEP

Disqualifiers: Crohn's, Ulcerative colitis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 8 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a daily digital pill for HIV prevention among HIV-negative men who have sex with men. Participants will use a smart pill system and a smartphone app to track their medication and gather information about their habits and adherence to the treatment. The study aims to evaluate the effectiveness and user-friendliness of this combination for individuals at risk of HIV who also have a substance use disorder. Those who are HIV-negative, already on PrEP (pre-exposure prophylaxis, such as Descovy or Truvada) or starting it, and own a smartphone are suitable candidates. Participants should also be comfortable with technology and willing to provide feedback. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking HIV prevention method.

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.

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

Research shows that the digital pill system (ID-Cap System) is safe, effectively tracking 92% of expected doses. It operates well without causing problems for users. The FDA has cleared the system, confirming it meets safety standards.

Regarding the Beiwe app, studies indicate user acceptance. The app collects data from smartphones to understand behavior and medication habits. It is designed to help, not harm, and no evidence suggests it causes harm.

The treatments in this trial, Descovy and Truvada, are both FDA-approved for preventing HIV, indicating they have been tested for safety and are generally well-tolerated. Some people might experience mild side effects, but serious issues are rare.

Overall, based on previous research and approvals, the components of this trial appear safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the SmartSteps intervention for HIV prevention because it combines existing HIV prevention drugs, Descovy or Truvada, with cutting-edge digital technology. Unlike traditional methods where adherence is tracked manually, this approach uses the ID-Cap digital pill system and the Beiwe digital phenotyping app to monitor medication intake in real-time. This innovative delivery method allows for precise tracking of daily pill consumption, offering potential improvements in adherence and personalized feedback, which could significantly enhance the effectiveness of HIV prevention strategies.

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

Research has shown that taking Descovy or Truvada as PrEP (pre-exposure prophylaxis) can almost completely prevent HIV if taken regularly. In this trial, participants will use the ID-Cap System, which tracks pill intake and is well-liked for aiding adherence to medication schedules. A tiny sensor confirms when a pill is swallowed, simplifying medication tracking. Additionally, participants will use the Beiwe app, which collects data on smartphone use to understand habits affecting medication adherence. Together, these tools aim to improve adherence to PrEP plans, enhancing the treatment's effectiveness in preventing HIV. ^{1 3 4 6 7}

Who Is on the Research Team?

Peter R Chai, MD MMS

Principal Investigator

Brigham and Women's Hopsital

Are You a Good Fit for This Trial?

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

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

I am a cisgender male.

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Beiwe
• Descovy or Truvada
• ID-Cap System

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States 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 United States 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

Approved in European Union 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 European Union 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

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+

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. reporter.nih.gov reporter.nih.gov/search/3IUGDsMY9kOKHYPzjarW9g/project-details/10468388

Smart Steps - NIH RePORTER We will utilize a digital phenotyping app, Beiwe, which securely and anonymously collects raw smartphone use data. We will recruit N=40 MSM with substance ...

2. hsph.harvard.edu hsph.harvard.edu/research/onnela-lab/digital-phenotyping-and-beiwe-research-platform/

Digital Phenotyping and Beiwe Research Platform We define digital phenotyping as the “moment-by-moment quantification of the individual-level human phenotype in situ using data from personal digital devices,” ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10883553/

Acceptance of digital phenotyping linked to a digital pill ... Acceptance of digital phenotyping linked to a digital pill system to measure PrEP adherence among men who have sex with men with substance use.

4. medrxiv.org medrxiv.org/content/10.1101/2022.05.17.22275182v1.full-text

Increasing the Value of Digital Phenotyping Through ... Digital phenotyping data quality is a moving target that requires ongoing technical and protocol efforts to minimize missingness.

5. researchgate.net researchgate.net/publication/378712717_Smartphone_and_Wearable_Device-Based_Digital_Phenotyping_to_Understand_Substance_use_and_its_Syndemics

Smartphone and Wearable Device-Based Digital ... Daily oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, though efficacy depends on adherence. Digital pill ...

6. hsph.harvard.edu hsph.harvard.edu/research-resource/beiwe/

Beiwe Service Center The Beiwe Service Center enables researchers to access the open‑source Beiwe platform for smartphone‑based digital phenotyping—complete with Android/iOS apps ...

7. journals.sagepub.com journals.sagepub.com/doi/10.1177/14614448231158653

mHealth and social mediation: Mobile support among ... In this study, we examined the use and utility of one such app designed to support people living with HIV (PLWH) and SUD.