iENGAGE Program for HIV Infection

Overseen By MICHELE JEAN-GILLES, PHD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Florida International University

Disqualifiers: Virally suppressed

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

66 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug iENGAGE for HIV infection?

Research shows that tenofovir alafenamide (TAF), a component of iENGAGE, is effective in treating HIV and has a better safety profile for kidneys and bones compared to an older version of the drug. Studies also indicate that TAF is effective in maintaining viral suppression in people with HIV, including those aged 65 and older. ^{1 2 3 4 5}

Is tenofovir alafenamide (TAF) safe for humans?

Tenofovir alafenamide (TAF) is generally considered safe for humans, with studies showing it has improved kidney and bone safety compared to an older version, tenofovir disoproxil fumarate (TDF). It has been used safely in various HIV treatments, including in older adults and over long periods. ^{1 2 6 7 8}

What makes the iENGAGE drug unique for treating HIV?

The iENGAGE drug, which includes tenofovir alafenamide (TAF), is part of a single-tablet regimen that combines multiple medications into one pill, making it easier for patients to adhere to their treatment. It features an unboosted integrase strand transfer inhibitor, which has a high barrier against resistance, and is effective in managing HIV with fewer side effects, especially in patients with other health conditions like kidney or bone issues. ^{9 10 11 12 13}

What is the purpose of this trial?

The goal of this clinical trial is to test a culturally tailored engagement and retention intervention for Haitian Immigrants Living With HIV (HILWH). The main questions it aims to answer are: * Does this intervention result in measurable engagement and retention in care? * Does this intervention result in measurable viral suppression within 6 months? Participants will * participate in a pilot health intervention entailing 4 individual meetings, approximately once monthly over a six-month period and completing research questionnaires at enrollment, post-intervention and at 6 months post-enrollment. * Six participants who have completed the pilot intervention and agree to take part, will participate in the photovoice portion of the study. This activity will consist of 6 additional meetings where participants will be taught about using photographs to illustrate their experience participating in the study and take and display photographs.

Eligibility Criteria

This trial is for Haitian immigrants in the U.S. who are HIV positive, either newly diagnosed within the last two months or not having their virus under control (non-virally suppressed).

Inclusion Criteria

You have tested positive for HIV.

I was diagnosed with HIV recently or my HIV is not under control.

You moved to the US from Haiti.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Enrollment and Baseline Assessment

Participants complete baseline assessments and are enrolled in the study

1 week

1 visit (in-person)

Pilot Health Intervention

Participants engage in a culturally tailored intervention with 4 individual meetings approximately once monthly over a six-month period

6 months

4 visits (in-person)

Post-Intervention Assessment

Participants complete post-intervention assessments

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for engagement and viral suppression at 6 months post-enrollment

6 months

1 visit (in-person)

Photovoice Activity (Optional)

Six participants engage in photovoice activities to illustrate their experiences, involving 6 additional meetings

2.5 months

6 visits (in-person)

Treatment Details

Interventions

• iENGAGE

Trial Overview The study tests a culturally tailored program called iENGAGE designed to help Haitian Immigrants Living With HIV stay engaged with care and achieve viral suppression. It includes four individual meetings over six months and questionnaires at different stages.

Participant Groups

Group I: Haitian immigrant iENGAGE (H-iENGAGE) intervention Experimental Treatment 1 Intervention

1. Enrollment; 2. Baseline assessment; 3. Upon baseline completion, scheduling of H-iENGAGE sessions 1 through 4 4. Following Session 4, conduct Process evaluation; 5. Post-intervention assessment; 6. Six-month follow up assessment\* \*Six participants will complete AIM 3: Identify multi-level implementation factors contributing to intervention outcomes, using photovoice in mixed methods. 7. End of study participation

iENGAGE is already approved in United States, European Union for the following indications:

Approved in United States as Tenofovir alafenamide for:

• HIV-1 infection
• Chronic hepatitis B virus infection

Approved in European Union as Tenofovir alafenamide for:

• HIV-1 infection
• Chronic hepatitis B virus infection

Who Is Running the Clinical Trial?

Florida International University

Lead Sponsor

Trials

114

Recruited

19,400+

Findings from Research

The single tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is as effective as the traditional TDF-based regimen for treating HIV in naive patients and shows improved efficacy in those switching from TDF-based treatments.

E/C/F/TAF demonstrates significant safety benefits, including improved renal function and bone mineral density compared to TDF, making it a promising option for enhancing the tolerability of HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide for the treatment of HIV in adults. Bonora, S., Calcagno, A., Trentalange, A., et al.[2021]

In a 48-week study involving 86 older adults with HIV, switching to the medication bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) resulted in a high rate of virologic suppression, with 90.7% of participants maintaining HIV-1 RNA levels below 50 copies/ml.

The treatment was well tolerated, with no serious adverse events related to the drug and a high adherence rate of 98.6%, indicating that B/F/TAF is a safe and effective option for older adults living with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People with HIV Aged ≥ 65 Years: Week 48 Results of a Phase 3b, Open-Label Trial. Maggiolo, F., Rizzardini, G., Molina, JM., et al.[2021]

Tenofovir alafenamide (TAF) is expected to revolutionize HIV-1 treatment due to its better safety profile compared to the older drug tenofovir disoproxil fumarate (TDF), making it suitable for both new and experienced patients.

TAF has already been included in international treatment guidelines for HIV-1, indicating its efficacy and acceptance in clinical practice, despite challenges related to budget constraints and varying global healthcare spending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Development Agenda on Tenofovir Alafenamide in Clinical Practice. Di Biagio, A., Riccardi, N., Rusconi, S., et al.[2021]

In a Phase 2 study involving 170 antiretroviral naive adults, both tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) showed high rates of virologic suppression in HIV-1 patients after 48 weeks, with 88.4% and 87.9% respectively achieving less than 50 copies of HIV RNA per milliliter.

Patients treated with TAF experienced significantly less impact on kidney function and bone mineral density compared to those treated with TDF, indicating a potentially safer profile for TAF in terms of renal and bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. Sax, PE., Zolopa, A., Brar, I., et al.[2022]

In a study of ART-naive adults, the tenofovir alafenamide (TAF) regimen showed similar viral suppression rates to the tenofovir disoproxil fumarate (TDF) regimen at 24 weeks, but had a slightly lower rate at 48 weeks due to higher discontinuation rates in the TAF group.

TAF demonstrated significantly better renal and bone safety profiles compared to TDF, with less proteinuria and less reduction in bone mineral density, making it a promising option for initial HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study. Mills, A., Crofoot, G., McDonald, C., et al.[2022]

In a study of 5888 patients across six randomized controlled trials, tenofovir alafenamide (TAF) showed similar viral suppression rates to tenofovir disoproxil fumarate (TDF) at 48 weeks, with TAF being particularly effective for patients switching from TDF regimens.

TAF demonstrated better safety profiles, with less impact on kidney function and bone density compared to TDF, making it a potentially safer option for both treatment-naive and experienced HIV-1 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in antiretroviral regimens for HIV-1 therapy: Meta-analysis. Wang, H., Lu, X., Yang, X., et al.[2022]

Tenofovir alafenamide (TAF) is a prodrug that achieves higher intracellular concentrations of tenofovir while maintaining lower serum levels, leading to similar efficacy in HIV-1 treatment compared to tenofovir disoproxil fumarate (TDF) but with reduced risks of kidney damage and bone density loss.

Clinical trials have confirmed that TAF-containing regimens provide effective virological suppression and have led to the approval of three combination products for HIV-1 management, making TAF a recommended option for initial treatment in antiretroviral-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir Alafenamide. Gibson, AK., Shah, BM., Nambiar, PH., et al.[2021]

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) demonstrated high efficacy in maintaining HIV-1 suppression, with 98.6% of participants achieving HIV-1 RNA levels below 50 copies/mL after 240 weeks of treatment.

The treatment was found to be safe, with only 1.6% of participants discontinuing due to adverse events, and no cases of treatment-emergent resistance were detected, indicating its long-term durability and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bictegravir/emtricitabine/tenofovir alafenamide as initial treatment for HIV-1: five-year follow-up from two randomized trials. Sax, PE., Arribas, JR., Orkin, C., et al.[2023]

The single-tablet regimen (STR) of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) has shown non-inferior virological efficacy compared to traditional dolutegravir-based regimens in treating HIV, based on large clinical trials over 96 weeks.

BIC/FTC/TAF is designed to be highly tolerable and has a high barrier against drug resistance, making it a promising option for managing HIV while also addressing associated comorbidities like cardiovascular disease and renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) single-tablet regimen in the expanding spectrum of fixed-dose combination therapy for HIV. Stellbrink, HJ., Lazzarin, A., Woolley, I., et al.[2021]

In a study of 60 patients receiving ifosfamide, 26.6% developed encephalopathy, with varying severity, indicating a notable risk of neurological symptoms associated with this treatment.

The study found no significant risk factors related to age or dosage that could predict encephalopathy, suggesting that individual patient predisposition plays a key role, and ifosfamide can be safely administered to older patients without increased neurotoxicity risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and severity of ifosfamide-induced encephalopathy. Rieger, C., Fiegl, M., Tischer, J., et al.[2019]

Mitonafide, a new compound with intercalative properties, was tested in a phase I study involving 30 patients, but the study was halted due to significant central nervous system toxicity observed at higher doses (above 118 mg/m2), including irreversible memory loss and confusion.

The toxicity was deemed dose-limiting and related to the short intravenous infusion schedule, leading to a recommendation against this administration method, while further studies with a longer administration schedule are currently being pursued.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of mitonafide in solid tumors. Llombart, M., Poveda, A., Forner, E., et al.[2019]

The combination of topotecan and ifosfamide as a salvage treatment for advanced ovarian cancer showed a 41% objective response rate in a study of 39 patients who had previously undergone platinum-based chemotherapy.

While the treatment was feasible, it resulted in moderate toxicity, including significant neutropenia and anemia, indicating that careful monitoring and management of side effects are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan and ifosfamide as salvage treatment in advanced ovarian cancer. Chiara, S., Tognoni, A., Pastrone, I., et al.[2013]

Intraperitoneal (i.p.) administration of gemcitabine was found to be tolerated within a range of doses (40-160 mg/m²) in 30 patients with peritoneal carcinomatosis, although some experienced dose-limiting toxicities such as nausea and respiratory issues.

The study demonstrated that gemcitabine achieves significantly higher concentrations in the peritoneal cavity compared to plasma, with a median peak concentration 1,116-fold higher, suggesting its potential effectiveness for treating conditions like optimally debulked ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of intraperitoneal gemcitabine in the treatment of advanced malignancies primarily confined to the peritoneal cavity. Morgan, RJ., Synold, TW., Xi, B., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide for the treatment of HIV in adults. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People with HIV Aged ≥ 65 Years: Week 48 Results of a Phase 3b, Open-Label Trial. [2021]

3. Spain pubmed.ncbi.nlm.nih.gov

A Comprehensive Development Agenda on Tenofovir Alafenamide in Clinical Practice. [2021]

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

Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. [2022]

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

Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study. [2022]

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

The efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in antiretroviral regimens for HIV-1 therapy: Meta-analysis. [2022]

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

Tenofovir Alafenamide. [2021]

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

Bictegravir/emtricitabine/tenofovir alafenamide as initial treatment for HIV-1: five-year follow-up from two randomized trials. [2023]

9. England pubmed.ncbi.nlm.nih.gov

The potential role of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) single-tablet regimen in the expanding spectrum of fixed-dose combination therapy for HIV. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Incidence and severity of ifosfamide-induced encephalopathy. [2019]

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

Phase I study of mitonafide in solid tumors. [2019]

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

Topotecan and ifosfamide as salvage treatment in advanced ovarian cancer. [2013]

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

Phase I trial of intraperitoneal gemcitabine in the treatment of advanced malignancies primarily confined to the peritoneal cavity. [2022]