TRAncenDS for HIV

(TRAnscenDS Trial)

Overseen By CORINA T LELUTIU-WEINBERGER, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Columbia University

Disqualifiers: Non-Ryan White clinics, others

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

Compensation: Varies

Number of Visits: 6

2400 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the treatment TRANcendS for HIV?

The research highlights that certain antiretroviral therapies, like those including efavirenz, have shown better clinical outcomes in terms of virological suppression, which is crucial for effective HIV treatment. Additionally, strategies such as timely initiation of antiretroviral therapy and maximizing adherence have been shown to improve treatment outcomes, which could be relevant to the effectiveness of TRANcendS. ^{1 2 3 4 5}

What safety data exists for TRAncenDS (TRANcendS) treatment in humans?

The safety data from various studies on gene-modified T cell products, including those for HIV and cancer, show no evidence of replication-competent retrovirus (RCR) in patients, suggesting a strong safety profile. Additionally, the risk of developing RCR is extremely low, with estimates indicating it would take over 50 years to observe a single case, highlighting the treatment's general safety in humans. ^{6 7 8 9 10}

How does the drug TRAncenDS for HIV differ from other treatments?

TRAncenDS, also known as enfuvirtide, is unique because it is a fusion inhibitor, which means it prevents the HIV virus from entering human cells, unlike other treatments that target the virus after it has entered the cell. This mechanism of action is different from the more common antiretroviral drugs that inhibit viral replication inside the cell. ^{11 12 13 14 15}

What is the purpose of this trial?

The scope of this study is to engage Ryan White HIV/AIDS Program (RWHAP) funded organizations in the South/East US to co-develop context-responsive programs to reduce structural racism and discrimination (SRD) against Black, Indigenous, People of Color (BIPOC) living with HIV (PLH) and BIPOC healthcare workers. Six RWHAP clinics will be selected to participate and be assigned to one of three sequences (two clinics per cluster). All members will complete participate in interactive trainings to raise awareness of and reduce SRD, from the clinic policy level, to attitudes, to the clinic environment. All clinic members and select patients will complete self-administered surveys every 6 months over 24 months.

Research Team

Corina Lelutiu-Weinberger, PhD

Principal Investigator

Columbia University

Felicia A Browne, ScD

Principal Investigator

RTI International

Eligibility Criteria

This trial is for Ryan White HIV/AIDS Program clinics in the South/East US, focusing on reducing structural racism and discrimination against BIPOC living with HIV and healthcare workers. Clinic leaders must show high motivation to participate, as indicated by specific survey scores.

Inclusion Criteria

Clinic leaders and staff will need to fill out two short surveys to see if their clinic is a good fit for the study. If the clinic scores high on most items, it can be considered for the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention Implementation

Implementation of the TRAnscenDS intervention across clinics, including workshops, interactive trainings, and learning circles to reduce structural racism and discrimination.

24 months

Multiple workshops and training sessions (virtual and in-person)

Follow-up

Participants are monitored for changes in intersectional stigma, depression, anxiety, and other outcomes every 6 months.

24 months

Surveys every 6 months

Treatment Details

Interventions

• TRANcendS

Trial Overview The TRAncenDS intervention is being tested across six selected clinics. It involves interactive trainings aimed at raising awareness and reducing structural racism and discrimination at various levels within the clinic environment over an 18-month period.

Participant Groups

Group I: Third Cluster Experimental Treatment 1 Intervention

The intervention will be implemented across three steps with a total of 6 clinics (two clinics per step). The earliest roll-out of the intervention will be at the clinics randomized to Cluster 1. The intervention consists of a mix of Workshops, Interactive Trainings and Learning Circles (virtual and in-person). In the first workshop, the investigators will present baseline findings to all clinic members to 1) raise awareness for the need for intervention to reduce Structural Racism and Discrimination (SRD) , 2) facilitate collaborative processes, 3) catalyze change for practice transformation, to 4) guide the intervention process. This workshop will be followed by a series of interactive trainings covering topics from the history of structural racism, to intersectional stigma and discrimination, bias, systems of accountability, and the creation of a manual to guide the implementation and sustainability of SRD reduction efforts.

Group II: Second Cluster Experimental Treatment 1 Intervention

The intervention will be implemented across three steps with a total of 6 clinics (two clinics per step). The earliest roll-out of the intervention will be at the clinics randomized to Cluster 1. The intervention consists of a mix of Workshops, Interactive Trainings and Learning Circles (virtual and in-person). In the first workshop, the investigators will present baseline findings to all clinic members to 1) raise awareness for the need for intervention to reduce Structural Racism and Discrimination (SRD) , 2) facilitate collaborative processes, 3) catalyze change for practice transformation, to 4) guide the intervention process. This workshop will be followed by a series of interactive trainings covering topics from the history of structural racism, to intersectional stigma and discrimination, bias, systems of accountability, and the creation of a manual to guide the implementation and sustainability of SRD reduction efforts.

Group III: First Cluster Experimental Treatment 1 Intervention

The intervention will be implemented across three steps with a total of 6 clinics (two clinics per step). The earliest roll-out of the intervention will be at the clinics randomized to Cluster 1. The intervention consists of a mix of Workshops, Interactive Trainings and Learning Circles (virtual and in-person). In the first workshop, the investigators will present baseline findings to all clinic members to 1) raise awareness for the need for intervention to reduce Structural Racism and Discrimination (SRD) , 2) facilitate collaborative processes, 3) catalyze change for practice transformation, to 4) guide the intervention process. This workshop will be followed by a series of interactive trainings covering topics from the history of structural racism, to intersectional stigma and discrimination, bias, systems of accountability, and the creation of a manual to guide the implementation and sustainability of SRD reduction efforts.

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

National Institute of Nursing Research (NINR)

Collaborator

Trials

623

Recruited

10,400,000+

Rutgers University

Collaborator

Trials

127

Recruited

2,814,000+

Florida State University

Collaborator

Trials

234

Recruited

41,100+

RTI International

Collaborator

Trials

201

Recruited

942,000+

Findings from Research

Only 31% of people in need of antiretroviral therapy in sub-Saharan Africa are currently receiving it, highlighting a significant gap in treatment access that needs to be addressed to combat HIV effectively.

Key strategies to improve HIV treatment outcomes include scaling up testing, timely initiation of therapy, and enhancing patient adherence and retention in care, which are essential for reducing opportunistic infections and improving overall quality of life for those living with HIV/AIDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies to optimize HIV treatment outcomes in resource-limited settings. Nakanjako, D., Colebunders, R., Coutinho, AG., et al.[2022]

Between 1996 and 2010, the introduction of new first-line cART regimens in the Netherlands led to significant improvements in viral load suppression and CD4 cell recovery among HIV patients, indicating enhanced efficacy of treatment.

Although mortality rates remained stable, the incidence of patients needing to switch regimens due to virological failure or toxicity decreased by more than half, suggesting that newer treatments are better tolerated and more effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in first-line cART regimens and short-term clinical outcome between 1996 and 2010 in The Netherlands. Smit, M., Smit, C., Geerlings, S., et al.[2022]

In a study of 6259 patients starting highly active antiretroviral therapy (HAART) from 2000 to 2010, those treated with efavirenz (EFV) had significantly better outcomes, achieving a composite outcome of success (COS) more frequently than those on boosted protease inhibitors (PIs).

Patients on boosted PIs not only had lower rates of virological suppression but also developed AIDS more frequently and had higher mortality rates compared to those on EFV, highlighting the efficacy and safety advantages of EFV in HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort. Postorino, MC., Prosperi, M., Quiros-Roldan, E., et al.[2020]

In a study of 3128 patients starting first-line antiretroviral therapy (ART) in France, treatment failure rates were 25% at 12 months and 42% at 24 months, indicating a significant challenge in long-term HIV management.

Patients on the TDF/FTC/EFV regimen experienced higher treatment failure rates at 12 months compared to those on TDF/FTC with DRV/r, suggesting that efavirenz-based regimens may be less effective in the short term, although no significant differences were observed at 24 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of First Antiretroviral Regimens in Clinical Practice Using a Causal Approach. Cuzin, L., Pugliese, P., Allavena, C., et al.[2022]

The study used a mathematical simulation model based on data from the ATHENA cohort to analyze differences in mortality rates among HIV treatment centers in The Netherlands, revealing that the distribution of CD4 counts at the time of care entry is a key factor influencing survival rates.

By encouraging earlier treatment for HIV-infected individuals, specifically aiming for a CD4 count of at least 400 cells/mm³ at entry, the model predicts a potential 20% reduction in mortality during the first three years of combination anti-retroviral therapy (cART).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late entry to HIV care limits the impact of anti-retroviral therapy in The Netherlands. Smit, C., Hallett, TB., Lange, J., et al.[2021]

A review of 2905 individual case safety reports (ICSRs) for axi-cel, a CAR-T-cell therapy for B-cell lymphomas, revealed that about 80% of reported adverse events were serious, with significant risks of nervous system and immune system disorders.

The data suggests that axi-cel may have a higher incidence of neurotoxic effects compared to other CAR-T therapies, indicating a need for careful monitoring of these side effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pharmacovigilance Study on the Safety of Axicabtagene Ciloleucel Based on Spontaneous Reports from the EudraVigilance Database. Rafaniello, C., Liguori, V., Zinzi, A., et al.[2023]

In a study involving 737 patients across 60 clinical trials, no evidence of replication competent retrovirus (RCR) was found in 1,595 post-treatment blood samples, supporting the safety of gammaretroviral vectors used in gene therapy.

The majority of the trials (93%) focused on cancer immunotherapy, and the results indicate that current manufacturing methods effectively produce RCR-free products, reinforcing the overall safety profile of retroviral gene therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials. Cornetta, K., Yao, J., House, K., et al.[2023]

In a review of 646 adverse event reports for the CAR T-cell therapy tisagenlecleucel from August 2017 to August 2019, the most common adverse event was cytokine release syndrome (CRS), reported in 51.1% of cases, with a serious outcome in over 95% of reports.

Despite the high reporting rate of adverse events (81.0%), most deaths (64%) were due to the progression of the underlying disease rather than the therapy itself, indicating that no new safety concerns were identified post-marketing, and the rates of CRS and neurotoxicity were lower than those observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events reported to the U.S. Food and Drug Administration Adverse Event Reporting System for tisagenlecleucel. Dores, GM., Jason, C., Niu, MT., et al.[2021]

In a study involving 375 manufactured T cell products and 308 patients, there was no evidence of replication-competent retrovirus/lentivirus (RCR/L), indicating a strong safety profile for gene-modified cell therapies in HIV and oncology.

The data suggests that patients would need to be monitored for over 52 years to potentially observe an RCR/L event, and the time for lentivirus-modified T cell products to fall below the threshold for vector integration site analysis is relatively short, ranging from 0.66 to 1.4 months depending on the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retroviral and Lentiviral Safety Analysis of Gene-Modified T Cell Products and Infused HIV and Oncology Patients. Marcucci, KT., Jadlowsky, JK., Hwang, WT., et al.[2019]

In a review of 996 adverse events related to CAR T cell therapy from 2017 to 2019, 19.7% were cardiovascular events (CVEs), with arrhythmias being the most common, indicating a significant risk associated with this treatment.

Patients experiencing CVEs had a higher mortality rate of 30.1%, highlighting the need for careful monitoring for cardiovascular issues, especially in those also presenting with neurotoxicity or cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis. Guha, A., Addison, D., Jain, P., et al.[2021]

In a study of 187 HIV-infected patients over an average of 19.4 months, enfuvirtide treatment led to a significant mean increase of approximately 102 CD4+ cells/mm³, regardless of the patients' initial CD4+ cell counts.

Patients starting enfuvirtide with CD4+ counts below 100 cells/mm³ did not reach the same CD4+ levels as those starting with higher counts, suggesting that initiating treatment at higher CD4+ levels may provide better immunologic benefits, even if complete viral suppression is not achieved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunologic benefits of enfuvirtide in patients enrolled in a drug assistance program. Saberi, P., Caswell, NH., Gruta, CI., et al.[2018]

In a study of 74 HIV-1-infected children and adolescents treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for at least 6 months, 37.8% experienced virological failure, particularly those with poor viral suppression at baseline, highlighting the importance of monitoring treatment adherence.

BIC/FTC/TAF demonstrated a high genetic barrier to resistance, with only one case of a mutation observed, suggesting it is a promising treatment option for pediatric patients who may struggle with adherence and virological control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bictegravir/emtricitabine/tenofovir alafenamide in paediatrics: Real-life experience from a French cohort (2019-2023). Frange, P., Veber, F., Burgard, M., et al.[2023]

In a study of HIV-1 strains from patients in the Luxembourg HIV Cohort, primary resistance to the fusion inhibitor enfuvirtide (T-20) was found to be rare, with no classic resistance mutations identified in either subtype B or non-B isolates.

Although no major resistance mutations were detected, some uncommon mutations were observed in specific residues of the gp41 protein, suggesting that while T-20 resistance is uncommon, further research is needed to understand these variations and their potential impact on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uncommon mutations at residue positions critical for enfuvirtide (T-20) resistance in enfuvirtide-naive patients infected with subtype B and non-B HIV-1 strains. Roman, F., Gonzalez, D., Lambert, C., et al.[2020]

The combination of dolutegravir (DTG) and lamivudine (3TC) has shown promising efficacy in treating HIV, with 90% of participants in the PADDLE study achieving viral suppression below 50 copies/mL.

In phase III studies (GEMINI-1 and -2) involving 1,433 treatment-naive adults, the DTG + 3TC regimen demonstrated noninferior efficacy compared to a traditional three-drug regimen, with a better safety profile and no emergence of drug resistance mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dolutegravir plus lamivudine dual therapy - a new option for initial antiretroviral therapy. Fida, M., Rizza, SA., Temesgen, Z.[2020]

In a study of 55 antiretroviral-naive patients recently infected with HIV-1, two cases of primary resistance to the fusion inhibitor enfuvirtide (T20) were identified, marking the first evidence of such resistance in this population.

The overall prevalence of transmitted HIV-1 resistance in the cohort was 20%, highlighting the need for ongoing surveillance of drug-resistant HIV-1 variants, including those resistant to T20.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary resistance to enfuvirtide (T20) in recently HIV-1 infected, antiretroviral-naive patients from the ANRS Aquitaine Cohort. Peuchant, O., Capdepont, S., Ragnaud, JM., et al.[2022]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Strategies to optimize HIV treatment outcomes in resource-limited settings. [2022]

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

Changes in first-line cART regimens and short-term clinical outcome between 1996 and 2010 in The Netherlands. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort. [2020]

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

Comparative Effectiveness of First Antiretroviral Regimens in Clinical Practice Using a Causal Approach. [2022]

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

Late entry to HIV care limits the impact of anti-retroviral therapy in The Netherlands. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A Pharmacovigilance Study on the Safety of Axicabtagene Ciloleucel Based on Spontaneous Reports from the EudraVigilance Database. [2023]

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

Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials. [2023]

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

Adverse events reported to the U.S. Food and Drug Administration Adverse Event Reporting System for tisagenlecleucel. [2021]

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

Retroviral and Lentiviral Safety Analysis of Gene-Modified T Cell Products and Infused HIV and Oncology Patients. [2019]

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

Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis. [2021]

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

Immunologic benefits of enfuvirtide in patients enrolled in a drug assistance program. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Bictegravir/emtricitabine/tenofovir alafenamide in paediatrics: Real-life experience from a French cohort (2019-2023). [2023]

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

Uncommon mutations at residue positions critical for enfuvirtide (T-20) resistance in enfuvirtide-naive patients infected with subtype B and non-B HIV-1 strains. [2020]

14. Spain pubmed.ncbi.nlm.nih.gov

Dolutegravir plus lamivudine dual therapy - a new option for initial antiretroviral therapy. [2020]

15. England pubmed.ncbi.nlm.nih.gov

Primary resistance to enfuvirtide (T20) in recently HIV-1 infected, antiretroviral-naive patients from the ANRS Aquitaine Cohort. [2022]