Treatment Interruption for HIV

(SCOPE-ATI Trial)

Overseen By Michael Peluso, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must be taking: Antiretrovirals

Must not be taking: Immunomodulatory drugs

Disqualifiers: Pregnancy, Hepatitis B, Hepatitis C, others

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: 2

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to understand the interaction between HIV and the host at the earliest stages when HIV medications are paused. Volunteers with HIV will interrupt antiretroviral therapy (ART) and then have intensive studies preformed two to three times per week. Most will resume therapy within three weeks, even if the virus does not rebound during this time.

Do I have to stop taking my current medications for the trial?

Yes, you will need to pause your HIV medications (antiretroviral therapy) for this trial. The study involves interrupting these medications to understand their interaction with the virus.

What data supports the effectiveness of the drug Raltegravir (Isentress) for HIV treatment?

Raltegravir (Isentress) is effective in reducing HIV levels in the blood, even in patients who have tried many other HIV drugs. It is well-tolerated and has shown promising results when used as a first-line therapy or when switching from other treatments. ^{1 2 3 4 5}

Is the treatment interruption for HIV using Raltegravir (Isentress) safe for humans?

Raltegravir (Isentress) has been shown to be well tolerated and has a favorable safety profile in both adults and children with HIV-1 infection, based on multiple studies. ^{1 3 4 6 7}

How is the drug Raltegravir (Isentress) unique in treating HIV?

Raltegravir (Isentress) is unique because it is the first drug in a new class called integrase inhibitors, which target a different part of the HIV virus compared to other treatments. It is effective for patients with drug-resistant HIV and can be used in both treatment-experienced and treatment-naive patients, offering flexibility in administration without food restrictions. ^{1 3 4 8 9}

Research Team

Steven J Deeks, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults over 18 with HIV who've been on antiretroviral therapy (ART) for at least a year, have undetectable virus levels, and a CD4+ count above 350. They must use two contraception methods if they can have children and agree to counseling to prevent HIV spread. It's not for those with severe kidney or liver disease, active hepatitis B or C, recent cancer, heart issues, or using certain other drugs.

Inclusion Criteria

Screening CD4+ T-cell count >350 cells/uL

Screening plasma HIV RNA levels below level of detection (< 40-75 copies/mL), and all available determinations in past 12 months also below level of detection (blips allowed)

Willing to receive counseling regarding HIV transmission risk mitigation

Exclusion Criteria

I have severe liver problems or unstable liver disease.

I have had cancer in the last 5 years.

I am currently taking drugs that affect my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Interruption

Participants interrupt their antiretroviral therapy (ART) and undergo intensive sampling two to three times per week

3 weeks

2-3 visits per week (in-person)

Extended Treatment Interruption

Controllers may participate in an extended treatment interruption with less restrictive ART restart criteria

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment interruption

6 months

Treatment Details

Interventions

• Treatment Interruption Arm

Trial Overview The study examines what happens when people with HIV stop taking their ART medications temporarily. Participants will halt their treatment under close monitoring with frequent check-ups to see how the virus behaves and how the body responds without medication.

Participant Groups

Group I: Treatment Interruption Arm Experimental Treatment 1 Intervention

Treatment Interruption Arm is already approved in United States, European Union for the following indications:

Approved in United States as Isentress for:

• HIV infections

Approved in European Union as Isentress for:

• HIV infections

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Chan Zuckerberg Biohub

Collaborator

Trials

2

Recruited

640+

Findings from Research

Raltegravir (Isentress) is the first approved HIV integrase inhibitor, targeting a different viral enzyme than traditional treatments, making it effective for patients with drug-resistant HIV.

Recent data suggests that raltegravir is well-tolerated and shows promise as a first-line therapy and in switch strategies, indicating its potential for broader use beyond just heavily treatment-experienced patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic strategies for raltegravir. Garrido, C., Soriano, V., de Mendoza, C.[2015]

In a study of 87 HIV-1-infected patients who switched from enfuvirtide to raltegravir, 86.2% maintained undetectable viral loads (<50 copies/ml) after 48 weeks, demonstrating the efficacy of this switch in a clinical setting.

The switch also led to a significant increase in CD4(+) T cell counts, with a median increase of 41 to 64 cells/μl, indicating improved immune function without any withdrawals due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short communication: Effectiveness at 48 weeks of switching from enfuvirtide to raltegravir in virologically suppressed multidrug-resistant HIV type 1-infected patients in a Brazilian cohort. Westin, MR., Biscione, F., Ribeiro, KM., et al.[2018]

Raltegravir, now available in a chewable formulation, has been shown to effectively reduce HIV-1 RNA levels in treatment-experienced children and adolescents, with significant virologic improvements sustained for up to 48 weeks in a phase I/II clinical trial.

The treatment was generally well tolerated, and the new formulation allows for flexible dosing, making it a valuable option for managing HIV-1 in younger patients aged 2-18 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Raltegravir: a review of its use in the management of HIV-1 infection in children and adolescents. Perry, CM.[2022]

Raltegravir is the first integrase inhibitor approved for treatment-experienced adults with HIV, showing strong efficacy in suppressing HIV-1 RNA levels for up to 48 weeks in clinical studies.

The drug is well tolerated and can be taken twice daily with or without food, making it a convenient option for patients with resistant HIV strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Raltegravir: the first in a new class of integrase inhibitors for the treatment of HIV. Sayana, S., Khanlou, H.[2015]

In a study of 263 HIV-1-infected patients who switched to raltegravir (RAL), the treatment was well tolerated and maintained virological suppression, with only 2.3% experiencing virological failure after a median follow-up of 12.4 months.

The switch to RAL, primarily motivated by toxicity and convenience, also resulted in a significant increase in CD4+ T cell counts, indicating improved immune function in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching to raltegravir in virologically suppressed in HIV-1-infected patients: a retrospective, multicenter, descriptive study. Podzamczer, D., Martínez, E., Domingo, P., et al.[2019]

Raltegravir, when combined with optimized background therapy, showed a significant and sustained reduction in HIV viral load over 96 weeks, with 68% of patients achieving viral levels below 400 copies/mL at week 48, and 55% maintaining this at week 96.

The treatment was well tolerated, with only 4% of patients discontinuing due to adverse events, indicating a favorable safety profile for raltegravir in patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a Phase II study. Gatell, JM., Katlama, C., Grinsztejn, B., et al.[2022]

Raltegravir has shown a favorable safety profile in long-term studies, with fewer drug-related adverse events compared to efavirenz, making it a well-tolerated option for both treatment-naïve and treatment-experienced HIV patients.

Serious drug-related adverse events were rare, and while some side effects like rash and elevated creatine kinase were noted, they were generally less severe than those associated with other treatments, indicating that raltegravir is a safe choice for HIV therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety from the raltegravir clinical development program. Teppler, H., Brown, DD., Leavitt, RY., et al.[2021]

Raltegravir, the first integrase strand transfer inhibitor for HIV-1, has shown both safety and efficacy in treatment-naive and heavily pretreated patients, demonstrating potent and durable effects over 96 weeks in three phase III studies.

It has a favorable drug interaction profile, allowing it to be safely administered alongside various other medications without the need for dose adjustments, making it suitable for a diverse patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Raltegravir: the first HIV-1 integrase strand transfer inhibitor in the HIV armamentarium. Nguyen, BY., Isaacs, RD., Teppler, H., et al.[2019]

In a study of 215 adults using raltegravir over a median of 2.6 years, the drug was found to be safe and effective, with no significant hepatotoxicity observed even in patients with hepatitis co-infection.

Once-daily dosing of raltegravir was effective for patients with good adherence, and it was also safely used in pregnant women without complications, indicating its potential for broader use in diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five years' real-life experience with raltegravir in a large HIV centre. van Halsema, C., Whitfield, T., Lin, N., et al.[2016]

References

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

New therapeutic strategies for raltegravir. [2015]

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

Short communication: Effectiveness at 48 weeks of switching from enfuvirtide to raltegravir in virologically suppressed multidrug-resistant HIV type 1-infected patients in a Brazilian cohort. [2018]

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

Raltegravir: a review of its use in the management of HIV-1 infection in children and adolescents. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Raltegravir: the first in a new class of integrase inhibitors for the treatment of HIV. [2015]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Switching to raltegravir in virologically suppressed in HIV-1-infected patients: a retrospective, multicenter, descriptive study. [2019]

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

Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a Phase II study. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term safety from the raltegravir clinical development program. [2021]

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

Raltegravir: the first HIV-1 integrase strand transfer inhibitor in the HIV armamentarium. [2019]

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

Five years' real-life experience with raltegravir in a large HIV centre. [2016]