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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how HIV affects the body when HIV medications are briefly paused. Participants will stop their antiretroviral therapy (ART), the treatment for HIV, to observe how the virus and body interact without medication. People with HIV who have been on ART for over a year and have stable virus levels might be suitable candidates. The study involves closely monitoring participants two to three times a week during the treatment pause, which typically lasts about three weeks.

As an unphased trial, this study provides a unique opportunity to contribute to understanding HIV management without medication.

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 prior data suggests that this treatment interruption is safe for individuals with HIV?

Research has shown that stopping HIV treatment can pose safety concerns. When individuals discontinue antiretroviral therapy (ART), the virus in their blood can increase rapidly, often within 16 days. Other studies suggest that stopping treatment might raise the risk of infections and, in some cases, even death. Over the years, individuals have paused their HIV treatments due to side effects and other issues.

While this might sound concerning, the study is closely monitored. Most participants will restart their treatment within three weeks, even if the virus does not return during that time. This careful approach helps manage any risks involved. This information can assist in weighing the pros and cons for those considering participation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Treatment Interruption approach for HIV because it explores the potential benefits of taking breaks from antiretroviral therapy (ART), which is the standard treatment for HIV. This method is different because it aims to reduce medication burden and potential side effects by allowing periods without drugs, potentially improving quality of life for patients. Additionally, understanding how the virus behaves during these interruptions could provide insights into long-term management strategies and the body's natural ability to control HIV.

What evidence suggests that this trial's treatment interruption could be effective for HIV?

This trial will study the effects of a Treatment Interruption Arm for HIV. Research has shown that when individuals with HIV stop taking their antiretroviral therapy (ART), the virus often rebounds in about 16 to 21 days, becoming detectable in the blood again. However, restarting ART usually allows most individuals to control the virus, halting its multiplication. Studies have found that ART treatments with integrase inhibitors, which help stop the virus from growing, effectively regain control over the virus after a treatment break. It is important to note that stopping ART increases the risk of the virus spreading, particularly during pregnancy. ^{2 3 6 7 8}

Who Is on the Research Team?

Steven J Deeks, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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, 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5360157/

ANTIRETROVIRAL THERAPY INTERRUPTION AMONG HIV ... A growing body of evidence confirms that population-level increases in exposure to antiretroviral therapy (ART) result in substantial reductions in HIV-related ...

2. nature.com nature.com/articles/s41467-025-56116-1

Time to HIV viral rebound and frequency of post-treatment ... The median time to pVL >50 copies/mL after ART interruption was 16 days (IQR: 13–25), while time to pVL >400 and >10,000 copies/mL was 21 (IQR: ...

3. jonathanlilab.bwh.harvard.edu jonathanlilab.bwh.harvard.edu/wp-content/uploads/2018/08/Lessons-learned-from-HIV-antiretroviral-treatment.pdf

Lessons learned from HIV antiretroviral treatment interruption ... For a variety of reasons, including participant risk, recent treatment interruption trials have frequently used time to viral rebound as the primary endpoint ...

4. unaids.org unaids.org/sites/default/files/2025-05/20250520_QA-ART-Interruption_0.pdf

Q&A on the impact of the interruption of treatment for ... Vertical transmission of HIV. Interrupting antiretroviral therapy during pregnancy significantly increases the risk of perinatal HIV.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39155436/

a systematic review and meta-analysis - PubMed - NIH The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10055812/

Causes of HIV Treatment Interruption during the Last 20 Years In conclusion, our data on more than 4400 PWH show that adverse events have represented the most frequent cause of treatment interruptions in ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1130634324000047

Analysis of antiretroviral therapy interruption in people ... The aim of the study was to determine the change in reasons for antiretroviral treatment discontinuation for 12 years.

8. frontiersin.org frontiersin.org/journals/public-health/articles/10.3389/fpubh.2023.1137132/full

Antiretroviral treatment interruption and resumption within ... Background: Treatment interruption has been found to increase the risk of opportunistic infections and death among HIV-positive adults, ...