Imaging and Biopsy During Treatment Interruption for HIV/AIDS

Overseen By Corey W Lau, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Antiretrovirals

Must not be taking: Steroids, Anticonvulsants, Catecholamines

Disqualifiers: Pregnancy, Diabetes, Hepatitis, others

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

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

Compensation: Varies

Number of Visits: 6

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of a short pause in antiretroviral therapy (ART) for people with HIV. Researchers aim to observe changes in virus levels in the blood and lymph nodes during this break. Participants will be divided into two groups: one will continue ART, while the other will stop for up to 90 days to monitor the effects. The study seeks individuals who have been on ART with stable virus levels for at least three years. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

If you are in the group that stops ART, you will need to stop your antiretroviral therapy for up to 90 days. The protocol does not specify about other medications, but you should discuss with the study team if you are taking drugs that might interfere with the study.

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

Research has shown that people with HIV sometimes temporarily stop their medication, known as antiretroviral therapy (ART), to help scientists learn more about the virus. This process is called an analytical treatment interruption (ATI). Studies have found that this method is generally safe with careful monitoring. The main concern during ATI is the potential increase in HIV levels, so researchers closely monitor this.

In past studies, some participants experienced higher HIV levels during these breaks, but researchers closely monitored them and restarted ART if needed to ensure safety. This method has been used in several trials to understand how the virus behaves when treatment is paused and to explore potential cures.

While stopping ART carries risks, these studies are designed to manage those risks and keep participants safe. Participants undergo regular checks, and ART can be quickly restarted if necessary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the effects of an Acute Treatment Interruption (ATI) for HIV/AIDS. Unlike the standard approach where patients continuously take antiretroviral therapy (ART) to manage the virus, ATI involves temporarily halting ART to observe how the body responds. This unique protocol could provide insights into whether the immune system can control the virus without constant medication. By closely monitoring viral levels and immune response during the interruption, researchers hope to uncover new strategies for managing HIV/AIDS, potentially leading to treatments that require less frequent medication.

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

Research has shown that temporarily stopping HIV medication, known as antiretroviral therapy (ART), can help scientists understand how the body and HIV interact without the drugs' constant effect. In this trial, participants in the ATI arm will stop their ART medications, allowing researchers to study these interactions. Studies have found that during these breaks, the virus level in the blood can increase. This helps researchers understand the virus's behavior and can guide future treatment plans. Early results suggest that even though the virus level rises, it doesn't always cause immediate health problems if closely monitored. These findings are crucial for developing strategies that could lead to an HIV cure or better treatments. Participants in the other arm will continue their pre-study ART throughout the trial. ^{1 2 3 4 6}

Who Is on the Research Team?

Chuen-Yen C Lau, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with HIV, on ART for at least 3 years with low viral levels, and a CD4 count of >=350 cells/microliter. They must consent to genetic testing and allow future research use of their samples. Participants agree to stop ART for up to 90 days and use barrier contraception or abstain from sex until viral re-suppression post-ART.

Inclusion Criteria

Participants must be willing to use a barrier method of contraception or remain abstinent during ATI and after re-initiating ART until viral re-suppression is achieved to prevent pregnancy and transmission of HIV

Participants must have CD4 cell count >=350 cells/microliter

Participants must have established medical care outside NIH

Exclusion Criteria

Pregnant participants

I have a history of HIV-related brain issues.

Participants with known history of initiating ART during the first year of HIV infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline and Initial Imaging

Participants undergo initial PET/CT imaging and baseline assessments

Up to 45 days

1 visit (in-person)

Analytic Treatment Interruption (ATI)

Participants randomized to ATI will halt ART and undergo weekly monitoring and PET/CT scans

Up to 90 days

Weekly visits (in-person)

Continued ART Monitoring

Participants continuing ART will have follow-up PET/CT scans and biopsies

12-16 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Acute Treatment Interruption

Trial Overview

The study is examining the location of HIV-infected cells in individuals on ART by comparing two groups: one continues ART while undergoing PET/CT scans; the other stops ART temporarily for additional scans and frequent blood tests before resuming treatment.

How Is the Trial Designed?

Group I: ATI Experimental Treatment 1 Intervention

Participants randomized to ATI will halt their ART medications starting 2 weeks (more or less 3 days) after the first imaging visit. This plan will be discussed with participants during the baseline visit. Patients will be contacted 1-3 days prior to ATI initiation. ATI may be delayed or cancelled if there are new safety concerns. HIV plasma viral levels and CD4 counts will be monitored every week during the ATI phase. If a participant meets any of the ART restart criteria during the ATI phase, then they will discontinue ATI and restart ART. Participants who do not meet restart criteria will remain off ART and continue to be monitored weekly until they have been on ATI for 90 days, and then will restart ART.

Group II: Continue ART Active Control 1 Intervention

Participants will continue on their pre-study ART throughout the trial.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Analytic treatment interruptions (ATIs) are essential for evaluating new HIV cure strategies but carry significant risks, including documented cases of HIV transmission during these interruptions.

The paper proposes practical risk mitigation strategies for ATIs to protect study participants and their partners, which will be implemented in an upcoming clinical trial, highlighting the need for safety in HIV research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A collaborative, multidisciplinary approach to HIV transmission risk mitigation during analytic treatment interruption. Peluso, MJ., Dee, L., Campbell, D., et al.[2021]

Analytical antiretroviral treatment interruption (ATI) is crucial for HIV research as it helps assess the effectiveness of new therapies in achieving sustained viral suppression without ongoing antiretroviral therapy, but it also poses risks that need careful management.

A meeting of diverse stakeholders highlighted the need for standardized strategies in ATI trials to enhance their safety and efficacy, focusing on risk mitigation, criteria for resuming ART, and ethical considerations to protect participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations for analytical antiretroviral treatment interruptions in HIV research trials-report of a consensus meeting. Julg, B., Dee, L., Ananworanich, J., et al.[2023]

A survey of 442 people living with HIV (PLHIV) and 144 HIV healthcare providers (HHP) revealed that PLHIV are generally more optimistic about the possibility of an HIV cure within the next 10 years compared to HHP (55% vs. 19%).

While 60% of HHP would support their patients in enrolling in HIV cure trials, only a small percentage would actively promote participation, indicating a gap in communication and education about analytical treatment interruptions (ATI) and HIV cure research that needs to be addressed for both PLHIV and HHP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability, motivation and the prospect of cure for people living with HIV and their healthcare providers in HIV cure-focused treatment interruption studies. Lau, JSY., Smith, MZ., Allan, B., et al.[2021]

Analytical treatment interruption (ATI) in HIV-infected individuals who started antiretroviral therapy (ART) early does not lead to an increase in HIV reservoirs or cause immunologic abnormalities when ART is restarted.

These results support the use of ATI in clinical trials to assess sustained virologic remission in patients who began ART during the early phase of HIV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Treatment Interruption on HIV Reservoirs and Lymphocyte Subsets in Individuals Who Initiated Antiretroviral Therapy During the Early Phase of Infection. Huiting, ED., Gittens, K., Justement, JS., et al.[2020]

In a study of 112 HIV-infected patients, treatment interruption (TI) guided by CD4+ counts was found to be safe, as long as therapy was restarted before CD4+ counts dropped below 200 cells/mm3.

The duration of the first TI was influenced by the CD4+ count at the end of the interruption, indicating that monitoring CD4+ levels is crucial for managing treatment interruptions effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and factors predicting the duration of first and second treatment interruptions guided by CD4+ cell counts in patients with chronic HIV infection. Boschi, A., Tinelli, C., Ortolani, P., et al.[2006]

In a study of 23 ART-suppressed HIV-1-infected patients, a short-term analytical treatment interruption (ATI) lasting about 4 weeks led to increased plasma HIV levels and T-cell activation, along with a rise in cellular HIV DNA and RNA.

Resuming antiretroviral therapy (ART) after the ATI successfully re-suppressed plasma HIV levels and restored CD4+ T cell counts, but did not alter the overall levels of persistent cellular HIV RNA or total HIV DNA, indicating that the ATI did not affect the long-term reservoir of the virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analytical antiretroviral therapy interruption does not irreversibly change preinterruption levels of cellular HIV. Papasavvas, E., Lada, SM., Joseph, J., et al.[2020]

In a review of 22 studies involving 7104 HIV-1-infected individuals, the overall occurrence of adverse events (AEs) during analytical treatment interruptions (ATIs) was low at 3%, suggesting that ATIs may be a safe approach in HIV-1 cure research.

Studies with shorter follow-up intervals (≤14 days) reported no significant AEs, while those with longer intervals showed a higher rate of AEs (6%), indicating that close monitoring during ATIs can enhance safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-analysis of Treatment Interruptions in Human Immunodeficiency Virus (HIV) Type 1-infected Patients Receiving Antiretroviral Therapy: Implications for Future HIV Cure Trials. Stecher, M., Claßen, A., Klein, F., et al.[2021]

To effectively detect a 30% difference in viral reactivation frequency in HIV cure trials, a sample size of 120 participants per group is necessary, highlighting the need for larger studies to improve statistical power.

The study suggests that measuring viral load more frequently than weekly or extending ART interruptions beyond 5 weeks offers little statistical benefit, indicating that optimizing study design can minimize risks to participants while still providing reliable results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Balancing Statistical Power and Risk in HIV Cure Clinical Trial Design. Lau, JSY., Cromer, D., Pinkevych, M., et al.[2022]

In a study of 71 HIV-infected patients, treatment interruptions guided by CD4+ cell counts were found to be safe, with no AIDS-defining illnesses occurring during the follow-up period of about 28 months.

Patients who interrupted treatment maintained high CD4+ counts and could safely resume therapy without losing efficacy, achieving rapid viral suppression after restarting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4+ cell-count-guided treatment interruptions in chronic HIV-infected patients with good response to highly active antiretroviral therapy. Boschi, A., Tinelli, C., Ortolani, P., et al.[2019]

A pooled analysis of 53 participants from four studies revealed that higher viral loads during the acute phase of HIV-1 infection are linked to faster viral rebound after treatment interruption, indicating the importance of early viral load management.

Key factors influencing the time to viral rebound included pre-antiretroviral therapy viral load and the time taken to achieve viral suppression after starting ART, suggesting that early intervention may be crucial for long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute HIV-1 infection viremia associate with rebound upon treatment interruption. Mdluli, T., Li, Y., Pinyakorn, S., et al.[2023]

Analytical treatment interruption (ATI) is crucial for studying new HIV treatments, with recent trials focusing on shorter interruption phases and more frequent viral load monitoring to minimize the risk of prolonged viral replication.

Modern ATI trials measure outcomes like time to viral rebound and viral control, with study designs tailored to the specific scientific questions and mechanisms of the treatments being tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analytical Treatment Interruption in HIV Trials: Statistical and Study Design Considerations. Zheng, L., Tierney, C., Bosch, RJ.[2022]

Citations

1.

nature.com

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

Time to HIV viral rebound and frequency of post-treatment ...

Ryom L. et al. Major revision version 11.0 of the European AIDS Clinical Society Guidelines 2021. HIV Med. 23, 849–858 (2022).

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8251690/

Analytical Treatment Interruption in HIV Trials

Analytical Treatment Interruption in HIV Trials: Statistical and Study Design Considerations ... Ronald J Bosch. 1Center for Biostatistics in AIDS ...

3.

academic.oup.com

academic.oup.com/jid/article/231/2/e419/7887579

Early Viral Dynamics Predict Human Immunodeficiency Virus ...

Abbreviations: ACTG, AIDS Clinical Trials Group; ATI, analytic treatment interruption ... We used data from HIV treatment interruption ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11330850/

The impact of analytical treatment interruptions and trial ...

In this systematic review and meta‐analysis, we analysed recent studies to determine the proportion of people living with HIV participating in ATI cure‐related ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2352301824001577

Analytical treatment interruption in children living with HIV

Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure.

6.

cell.com

cell.com/med/fulltext/S2666-6340(22)00276-8

Acute HIV-1 infection viremia associate with rebound upon ...

∙ Mellors, J.W.. The need for treatment interruption studies and biomarker identification in the search for an HIV cure. AIDS. 2015; 29:1429- ...