Imaging and Biopsy During Treatment Interruption for HIV/AIDS

Overseen by Chuen-Yen C Lau, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must be taking: Antiretrovirals

Must not be taking: Steroids, Anticonvulsants, Catecholamines

Disqualifiers: Pregnancy, Diabetes, Hepatitis, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial uses special scans and tissue samples to find and study areas in the body where HIV might still be active in adults receiving ongoing HIV treatment.

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.

What data supports the effectiveness of the treatment Acute Treatment Interruption, Analytic Treatment Interruption, ATI for HIV/AIDS?

Research shows that stopping HIV treatment temporarily (ATI) does not increase the amount of HIV in the body or cause immune system problems when treatment is restarted. This suggests ATI can be safely used in studies to see if new treatments can control HIV without ongoing medication. ^{1 2 3 4 5}

Is it safe to participate in a clinical trial involving treatment interruption for HIV/AIDS?

Treatment interruptions in HIV trials, known as analytical treatment interruptions (ATI), can pose risks, including the potential for HIV transmission and discomfort from pausing medication. However, strategies are being developed to minimize these risks and ensure participant safety. ^{3 6 7 8 9}

How does the treatment interruption for HIV/AIDS differ from other treatments?

This treatment involves temporarily stopping antiretroviral therapy (ART) to assess if the body can control the virus without medication, which is different from continuous ART that is typically used to manage HIV. This approach, known as analytical treatment interruption (ATI), is unique because it helps researchers understand if a sustained virologic remission can be achieved without ongoing medication. ^{1 3 4 10 11}

Research Team

Chuen-Yen C Lau, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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

Trial Timeline

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)

Treatment Details

Interventions

• Acute Treatment Interruption (Other)

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.

Participant Groups

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+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. United States 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. [2020]

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

Analytical Treatment Interruption in HIV Trials: Statistical and Study Design Considerations. [2022]

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

Balancing Statistical Power and Risk in HIV Cure Clinical Trial Design. [2022]

4. England 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. [2006]

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

Acute HIV-1 infection viremia associate with rebound upon treatment interruption. [2023]

6. United States 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. [2021]

7. England pubmed.ncbi.nlm.nih.gov

A collaborative, multidisciplinary approach to HIV transmission risk mitigation during analytic treatment interruption. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Recommendations for analytical antiretroviral treatment interruptions in HIV research trials-report of a consensus meeting. [2023]

9. England 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. [2021]

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

CD4+ cell-count-guided treatment interruptions in chronic HIV-infected patients with good response to highly active antiretroviral therapy. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Analytical antiretroviral therapy interruption does not irreversibly change preinterruption levels of cellular HIV. [2020]