Observational PIC Destination Cohort

NCT05985642 | Recruiting DMC

• 2 other identifiers: ACTG A5385UM1AI068636
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

This study is being done to see if people who control HIV without antiretroviral therapy (ART) after receiving an intervention can remain off ART safely. The information collected in this study is also being used to try to understand how people control HIV without ART after receiving an intervention.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (7)

• Occurrence of an SAE or Grade ≥3 AE that is related to ATI

  The proportion of participants reporting a serious adverse event (SAE) or a grade ≥ 3 adverse event (AE) that was judged by the A5385 clinical management committee to be at least possibly related to ATI during Step 1. An AE is any unfavorable and unintended sign, symptom, or diagnosis occurring in a study participant during the conduct of the study regardless of the attribution. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation or existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or require intervention to prevent one of the outcomes listed above. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death.

  From study entry to 96 weeks

• Change in CD4 percentage from parent study (pre-ATI) to Step 1 timepoints

  Changes in CD4 percentage (CD4%) are calculated as the CD4% at the specified Step 1 timepoint minus the CD4% measured at the pre-ATI timepoint in the qualifying parent study.

  From study entry to 96 weeks

• Occurrence of new diagnoses of interest

  Occurrence of new diagnoses of interest during Step 1 and Step 2.

  From study entry through 144 weeks

• Time from ATI to sustained HIV-1 RNA ≥1000 copies/mL

  Time from ATI to sustained HIV-1 RNA ≥1000 copies/mL over a 4-week period during Step 1.

  From study entry to 96 weeks

• HIV RNA below 200 copies/mL

  The proportion of participants with HIV RNA below 200 copies/mL at 8, 12, and 24 weeks after ART restart.

  24 weeks after re-starting ART

• Change in CD4% from pre-ATI to Step 2

  Change in CD4% from pre-ATI (parent study) to Step 2 Week 12 and Step 2 Week 24 (after ART restart).

  From study entry to Step 2 week 24

• Measurements of reservoir

  Measurements of reservoir \[e.g., intact proviral DNA assay (IPDA)\] every 24 weeks during ATI, and 24 and 48 weeks after ART restart.

  From 24 weeks to 48 weeks after ART restart

Secondary Outcomes (5)

• Time from ATI to ART restart due to a viral, immune, or clinical reason

  From study entry to 96 weeks

• Time from ATI to ART restart

  From study entry to 96 weeks

• Measurement of circulating reservoir

  Every 24 weeks in Step 1 (up to 96 weeks) and Step 2 Week 24 and 48

• Plasma HIV-1 RNA at each study visit

  From study entry to 144 weeks

• Measurement of replication-competent virus

  Every 24 weeks in Step 1 (up to 96 weeks) and Step 2 Week 24 and 48

Other Outcomes (4)

• Biomarkers of systemic inflammation and immune activation

  From 24 weeks to 48 weeks after ART restart

• Anti-HIV cellular humoral and innate responses

  From 24 weeks to 48 weeks after ART restart

• Association of viral or host characteristics with time to ART restart

  From study entry to 96 weeks

Study Arms (1)

Observational PIC Destination Cohort

Step 1: Continued analytical treatment interruption (ATI) - During Step 1, PICs will be monitored for safety (including liver function, creatinine, pregnancy, and STI testing), viral, immune, neuropsychological, and socio-behavioral outcomes for up to 96 weeks of continued ATI. Step 2: ART Restart - Participants will begin Step 2 if they meet ART restart criteria or reach week 96. Participants will be monitored for safety (including liver function, creatinine, and pregnancy), immune, viral, neuropsychological, and socio-behavioral outcomes through 48 weeks after ART restart.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants who achieved prolonged viral control off ART post-intervention (post-intervention control \[PIC\]) in qualifying ACTG and non-ACTG interventional cure trials (parent studies).

You may qualify if:

• Currently or previously enrolled in a qualifying ACTG or non- ACTG parent study of curative or suppressive HIV therapy that included an ATI.
• If feasible, participants should not remain co-enrolled in their respective parent study after entering A5385.
• Achieved at least 24 weeks of HIV virus suppression (as defined by the parent study) following ATI initiation, remains off ART with \<4 consecutive weeks of HIV-1 RNA \>1000 copies/mL, CD4+ T-cell count \> 350 cells/mm3 and not experiencing symptoms of acute retroviral syndrome.
• NOTE: Participants whose participation has ended on the parent study may still qualify if they have not resumed ART, meet A5385's eligibility criteria, and have not met A5385 ART restart criteria.
• CD4+ T cell count \>350 cells/mm3 obtained within 28 days prior to study entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that is IQA certified.
• Willingness to continue ATI for up to 96 weeks or until ART restart criteria are met, and to remain in follow up for 48 weeks after ART restart.
• For participants who are able to become pregnant, negative serum or urine pregnancy test within 24 hours prior to study entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs.
• NOTE A: Participants who are able to become pregnant are individuals who have not been post-menopausal for at least 24 consecutive months, who have had menses within the preceding 24 months, and who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy, tubal ligation, or bilateral salpingectomy.
• NOTE B: Acceptable documentation of hysterectomy and bilateral oophorectomy, tubal ligation, and tubal micro-inserts: written documentation or oral communication from a clinician or clinician's staff documented in source documents (physician report/letter, operative report or other source documentation in the patient record, discharge summary, laboratory report, etc.). Participant-reported history is acceptable for documentation of menopause.
• Participants who are able to become pregnant and are engaging in sexual activity that could lead to pregnancy must agree to use one highly effective method of contraception throughout the course of the study from the list below.
• Acceptable methods of contraception include:
• Barrier method
• Contraceptive subdermal implant
• Intrauterine device or intrauterine system
• Combined estrogen and progestogen oral contraceptive

You may not qualify if:

• Intercurrent illness, new medical diagnosis, laboratory abnormality, sign, or symptom that, in the opinion of the site investigator, would place participant at higher risk of morbidity during continued ATI.
• Medical or psychiatric condition (including pregnancy or breastfeeding) that, in the opinion of the site investigator, would place the participant at higher risk of morbidity or would interfere with adherence to study requirements.
• NOTE: Site investigators should exercise caution in invoking these criteria and instead aim to support potential participants who are interested and otherwise eligible to participate in the study.
• Medical or psychiatric condition that, in the opinion of the site investigator, would place the participant at higher risk of morbidity or would interfere with adherence to study requirements.
• NOTE: Site investigators should exercise caution in invoking these criteria and instead aim to support potential participants who are interested and otherwise eligible to participate in the study.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (4)

University of California, San Francisco HIV/AIDS CRS (801)

San Francisco, California, 94110, United States

RECRUITING

Washington University Therapeutics (WT) CRS (2101)

St Louis, Missouri, 63110, United States

RECRUITING

Weill Cornell Upton CRS (7803)

New York, New York, 10065, United States

RECRUITING

Case CRS (2501)

Cleveland, Ohio, 44106, United States

RECRUITING

Study Officials

• Katharine Bar, MD

  Penn Therapeutics Clinical Research Site

  STUDY CHAIR

Central Study Contacts

ACTG ClinicalTrials.gov Coordinator

CONTACT

(301)628-3348; ACTGCT.gov@dlhcorp.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: August 14, 2023
• Study Start: March 19, 2024
• Primary Completion (Estimated): July 3, 2029
• Study Completion (Estimated): September 3, 2029
• Last Updated: December 13, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Acknowledgement before receiving the data.

Locations

US (4)