Observational PIC Destination Cohort

An Observational Post-Intervention Control Destination Cohort

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.

Study Overview

• Status: Recruiting
• Conditions: HIV-1-infection

Detailed Description

This study is a two-step non-interventional study for participants who achieved prolonged viral control off ART, post-intervention (post-intervention control [PIC]) in qualifying AIDS Clinical Trials Group (ACTG) and non-ACTG interventional cure trials (parent studies).

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: ACTG ClinicalTrials.gov Coordinator; Phone Number: (301)628-3348; Email: ACTGCT.gov@dlhcorp.com

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • Recruiting
      • University of California, San Francisco HIV/AIDS CRS (801)
      • Contact: Jay Dwyer, RN, ACRN, BA; Phone Number: 353 415-535-9495; Email: jay.dwyer@ucsf.edu
      • Contact: Annie Luetkemeyer, MD
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University Therapeutics (WT) CRS (2101)
      • Contact: Michael Klebert, RN, PhD; Phone Number: 314-454-0058; Email: mklebert@wustl.edu
      • Contact: Rachel Presti, MD, PhD
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Upton CRS (7803)
      • Contact: Jonathan Berardi, MS, APRN, FNP-C; Phone Number: (212) 746-4166; Email: jlb4002@med.cornell.edu
      • Contact: Phone Number: 212-746-7864
      • Contact: Marshall J. Glesby, MD
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Case CRS (2501)
      • Contact: Jeffrey Jacobson, MD
      • Contact: Julie Pasternak, BSN; Phone Number: 216-844-2738; Email: pasternak.julie@clevelandactu.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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).

Description

Step 1 Inclusion Criteria:

• 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
• Injectable progestogen
• Contraceptive vaginal ring
• Percutaneous contraceptive patches

• Male partner sterilization with documentation of azoospermia prior to the female participant's entry into the study, and this male is the sole partner for that participant.

  • Willingness to use barrier protection (male or female) during sexual activity with all partners not on effective pre-exposure prophylaxis (PrEP) throughout Step 1 ATI and until viral re-suppression in Step 2.

NOTE: Effective PrEP includes ART treatment for partners living with HIV infection.

• Ability and willingness of participant to provide informed consent.

Step 2 Inclusion Criteria:

• Met A5385 ART restart criteria in Step 1.
• Willingness to use barrier protection (male or female) during sexual activity with all partners not on effective PrEP until viral re-suppression.

NOTE: Effective PrEP includes ART treatment for partners living with HIV infection.

Step 1 Exclusion Criteria:

• 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.

Step 2 Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from ATI to ART restart due to a viral, immune, or clinical reason	Time from ATI to ART restart due to a viral reason (plasma HIV-1 RNA ≥1000 copies/mL for ≥4 consecutive weeks without at least a 0.2 log10 decline from the previous week), and immune reason (confirmed CD4+ T cell count <350), or a clinical reason (e.g., acute retroviral syndrome).	From study entry to 96 weeks
Time from ATI to ART restart	Time from ATI to ART restart, for any reason.	From study entry to 96 weeks
Measurement of circulating reservoir	Cell-associated HIV-1 DNA and HIV-1 RNA measured in CD4+ T cells.	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	Plasma HIV-1 RNA (copies/mL) at each study visit measured by clinical assay, or if unquantifiable by standard clinical assay (e.g., below the limit of quantification), single copy assay.	From study entry to 144 weeks
Measurement of replication-competent virus	Replication-competent virus, measured by the QVOA assay (or appropriate reservoir assay at time of testing).	Every 24 weeks in Step 1 (up to 96 weeks) and Step 2 Week 24 and 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of viral or host characteristics with time to ART restart	Viral or host characteristics, including, but not limited to, laboratory measures (e.g., viral, inflammatory, reservoir, immune measures), host genetics (e.g., CCR5 heterogeneity, HLA type), or host demographics (e.g., gender, biologic sex, age) for association with time to meeting HIV-1 related, or any, ART restart criteria.	From study entry to 96 weeks
Virus properties and immune responses surrounding time of viral rebound	Properties of rebound virus, including genotype and phenotype by relevant assays, and immune response surrounding time of viral rebound.	From study entry to 96 weeks
Biomarkers of systemic inflammation and immune activation	Measurements of plasma soluble biomarkers of systemic inflammation and immune activation every 24 weeks during ATI and at 24 and 48 weeks after ART restart.	From 24 weeks to 48 weeks after ART restart
Anti-HIV cellular humoral and innate responses	Anti-HIV cellular humoral and innate responses every 24 weeks during ATI and at 24 and 48 weeks after ART restart.	From 24 weeks to 48 weeks after ART restart

Collaborators and Investigators

• Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Katharine Bar, MD, Penn Therapeutics Clinical Research Site

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2024
• Primary Completion (Estimated): July 3, 2029
• Study Completion (Estimated): September 3, 2029

Study Registration Dates

• First Submitted: June 28, 2023
• First Submitted That Met QC Criteria: August 8, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Estimated): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: ACTG A5385; UM1AI068636 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie results in the publication, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No