Biomarkers to Predict Time to Plasma HIV RNA Rebound

NCT ID: NCT03001128

Last Updated: 2024-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

61 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-02-23

Study Completion Date

2021-01-29

Brief Summary

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The purpose of this study is to collect information about what happens when people pause, or temporarily stop taking, ART, and to collect blood samples from these people at frequent intervals. We will also study the safety of pausing ART under close observation.

Detailed Description

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Conditions

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HIV-1 Infection

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort A: ART initiated during chronic infection

Cohort A will include 36 participants who initiated ART during chronic infection.

Antiretroviral treatment pause

Intervention Type DRUG

Antiretroviral treatment pause

Cohort B: ART initiated during acute or early infection

Cohort B will include 30 participants who initiated ART during acute/early HIV infection.

Antiretroviral treatment pause

Intervention Type DRUG

Antiretroviral treatment pause

Interventions

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Antiretroviral treatment pause

Antiretroviral treatment pause

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.

NOTE: The term "licensed" refers to a US FDA-approved kit, which is required for all IND studies, or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally.

* Plasma HIV-1 RNA \>1000 copies/mL by any assay obtained prior to initiating ART. NOTE: Documentation or candidate recall is acceptable.
* For Cohort A participants, ART initiated during chronic infection (e.g., more than 6 months after estimated date of infection, or as determined by site investigator, study team, or available medical records).
* For Cohort B, diagnosis of acute HIV infection (AHI) as defined by the criteria listed below.

Fiebig Staging Criteria (must be source documented):

* Fiebig I-II: E/CIA negative, HIV-1 RNA or p24 antigen positive, and negative or indeterminate Western blot, if performed
* Fiebig III-IV: Reactive HIV-1 antibody and negative or indeterminate results on the Western blot or Geenius HIV-1/HIV-2
* Fiebig V: Reactive HIV-1 antibody and positive Western blot or Geenius HIV-1/HIV-2 without p31 band NOTE A: ART must have been initiated more than 10 days after Fiebig I-II diagnosis and less than 90 days after Fiebig V diagnosis to qualify for Cohort B. NOTE B: Candidates who were diagnosed with Fiebig I-II AHI must have had a positive HIV-1 RNA test or subsequently have had a positive Western blot if no positive HIV-1 RNA test was available.

* Receiving continuous ART for at least 2 years and on any NNRTI-, PI-, or INSTI-containing regimen.

NOTE A: ART interruptions of up to 7 days and at least 90 days prior to entry are acceptable.

NOTE B: Within- and between-class changes in ART within the previous 2 years are acceptable.

* For candidates whose ART includes an NNRTI, willingness and ability to change to a PI- or INSTI-containing regimen for at least 4 weeks prior to ART interruption and the local availability of such a regimen.
* Nadir CD4+ cell count ≥200 cells/mm3.

NOTE: Candidate recall or documentation is acceptable.

* CD4+ cell count ≥500 cells/mm3 obtained within 90 days prior to study entry in a US laboratory that has is compliant with Clinical Laboratory Improvement Amendments (CLIA) or its equivalent or in any network approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance (EQA) programs.
* One documented plasma HIV-1 RNA that is below the limit of detection of an FDA-approved assays (limit of detection: 75, 50, 40, or 20 copies/mL) between 12 and 24 months prior to the screening HIV-1 RNA and one documented HIV-1 RNA that is below the limit of detection of the FDA-approved assays (limit of detection: 75, 50, 40, or 20 copies/mL) collected fewer than 12 months prior to the screening HIV-1 RNA.
* Plasma HIV-1 RNA level below the limit of assay quantification within 90 days prior to entry.
* The following laboratory values obtained within 90 days prior to entry by any US laboratory that is compliant with CLIA or its equivalent or in any network approved non-US laboratory that operates in accordance with GCLP and participates in appropriate EQA programs.

Absolute neutrophil count (ANC) ≥750 cells/mm3 Hemoglobin ≥11.0 g/dL for men and ≥10.0 g/dL for women Platelet count ≥100,000/mm3 Creatinine ≤1.5 mg/dL Aspartate aminotransferase (AST) (SGOT) ≤1.5x upper limit of normal (ULN) Alanine aminotransferase (ALT) (SGPT) ≤1.5x ULN

* HCV antibody negative result obtained within 90 days prior to study entry or, if the HCV antibody result is positive, a negative HCV RNA result within 90 days prior to study entry and no positive HCV RNA result within 24 weeks prior to entry.
* Ability and willingness of participant to provide informed consent.
* Willingness to have blood samples collected and stored indefinitely and used for HIV-related research purposes.
* For females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or bilateral salpingectomy), a negative serum or urine pregnancy test within 48 hours prior to study entry by any clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care CLIA-waived test, or at any network approved non-US laboratory or clinic that operates in accordance with Good Clinical Laboratory Practices and participates in appropriate external quality assurance programs.

NOTE: Acceptable documentation of hysterectomy and bilateral oophorectomy, bilateral salpingectomy, tubal micro-inserts, partner who has undergone vasectomy, and menopause is participant-reported history.

* All participants must agree to use barrier protection (e.g., condoms, dental dams) for all sexual activity throughout the entire course of the study to prevent HIV transmission.
* All participants must agree not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, or in vitro fertilization). If participating in sexual activity that could lead to pregnancy, the participant/partner must use at least two reliable forms of contraceptives (e.g., condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an IUD; hormone-based contraception), with at least one being a barrier method, during the study.
* Site investigator anticipates that a fully active alternative ART regimen could be constructed and would be available in the event of virologic failure on the participant's current ART regimen.
* Absence of either active hepatitis B virus (HBV) infection, indicated by a negative hepatitis B surface antigen (HBsAg) or HBV viral load assays within 90 days prior to entry or known chronic hepatitis B infection based on a previously positive HBV DNA or positive HBsAg without a subsequent positive hepatitis B surface antibody (HBsAb).

Exclusion Criteria

* Any plasma HIV-1 RNA at or above the limit of detection of the FDA-approved assays (limit of detection: 75, 50, 40, or 20 copies/mL) within 24 months prior to entry.

NOTE: A single unconfirmed "blip" (i.e., plasma HIV-1 RNA over limit of detection but \<200 copies/mL) is allowed if preceded and followed by values below the limit of detection and if the blip occurred more than 6 months prior to study entry.

* Currently breastfeeding or plans on breastfeeding during the course of the study or is pregnant.
* Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
* Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 60 days prior to entry.
* Any history of an AIDS-defining illness using the current list on the U.S. Centers for Disease Control and Prevention (CDC)'s website.
* Receipt of any study-defined prohibited medications within 6 months prior to entry.
* Prior history of difficulty establishing venous access or current contraindication for leukapheresis, in the opinion of the site investigator and based on assessments.
* Receipt of any vaccination within 1 week prior to entry.

NOTE: The entry visit must be scheduled to ensure that 1 week has elapsed after any vaccination.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jonathan Li, MD, MMS

Role: STUDY_CHAIR

Brigham and Women's Hospital ACTG CRS

David Smith, MD, MAS

Role: STUDY_CHAIR

University of California San Diego AVRC CRS

Locations

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601 University of California, Los Angeles CARE Center CRS

Los Angeles, California, United States

Site Status

701 University of California, San Diego AntiViral Research Center CRS

San Diego, California, United States

Site Status

801 University of California, San Francisco HIV/AIDS CRS

San Francisco, California, United States

Site Status

University of Colorado Hospital CRS (6101)

Aurora, Colorado, United States

Site Status

Whitman Walker Health CRS (31791)

Washington D.C., District of Columbia, United States

Site Status

2701 Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS (2702)

Chicago, Illinois, United States

Site Status

101 Massachusetts General Hospital (MGH) CRS

Boston, Massachusetts, United States

Site Status

107 Brigham and Women's Hosp. ACTG CRS

Boston, Massachusetts, United States

Site Status

Washington U CRS (2101)

St Louis, Missouri, United States

Site Status

University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

Rochester, New York, United States

Site Status

3201 Chapel Hill CRS

Chapel Hill, North Carolina, United States

Site Status

3203 Greensboro CRS

Greensboro, North Carolina, United States

Site Status

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, United States

Site Status

3652 Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, United States

Site Status

31443 Trinity Health and Wellness Center CRS

Dallas, Texas, United States

Site Status

5401 Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, PR, Puerto Rico

Site Status

31802 Thai Red Cross AIDS Research Centre (TRC-ARC) CRS

Bangkok, Patumwan, Thailand

Site Status

Countries

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United States Puerto Rico Thailand

References

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Gianella S, Yu T, Wang R, Ignacio C, Schanz M, Kouyos RD, Caballero G, Gaitan NC, Rawlings S, Kuster H, Metzner KJ, Gandhi RT, Li JZ, Gunthard HF, Smith DM, Chaillon A. Viral and Immune Risk Factors of HIV Rebound After Interruption of Antiretroviral Therapy. J Infect Dis. 2025 Jun 2;231(5):1221-1229. doi: 10.1093/infdis/jiae585.

Reference Type DERIVED
PMID: 39661441 (View on PubMed)

Li JZ, Melberg M, Kittilson A, Abdel-Mohsen M, Li Y, Aga E, Bosch RJ, Wonderlich ER, Kinslow J, Giron LB, Di Germanio C, Pilkinton M, MacLaren L, Keefer M, Fox L, Barr L, Acosta E, Ananworanich J, Coombs R, Mellors J, Deeks S, Gandhi RT, Busch M, Landay A, Macatangay B, Smith DM; AIDS Clinical Trials Group A5345 Study Team. Predictors of HIV rebound differ by timing of antiretroviral therapy initiation. JCI Insight. 2024 Feb 8;9(3):e173864. doi: 10.1172/jci.insight.173864.

Reference Type DERIVED
PMID: 38329130 (View on PubMed)

Dube K, Eskaf S, Barr L, Palm D, Hogg E, Simoni JM, Sugarman J, Brown B, Sauceda JA, Henley L, Deeks S, Fox L, Gandhi RT, Smith D, Li JZ. Participant Perspectives and Experiences Following an Intensively Monitored Antiretroviral Pause in the United States: Results from the AIDS Clinical Trials Group A5345 Biomarker Study. AIDS Res Hum Retroviruses. 2022 Jun;38(6):510-517. doi: 10.1089/AID.2021.0170. Epub 2022 Apr 21.

Reference Type DERIVED
PMID: 35323030 (View on PubMed)

Diepstra KL, Barr L, Palm D, Hogg E, Mollan KR, Henley L, Stover AM, Simoni JM, Sugarman J, Brown B, Sauceda JA, Deeks S, Fox L, Gandhi RT, Smith D, Li JZ, Dube K. Participant Perspectives and Experiences Entering an Intensively Monitored Antiretroviral Pause: Results from the AIDS Clinical Trials Group A5345 Biomarker Study. AIDS Res Hum Retroviruses. 2021 Jun;37(6):489-501. doi: 10.1089/AID.2020.0222. Epub 2021 Feb 16.

Reference Type DERIVED
PMID: 33472545 (View on PubMed)

Other Identifiers

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UM1AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5345

Identifier Type: -

Identifier Source: org_study_id