Biomarkers to Predict Time to Plasma HIV RNA Rebound

NCT03001128 | Completed DMC

• 2 other identifiers: ACTG A5345UM1AI068636
• Study Type: observational
• Target: 61
• Locations: 3 countries
• Sites: 18

Brief Summary

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (3)

• Time from ART discontinuation to HIV RNA rebound

  Time from ART discontinuation (start of MAP) to HIV RNA rebound to ≥ 1,000 copies/mL

  Up to 96 weeks following ART discontinuation

• Frequency of sustained post-treatment HIV control

  Frequency of sustained post-treatment HIV control in participants treated during early and chronic infection undergoing an IMAP

  ≥24 weeks off ART without meeting ART re-initiation criteria

• Association between pre-IMAP CA-RNA and time to HIV rebound

  Association between pre-IMAP CA-RNA and time to HIV rebound

  Up to 96 weeks following ART discontinuation

Study Arms (2)

Cohort A: ART initiated during chronic infection

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

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.

Drug: Antiretroviral treatment pause

Interventions

Antiretroviral treatment pause DRUG

Antiretroviral treatment pause

Cohort A: ART initiated during chronic infection; Cohort B: ART initiated during acute or early infection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV-infected men and women ≥18 to ≤70 years of age, maintained on suppressive ART for a minimum of 2 years with CD4+ count ≥500 cells/mm3 and nadir CD4+ count ≥200 cells/mm3.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (18)

601 University of California, Los Angeles CARE Center CRS

Los Angeles, California, 90035, United States

Location

701 University of California, San Diego AntiViral Research Center CRS

San Diego, California, 92103, United States

Location

801 University of California, San Francisco HIV/AIDS CRS

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Whitman Walker Health CRS (31791)

Washington D.C., District of Columbia, 20009, United States

Location

2701 Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

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

Chicago, Illinois, 60612, United States

Location

101 Massachusetts General Hospital (MGH) CRS

Boston, Massachusetts, 02114, United States

Location

107 Brigham and Women's Hosp. ACTG CRS

Boston, Massachusetts, 02115, United States

Location

Washington U CRS (2101)

St Louis, Missouri, 63110, United States

Location

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

Rochester, New York, 14642, United States

Location

3201 Chapel Hill CRS

Chapel Hill, North Carolina, 27516, United States

Location

3203 Greensboro CRS

Greensboro, North Carolina, 27401, United States

Location

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

3652 Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

31443 Trinity Health and Wellness Center CRS

Dallas, Texas, 75208, United States

Location

5401 Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, PR, 00931, Puerto Rico

Location

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

Bangkok, Patumwan, 10330, Thailand

Location

Related Publications (4)

• 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.

  PMID: 39661441 DERIVED

• 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.

  PMID: 38329130 DERIVED

• 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.

  PMID: 35323030 DERIVED

• 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.

  PMID: 33472545 DERIVED

Study Officials

• Jonathan Li, MD, MMS

  Brigham and Women's Hospital ACTG CRS

  STUDY CHAIR

• David Smith, MD, MAS

  University of California San Diego AVRC CRS

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: December 22, 2016
• Study Start: February 23, 2017
• Primary Completion: January 29, 2021
• Study Completion: January 29, 2021
• Last Updated: December 13, 2024

Record last verified: 2024-12

Locations

US (16); PR (1); TH (1)