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Biomarkers to Predict Time to Plasma HIV RNA Rebound

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ClinicalTrials.gov Identifier: NCT03001128
Recruitment Status : Recruiting
First Posted : December 22, 2016
Last Update Posted : December 1, 2017
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment
HIV-1 Infection Drug: Antiretroviral treatment pause

Study Design

Study Type : Observational
Estimated Enrollment : 66 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Identification of Biomarkers to Predict Time to Plasma HIV RNA Rebound and Post-Treatment Viral Control During an Intensively Monitored Antiretroviral Pause (IMAP)
Actual Study Start Date : February 23, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Groups and Cohorts

Group/Cohort Intervention/treatment
Cohort A: ART initiated during chronic infection
Cohort A will include 36 participants who initiated ART during chronic infection.
Drug: Antiretroviral treatment pause
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
Antiretroviral treatment pause

Outcome Measures

Primary Outcome Measures :
  1. Time from ART discontinuation (start of MAP) to HIV RNA rebound to ≥ 1,000 copies/mL [ Time Frame: Up to 96 weeks following ART discontinuation ]
  2. Frequency of sustained post-treatment HIV control in participants treated during early and chronic infection undergoing an IMAP [ Time Frame: ≥24 weeks off ART without meeting ART re-initiation criteria ]
  3. Association between pre-IMAP CA-RNA and time to HIV rebound [ Time Frame: Up to 96 weeks following ART discontinuation ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Step 1 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.

  • 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 and/or available medical records).
  • For Cohort B, diagnosis of acute HIV infection (AHI) (as defined by the criteria listed below) and initiation of ART within 45 days after AHI diagnosis (defined as earliest date of positive HIV-1 RNA or antigen/antibody assay).

    1. Documented diagnosis during Fiebig Stages III-V. OR
    2. Enzyme or chemiluminescence immunoassays (E/CIA) IgM positive, HIV-1 RNA or p24 antigen-positive, and negative or indeterminate Western blot. OR
    3. Diagnosis during Fiebig stages I-II, but ART initiated >10 days after AHI diagnosis. Diagnosis of Fiebig stage I-II infection involves the following criteria: E/CIA negative, HIV-1 RNA or p24 antigen-positive, and negative or indeterminate Western blot.

NOTE: Candidates who were diagnosed with AHI based on this criterion ("c" above) must have had a positive HIV-1 RNA test or subsequently have had a positive Western blot.

  • 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 60 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 the 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 of <20 copies/mL obtained by the Roche TaqMan v2.0 assay or <40 copies/mL obtained by the Abbott assay, within 60 days prior to entry.
  • The following laboratory values obtained within 60 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 60 days prior to study entry or, if the HCV antibody result is positive, a negative HCV RNA result within 60 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.

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 60 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).

Step 1 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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03001128

United States, California
601 University of California, Los Angeles CARE Center CRS Recruiting
Los Angeles, California, United States, 90035
Contact: Arezou Sadighi-Akha    310-206-6414    asadighi@mednet.ucla.edu   
Principal Investigator: Raphael Landovitz, MD         
701 University of California, San Diego AntiViral Research Center CRS Recruiting
San Diego, California, United States, 92103
Contact: Jill Kunkel    619-543-8080 ext 263    jkunkel@ucsd.edu   
Principal Investigator: Constance A. Benson, MD         
801 University of California, San Francisco HIV/AIDS CRS Recruiting
San Francisco, California, United States, 94110
Contact: Jay Dwyer, RN    415-514-0550 ext 354    jdwyer@php.ucsf.edu   
Principal Investigator: Diane V. Havlir, MD         
United States, District of Columbia
Whitman Walker Health CRS (31791) Recruiting
Washington, District of Columbia, United States, 20009
Contact: Anna Wimpelberg, CCRC    202-797-3589    awimpelberg@whitman-walker.org   
Principal Investigator: W. David Hardy, MD         
United States, Illinois
2701 Northwestern University CRS Recruiting
Chicago, Illinois, United States, 60611
Contact: Baiba Berzins, MPH    312-695-5012    baiba@northwestern.edu   
Principal Investigator: Babafemi Taiwo, MBBS, MD         
United States, Massachusetts
101 Massachusetts General Hospital (MGH) CRS Recruiting
Boston, Massachusetts, United States, 02114
Contact: Teri Flynn, RN, ANP, MSN    617-724-0072    tflynn@partners.org   
Principal Investigator: Rajesh Gandhi, MD         
107 Brigham and Women's Hosp. ACTG CRS Recruiting
Boston, Massachusetts, United States, 02115
Contact: Cheryl Keenan, RN    617-732-5635    CKeenan@BWH.Harvard.edu   
Principal Investigator: Paul E. Sax, MD         
United States, North Carolina
3201 Chapel Hill CRS Recruiting
Chapel Hill, North Carolina, United States, 27516
Contact: Susan Pedersen, RN, BSN    919-966-6712    spederse@med.unc.edu   
Principal Investigator: David A. Wohl, MD         
3203 Greensboro CRS Recruiting
Greensboro, North Carolina, United States, 27401
Contact: Kim Epperson, RN    336-832-7888    kim.epperson@mosecone.com   
Principal Investigator: Cornelius Van Dam, MD         
United States, Pennsylvania
Pittsburgh CRS (1001) Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Patricia Peters    412-383-1675    pep1@pitt.edu   
Principal Investigator: Sharon Riddler, MD, MPH         
United States, Tennessee
3652 Vanderbilt Therapeutics (VT) CRS Recruiting
Nashville, Tennessee, United States, 37204
Contact: Bevery Woodward, RN, MSN    615-936-8516    beverly.o.woodward@vanderbilt.edu   
Principal Investigator: David W. Haas, MD         
Puerto Rico
5401 Puerto Rico AIDS Clinical Trials Unit CRS Recruiting
San Juan, Puerto Rico, 00931
Contact: Sylvia I. Davila Nieves, M.S.    1-787-767-9192    sylvia.davila@upr.edu   
Principal Investigator: Jorge L Santana-Bagur, MD         
Sponsors and Collaborators
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Jonathan Li, MD, MMS Brigham and Women's Hospital ACTG CRS
Study Chair: David Smith, MD, MAS University of California San Diego AVRC CRS
More Information

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT03001128     History of Changes
Other Study ID Numbers: ACTG A5345
UM1AI068636 ( U.S. NIH Grant/Contract )
First Posted: December 22, 2016    Key Record Dates
Last Update Posted: December 1, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided