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Early ART to Limit Infection and Establishment of Reservoir (EARLIER)

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by AIDS Clinical Trials Group
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT02859558
First received: August 4, 2016
Last updated: May 1, 2017
Last verified: May 2017
  Purpose

The study is being done to:

  • start ART early in those recently or acutely infected with HIV-1
  • see how starting ART as soon as the infection is found affects the amount of HIV-1 in blood and how well the body fights the HIV-1 infection
  • look at the amount of HIV-1 DNA (genetic material for HIV-1) seen in CD4+ T-cells (infection-fighting cells in blood) after 48 weeks of ART
  • see how early treatment for HIV affects the numbers of HIV-1 infection fighting cells (CD4+ and CD8+ T-cells) in blood

Condition Intervention Phase
HIV-1 Infection Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Effect of Antiretroviral Treatment Initiated During Acute HIV-1 Infection on Measures of HIV-1 Persistence and on HIV-1-Specific Immune Responses

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Cell-associated HIV-1 DNA (CAHD) in 5 million blood-derived CD4+ T-cells assayed by qPCR [ Time Frame: 48 weeks ]

Secondary Outcome Measures:
  • HIV-1-specific CD4+ and CD8+ T-cell responses by flow cytometry [ Time Frame: 48 weeks ]
    Evaluate HIV-1-specific CD4+ and CD8+ T-cell responses (magnitude and distribution) to nef/tat/rev/vpr/vpu, gag, pol and env by flow cytometry, and the quality of T-cell responses (frequency and type of polyfunctional responses) prior to ART initiation and while HIV-1 RNA is suppressed on ART

  • Cell-associated HIV-1 RNA in 5 million blood-derived CD4+ T-cells assayed by qPCR [ Time Frame: 48 weeks ]
    Assess cell-associated HIV-1 RNA per 5 million CD4+ T-cells assayed by qPCR prior to ART initiation and while HIV-1 RNA is suppressed on ART

  • Cell-associated HIV-1 RNA/DNA ratio in 5 million blood-derived CD4+ T-cells assayed by qPCR [ Time Frame: 48 weeks ]
    Assess cell-associated HIV-1 RNA/DNA ratio in participants with detectable cell-associated HIV-1 DNA prior to ART initiation and while HIV-1 RNA is suppressed on ART


Estimated Enrollment: 150
Actual Study Start Date: January 2017
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Fiebig I II
Participants enrolled during Fiebig stages I-II will receive antiretroviral therapy consisting of either one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg (also known as EVG/COBI/FTC/TAF or Genvoya) by mouth daily or another medically-appropriate antiretroviral therapy
Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy
Participants will receive one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg by mouth daily with food.
Other Name: Single-tablet regimen EVG/COBI/FTC/TAF or Genvoya
Experimental: Arm 2: Fiebig III IV
Participants enrolled during Fiebig stages III-IV will receive antiretroviral therapy consisting of either one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg (also known as EVG/COBI/FTC/TAF or Genvoya) by mouth daily or another medically-appropriate antiretroviral therapy
Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy
Participants will receive one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg by mouth daily with food.
Other Name: Single-tablet regimen EVG/COBI/FTC/TAF or Genvoya
Experimental: Arm 3: Fiebig V
Participants enrolled during Fiebig stages V will receive antiretroviral therapy consisting of either one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg (also known as EVG/COBI/FTC/TAF or Genvoya) by mouth daily or another medically-appropriate antiretroviral therapy
Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy
Participants will receive one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg by mouth daily with food.
Other Name: Single-tablet regimen EVG/COBI/FTC/TAF or Genvoya

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Appropriate documentation from medical records of diagnosis of acute HIV-1 infection (AHI) within 7 days prior to enrollment, that includes one of the following:

    1. A detectable HIV-1 RNA within 28 days prior to study entry AND a non-reactive HIV-1 antibody within 7 days prior to entry OR
    2. A detectable HIV-1 RNA or a reactive HIV-1 antibody within 28 days prior to study entry AND a negative/indeterminate WB or negative/indeterminate Geenius HIV-1/HIV-2 Supplemental Assay within 7 days prior to entry OR
    3. A documented non-reactive HIV-1 antibody or negative HIV-1 RNA within 90 days prior to study entry AND a documented reactive HIV-1 antibody or positive WB that is negative for p31 band or a positive Geenius HIV-1/HIV-2 Supplemental Assay that is negative for p31 band within 7 days prior to entry OR
    4. ARCHITECT or GSCOMBO S/CO ≥10 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry OR
    5. ARCHITECT or GSCOMBO S/CO ≥1 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry AND a known prior S/CO <0.5 within 90 days prior to entry OR
    6. ARCHITECT or GSCOMBO S/CO >0.5 but <10 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry AND detectable HIV-1 RNA within 7 days prior to entry

NOTE A: HIV-1 RNA result must be reported from an FDA-approved assay.

NOTE B: Since characterization of Fiebig stage using samples at the time of ART initiation will be performed with results known within 12 weeks based on standardized, centralized testing, an estimated Fiebig group at enrollment based on inclusion criteria as shown in the table above will provide additional real-time monitoring for accruals into each study group. The protocol team will notify the sites if some criteria may no longer be used because accrual is completed in certain Fiebig groups.

NOTE C: Specimens for the testing specified above may be collected on the day of study entry provided the testing result is available prior to enrollment.

  • Ability and willingness of candidate to provide written informed consent.
  • Ability and willingness to initiate ART at enrollment.
  • Ability and willingness to participate in scheduled study visits for up to 72 weeks.
  • Female candidates of reproductive potential who are not pregnant at the time of enrollment and who will receive the study-provided EVG/COBI/FTC/TAF and must agree not to participate in the conception process (ie, active attempt to become pregnant, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female candidate must agree to use at least one reliable form of contraceptive while receiving study-provided treatment.

Female candidates are considered to be of reproductive potential if any of the following conditions apply:

  • Candidate has experienced menarche.
  • Candidate has not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
  • Candidate has not experienced menopause, defined as lack of menstruation within the preceding 12 months.

Acceptable contraceptive methods include:

  • Condoms (male or female) with or without a spermicidal agent
  • Diaphragm or cervical cap with spermicide
  • Intrauterine device
  • Hormonal contraceptive

Female candidates who are not of reproductive potential or whose male partner(s) has documented azoospermia are not required to use contraceptives. Any statement of self-reported sterility or that of her partner must be entered in the source documents.

NOTE: Acceptable documentation of lack of reproductive potential is oral or written documentation from the individual.

Female candidates who are prescribed a non-study-provided ARV regimen should discuss the safety of that regimen during conception and pregnancy with the prescribing physician. Such individuals should follow medical guidance regarding any potential need for contraception while using the non-study-provided ARV regimen.

NOTE: Pregnant and breastfeeding women may enroll in the study provided that they meet the eligibility requirements and have access to non-study-provided ARV regimens.

Exclusion Criteria:

  • Positive HIV-1 antibody test ≥90 days prior to study entry.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Any acute, chronic, or recent and clinically significant medical condition that, in the opinion of the site investigator, would interfere with adherence to study requirements or jeopardize the safety or rights of the participant.
  • Receipt of an investigational study agent within 28 days prior to enrollment
  • Chronic or recurrent use of medications that modify host immune response, eg, oral or parenteral steroids, cancer chemotherapy.
  • AHI diagnosis within 60 days after receiving any investigational ARV or HIV-1 vaccine or immune prophylaxis for HIV-1 infection.
  • Use of ARVs for pre- or post-exposure prophylaxis within 60 days prior to the diagnosis of AHI.

NOTE: The rationale for this exclusion is to minimize the impact of therapy on the primary endpoint.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02859558

Locations
United States, Alabama
31788 Alabama CRS Recruiting
Birmingham, Alabama, United States, 35294
Contact: Karen G Savage, BSN    205-996-2373      
Principal Investigator: Edgar Overton, MD         
United States, California
UCLA CARE Center CRS (601) Recruiting
Los Angeles, California, United States, 90095
Contact: Arezou Akha    310-557-3798    asadighi@mednet.ucla.edudu   
Principal Investigator: Raphael Landovitz, MD         
Ucsd, Avrc Crs (701) Recruiting
San Diego, California, United States, 92103
Contact: Jill Kunkel, RN    619-543-8080    jkunkel@ucsd.edu   
Principal Investigator: Constance Benson, MD         
Harbor-UCLA Med. Ctr. CRS (603) Recruiting
Torrance, California, United States, 90502
Contact: Mario Guerrero    310-222-3848    mguerrero@labiomed.org   
Principal Investigator: Eric S. Daar, MD         
United States, District of Columbia
Whitman Walker Health CRS (31791) Recruiting
Washington, D.C., 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, Georgia
The Ponce de Leon Center CRS (5802) Recruiting
Atlanta, Georgia, United States, 30308
Contact: Ericka Patrick    404-616-6313    erpatri@emory.edu   
Principal Investigator: Carlos del Rio, MD         
United States, Illinois
Northwestern University CRS (2701) Recruiting
Chicago, Illinois, United States, 60611
Contact: Baiba Berzins, MPH    312-695-5012    baiba@northwestern.edu   
Principal Investigator: Babafemi Taiwo, MBBS, MD         
Rush Univ. Med. Ctr. ACTG CRS (2702) Recruiting
Chicago, Illinois, United States, 60612
Contact: Janice Fritsche, M.S.    312-942-4810    jfrits@rush.edu   
Principal Investigator: Beverly E Sha, MD         
United States, Massachusetts
Massachusetts General Hospital ACTG CRS (101) Recruiting
Boston, Massachusetts, United States, 02114
Contact: Teri Flynn, RN, MSN, ANP    1-617-724-0072    tflynn@partners.org   
Principal Investigator: Rajesh T. Gandhi, MD         
Brigham and Women's Hosp. ACTG CRS (107) Recruiting
Boston, Massachusetts, United States, 02115
Contact: Cheryl Keenan, RN, BSN    617-732-5635    ckeenan2@partners.org   
Principal Investigator: Paul E. Sax, MD         
United States, Missouri
Washington University CRS (2101) Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Michael Klebert, RN, PhD, CANP    314-454-0058    mklebert@wustl.edu   
Principal Investigator: David Clifford, MD         
United States, North Carolina
Greensboro CRS (3203) Recruiting
Greensboro, North Carolina, United States, 27401
Contact: Kim Epperson, RN, BSN, CCRC    336-832-7888    kim.epperson@mosecone.com   
Principal Investigator: Cornelius Van Dam, MD         
United States, Ohio
The Ohio State Univ. AIDS CRS (2301) Recruiting
Columbus, Ohio, United States, 43210
Contact: Kathy Watson, RN    614-293-5856    kathy.watson@osumc.edu   
Principal Investigator: Susan Koletar, MD         
United States, Rhode Island
The Miriam Hosp. ACTG CRS (2951) Recruiting
Providence, Rhode Island, United States, 02906
Contact: Pamela Poethke, RN    401-793-4971    ppoethke@lifespan.org   
Principal Investigator: Karen T. Tashim, MD         
United States, Texas
31473 Houston AIDS Research Team (HART) CRS Recruiting
Houston, Texas, United States, 77030
Contact: Maria Martinez    713-500-6718      
Principal Investigator: Roberto C. Arduino, MD         
United States, Washington
University of Washington AIDS CRS (1401) Recruiting
Seattle, Washington, United States, 98104
Contact: Christine Jonsson    206-744-8886    cjonsson@uw.edu   
Principal Investigator: Ann Collier, MD         
Sponsors and Collaborators
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT02859558     History of Changes
Other Study ID Numbers: ACTG A5354
2UM1AI068636 ( U.S. NIH Grant/Contract )
Study First Received: August 4, 2016
Last Updated: May 1, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Emtricitabine
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Cobicistat
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 26, 2017