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Trial record 1 of 1 for:    A5354
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Early ART to Limit Infection and Establishment of Reservoir (EARLIER)

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ClinicalTrials.gov Identifier: NCT02859558
Recruitment Status : Recruiting
First Posted : August 9, 2016
Last Update Posted : September 26, 2019
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Tracking Information
First Submitted Date  ICMJE August 4, 2016
First Posted Date  ICMJE August 9, 2016
Last Update Posted Date September 26, 2019
Actual Study Start Date  ICMJE January 2017
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2016)
Cell-associated HIV-1 DNA (CAHD) in 5 million blood-derived CD4+ T-cells assayed by qPCR [ Time Frame: 48 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02859558 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 4, 2016)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Early ART to Limit Infection and Establishment of Reservoir
Official Title  ICMJE Effect of Antiretroviral Treatment Initiated During Acute HIV-1 Infection on Measures of HIV-1 Persistence and on HIV-1-Specific Immune Responses
Brief Summary

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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1 Infection
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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
    Intervention: Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy
  • 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
    Intervention: Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy
  • 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
    Intervention: Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 4, 2016)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 or CE-marked 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Brazil,   Malawi,   Peru,   South Africa,   Thailand,   United States,   Zimbabwe
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02859558
Other Study ID Numbers  ICMJE ACTG A5354
2UM1AI068636 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party AIDS Clinical Trials Group
Study Sponsor  ICMJE AIDS Clinical Trials Group
Collaborators  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Investigators  ICMJE Not Provided
PRS Account AIDS Clinical Trials Group
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP