Early ART to Limit Infection and Establishment of Reservoir
NCT ID: NCT02859558
Last Updated: 2025-08-29
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
195 participants
INTERVENTIONAL
2017-01-24
2025-04-16
Brief Summary
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* Start antiretroviral therapy (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
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Detailed Description
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Participants were followed for up to 216 weeks (72 weeks on Step 1 and 144 weeks on Step 2). Evaluations at weeks 2 and 8 on Step 1 were performed via telephone.
The Fiebig stage-classification system was used to characterize the progression from HIV-1 exposure to HIV-1 seroconversion at the time of ART initiation. In this study, the five Fiebig stages of interest were simplified into three study groups as described below (based on HIV-1 antibody diagnostic profile at time of ART initiation).
The primary analysis was based on Step 1. Step 2 was added to the study for long term follow-up. The rationale for the extended follow-up period was to expand the number of available participants for future therapeutic and cure studies without the burden of frequent visits and the cost of study-provided laboratory testing.
Group 1: Fiebig I/II (non-reactive HIV-1 antibody)
Group 2: Fiebig III/IV (reactive HIV-1 antibody and negative or indeterminate results on the Western Blot (WB) or Geenius HIV-1/HIV-2)
Group 3: Fiebig V (reactive HIV-1 antibody and positive WB or Geenius HIV-1/HIV-2 without p31 band)
Although participants in Fiebig VI (positive WB or Geenius HIV-1/HIV-2 with p31 band) were not specifically targeted for enrollment in this study, it was possible that a small number of participants would be determined to be in Fiebig VI (positive Western blot or Geenius HIV-1/HIV-2 with p31 band) based on analysis of the entry samples. Participants who were determined to be in Fiebig VI were followed on the study for no more than 24 weeks on Step 1, allowing ample time for them to pursue alternative sources for ART. Enrolled participants without HIV or in Fiebig VI were replaced.
The study-provided regimen was single tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Other non-study-provided antiretroviral (ARV) regimens were also allowed for participants who were pregnant, breastfeeding, or unable/unwilling to take EVG/COBI/FTC/TAF or BIC/FTC/TAF, or for participants whose local health care/primary care provider preferred starting a different initial ARV regimen.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm 1: Fiebig I/II
Participants enrolled during Fiebig stages I or II (non-reactive HIV-1 antibody).
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy
Participants received one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg by mouth daily with food or one tablet of bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg by mouth daily with or without food. Other non-study-provided ARV regimens were allowed for participants who were pregnant, breastfeeding, or unable/unwilling to take EVG/COBI/FTC/TAF or BIC/FTC/TAF, or for participants whose local health care/primary care provider preferred starting a different initial ARV regimen.
Arm 2: Fiebig III/IV
Participants enrolled during Fiebig stages III or IV (reactive HIV-1 antibody and negative or indeterminate results on the Western blot or Geenius HIV-1/HIV-2).
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy
Participants received one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg by mouth daily with food or one tablet of bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg by mouth daily with or without food. Other non-study-provided ARV regimens were allowed for participants who were pregnant, breastfeeding, or unable/unwilling to take EVG/COBI/FTC/TAF or BIC/FTC/TAF, or for participants whose local health care/primary care provider preferred starting a different initial ARV regimen.
Arm 3: Fiebig V
Participants enrolled during Fiebig stage V (reactive HIV-1 antibody and positive Western blot or Geenius HIV-1/HIV-2 without p31 band).
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy
Participants received one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg by mouth daily with food or one tablet of bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg by mouth daily with or without food. Other non-study-provided ARV regimens were allowed for participants who were pregnant, breastfeeding, or unable/unwilling to take EVG/COBI/FTC/TAF or BIC/FTC/TAF, or for participants whose local health care/primary care provider preferred starting a different initial ARV regimen.
Interventions
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elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy
Participants received one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg by mouth daily with food or one tablet of bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg by mouth daily with or without food. Other non-study-provided ARV regimens were allowed for participants who were pregnant, breastfeeding, or unable/unwilling to take EVG/COBI/FTC/TAF or BIC/FTC/TAF, or for participants whose local health care/primary care provider preferred starting a different initial ARV regimen.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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.
* 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
* 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.
18 Years
ALL
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
NETWORK
Responsible Party
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Locations
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31788 Alabama CRS
Birmingham, Alabama, United States
Ucsd, Avrc Crs (701)
San Diego, California, United States
Harbor-UCLA Med. Ctr. CRS (603)
Torrance, California, United States
Whitman Walker Health CRS (31791)
Washington D.C., District of Columbia, United States
The Ponce de Leon Center CRS (5802)
Atlanta, Georgia, United States
Northwestern University CRS (2701)
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS (2702)
Chicago, Illinois, United States
Massachusetts General Hospital ACTG CRS (101)
Boston, Massachusetts, United States
Brigham and Women's Hosp. ACTG CRS (107)
Boston, Massachusetts, United States
Washington University CRS (2101)
St Louis, Missouri, United States
31786 New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, United States
7804 Weill Cornell Chelsea CRS
New York, New York, United States
Columbia Physicians and Surgeons CRS (30329)
New York, New York, United States
3201 Chapel Hill CRS
Chapel Hill, North Carolina, United States
Greensboro CRS (3203)
Greensboro, North Carolina, United States
Univ. of Cincinnati CRS (2401)
Cincinnati, Ohio, United States
The Ohio State Univ. AIDS CRS (2301)
Columbus, Ohio, United States
6201 Penn Therapeutics CRS
Philadelphia, Pennsylvania, United States
Pittsburgh CRS (1001)
Pittsburgh, Pennsylvania, United States
The Miriam Hosp. ACTG CRS (2951)
Providence, Rhode Island, United States
31443 Trinity Health and Wellness Center CRS
Dallas, Texas, United States
31473 Houston AIDS Research Team (HART) CRS
Houston, Texas, United States
University of Washington AIDS CRS (1401)
Seattle, Washington, United States
Hospital Nossa Senhora da Conceicao CRS (12201)
Porto Alegre, Rio Grande do Sul, Brazil
Instituto de Pesquisa Clinica Evandro Chagas (12101)
Rio de Janeiro, , Brazil
Malawi CRS (12001)
Lilongwe, , Malawi
San Miguel CRS (11302)
San Isidro, Lima region, Peru
Barranco CRS
Lima, , Peru
31802 Thai Red Cross AIDS Research Center Treatment (TRC-ARC Treatment) CRS
Bangkok, Patumwan, Thailand
Milton Park CRS (30313)
Harare, , Zimbabwe
Countries
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References
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Crowell TA, Ritz J, Coombs RW, Zheng L, Eron JJ, Mellors JW, Dragavon J, van Zyl GU, Lama JR, Ruxrungtham K, Grinsztejn B, Arduino RC, Fox L, Ananworanich J, Daar ES; AIDS Clinical Trials Group A5354/EARLIER (Early ART to Limit Infection and Establishment of Reservoir) Study Team. Novel Criteria for Diagnosing Acute and Early Human Immunodeficiency Virus Infection in a Multinational Study of Early Antiretroviral Therapy Initiation. Clin Infect Dis. 2021 Aug 2;73(3):e643-e651. doi: 10.1093/cid/ciaa1893.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Document Type: Informed Consent Form
Related Links
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The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.1, July 2017
Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010
Other Identifiers
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ACTG A5354
Identifier Type: -
Identifier Source: org_study_id
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