Early ART to Limit Infection and Establishment of Reservoir

NCT02859558 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: ACTG A53542UM1AI068636
• Study Type: interventional
• Target: 195
• Locations: 6 countries
• Sites: 30

Brief Summary

The study was done to:

• 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

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Undetectable Cell-associated HIV-1 DNA (CAHD)

  Proportion of participants with 0 copies of CAHD per 5 million CD4+ blood-derived CD4+ T-cells (assayed by quantitative polymerase chain reaction \[qPCR\]), assessed separately and jointly by integrase and gag assays. In order for a participant to be considered as having 0 copies of CAHD for joint assays, the participant must be found to have an undetectable CAHD result from both integrase and gag assays. If all participants in both arms had undetectable CAHD then the statistical test was not performed.

  At week 48

Secondary Outcomes (3)

• HIV-1-specific CD4+ and T-cell Responses to Nef, Gag, Pol and Env by Flow Cytometry

  At week 48

• HIV-1-specific CD8+ and T-cell Responses to Nef, Gag, Pol and Env by Flow Cytometry

  At 48 weeks

• Proportion of Participants With Undetectable Cell-associated HIV-1 DNA (CAHD) Prior to ART Initiation

  At week 0

Study Arms (3)

Arm 1: Fiebig I/II

EXPERIMENTAL

Participants enrolled during Fiebig stages I or II (non-reactive HIV-1 antibody).

Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy

Arm 2: Fiebig III/IV

EXPERIMENTAL

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).

Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy

Arm 3: Fiebig V

EXPERIMENTAL

Participants enrolled during Fiebig stage V (reactive HIV-1 antibody and positive Western blot or Geenius HIV-1/HIV-2 without p31 band).

Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy

Interventions

elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide or other medically-appropriate FDA-approved antiretroviral therapy DRUG

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.

Also known as: Single-tablet regimen EVG/COBI/FTC/TAF or Genvoya, Single-tablet regimen BIC/FTC/TAF or Biktarvy

Arm 1: Fiebig I/II; Arm 2: Fiebig III/IV; Arm 3: Fiebig V

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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
• 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
• 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
• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (30)

31788 Alabama CRS

Birmingham, Alabama, 35294, United States

Location

Ucsd, Avrc Crs (701)

San Diego, California, 92103, United States

Location

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, 90502, United States

Location

Whitman Walker Health CRS (31791)

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

Location

The Ponce de Leon Center CRS (5802)

Atlanta, Georgia, 30308, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

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

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, 02115, United States

Location

Washington University CRS (2101)

St Louis, Missouri, 63110, United States

Location

31786 New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

7804 Weill Cornell Chelsea CRS

New York, New York, 10010, United States

Location

Columbia Physicians and Surgeons CRS (30329)

New York, New York, 10032, United States

Location

3201 Chapel Hill CRS

Chapel Hill, North Carolina, 27516, United States

Location

Greensboro CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, 43210, United States

Location

6201 Penn Therapeutics CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hosp. ACTG CRS (2951)

Providence, Rhode Island, 02906, United States

Location

31443 Trinity Health and Wellness Center CRS

Dallas, Texas, 75208, United States

Location

31473 Houston AIDS Research Team (HART) CRS

Houston, Texas, 77030, United States

Location

University of Washington AIDS CRS (1401)

Seattle, Washington, 98104, United States

Location

Hospital Nossa Senhora da Conceicao CRS (12201)

Porto Alegre, Rio Grande do Sul, 9043010, Brazil

Location

Instituto de Pesquisa Clinica Evandro Chagas (12101)

Rio de Janeiro, 21045, Brazil

Location

Malawi CRS (12001)

Lilongwe, Malawi

Location

San Miguel CRS (11302)

San Isidro, Lima region, Peru

Location

Barranco CRS

Lima, 18, Peru

Location

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

Bangkok, Patumwan, 10330, Thailand

Location

Milton Park CRS (30313)

Harare, Zimbabwe

Location

Related Publications (1)

• 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.

  PMID: 33382405 DERIVED

Related Links

• 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

MeSH Terms

Interventions

elvitegravir; bictegravir, emtricitabine, tenofovir alafenamide, drug combination; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 9, 2016
• Study Start: January 24, 2017
• Primary Completion: December 2, 2020
• Study Completion: April 16, 2025
• Last Updated: August 29, 2025
• Results First Posted: January 3, 2022

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the Advancing Clinical Therapeutics Globally (ACTG) by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG. * For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data.

Locations

BR (2); TH (1); US (23); PE (2); ZI (1); MA (1)