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Immediate Initiation of Antiretroviral Therapy During "Hyperacute" HIV Infection (DGVTRU)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by University of California, San Francisco
Sponsor:
Collaborators:
ViiV Healthcare
Gilead Sciences
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT02656511
First received: December 31, 2015
Last updated: September 13, 2016
Last verified: September 2016
  Purpose
The purpose of this study is to identify and provide immediate antiretroviral therapy to a cohort of HIV-infected individuals with "hyperacute" infection (estimated date of HIV infection within the last 30 days). The primary aim of the study is to evaluate whether initiation of dolutegravir plus emtricitabine/tenofovir during hyperacute HIV infection leads to protection of CD4+ T cells in the peripheral blood and gut-associated lymphoid tissue from infection.

Condition Intervention Phase
HIV
Drug: Dolutegravir
Drug: Emtricitabine/Tenofovir
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Immediate Initiation of Antiretroviral Therapy During "Hyperacute" HIV Infection

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Safety and tolerability of immediate Dolutegravir plus Emtricitabine/Tenofovir administered to acutely infected HIV patients. [ Time Frame: 6 months ]
    The number of grade 2 or higher severity adverse events (AEs) or drug-related laboratory abnormalities that exceed a frequency of 5% over a 6 month study period.


Secondary Outcome Measures:
  • Change in HIV reservoir size (cell-associated total DNA) in peripheral blood [ Time Frame: 6 months ]
    The change in HIV reservoir size (as measured by cell-associated total DNA levels in peripheral blood mononuclear cells) over a 6 month study period.

  • Change in HIV reservoir size (cell-associated integrated DNA) in peripheral blood [ Time Frame: 6 months ]
    The change in HIV reservoir size (as measured by cell-associated integrated DNA levels in peripheral blood mononuclear cells) over a 6 month study period.

  • Change in HIV reservoir size (cell-associated unspliced RNA) in peripheral blood [ Time Frame: 6 months ]
    The change in HIV reservoir size (as measured by cell-associated unspliced RNA levels in peripheral blood mononuclear cells) over a 6 month study period.


Other Outcome Measures:
  • Change in HIV reservoir size (cell-associated total DNA) in blood CD4+ subsets [ Time Frame: 6 months ]
    The change in HIV reservoir size (as measured by cell-associated total DNA levels in peripheral blood CD4+ T cell subsets) over a 6 month study period.

  • Change in HIV reservoir size (cell-associated integrated DNA) in blood CD4+ subsets [ Time Frame: 6 months ]
    The change in HIV reservoir size (as measured by cell-associated integrated DNA levels in peripheral blood CD4+ T cell subsets) over a 6 month study period.

  • Change in HIV reservoir size (cell-associated unspliced RNA) in blood CD4+ subsets [ Time Frame: 6 months ]
    The change in HIV reservoir size (as measured by cell-associated unspliced RNA levels in peripheral blood CD4+ T cell subsets) over a 6 month study period.

  • Change in HIV reservoir size (cell-associated total DNA) in GALT CD4+ subsets [ Time Frame: 6 months ]
    The change in HIV reservoir size (as measured by cell-associated total DNA levels in gut-associated lymphoid tissue [GALT] CD4+ T cell subsets) over a 6 month study period.

  • Change in HIV reservoir size (cell-associated integrated DNA) in GALT CD4+ subsets [ Time Frame: 6 months ]
    The change in HIV reservoir size (as measured by cell-associated integrated DNA levels in gut-associated lymphoid tissue [GALT] CD4+ T cell subsets) over a 6 month study period.

  • Change in HIV reservoir size (cell-associated unspliced RNA) in GALT CD4+ subsets [ Time Frame: 6 months ]
    The change in HIV reservoir size (as measured by cell-associated unspliced RNA levels in gut-associated lymphoid tissue [GALT] CD4+ T cell subsets) over a 6 month study period.


Estimated Enrollment: 24
Study Start Date: December 2015
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dolutegravir+Emtricitabine/Tenofovir
Dolutegravir 50 mg PO daily plus Emtricitabine 200 mg/Tenofovir disoproxil fumarate 300 mg PO daily
Drug: Dolutegravir
Dolutegravir 50 mg PO daily
Other Name: Tivicay
Drug: Emtricitabine/Tenofovir
Emtricitabine 200 mg/Tenofovir disoproxil fumarate 300 mg PO daily
Other Name: Truvada

Detailed Description:
Although ART decreases HIV-associated mortality, it does not appear to completely restore immune health, for reasons that remain unclear. In addition, while HIV prevention approaches have led to significant successes in decreasing the incidence of new HIV infection over the past few years, the epidemic continues to grow both locally and globally. A synergistic strategy to HIV prevention is to effectively eradicate virus from HIV-infected persons. While complete eradication may not currently be feasible, a "functional cure" in which patients are able to indefinitely maintain undetectable viral loads in the absence of therapy may be an attainable immediate goal. Studying hyperacute HIV-infected individuals will provide a unique opportunity to investigate the pathophysiology of the earliest stages of HIV infection and may help identify the virologic/immunologic predictors of a functional cure.
  Eligibility

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

Inclusion Criteria:

  1. Willing and able to provide written informed consent
  2. Male or female, age ≥18 years
  3. Acute HIV infection with a negative or indeterminate HIV-1 antibody test and plasma HIV-1 RNA > 40 cp/ml, OR clinical history consistent with new HIV infection in the last 30 days.
  4. Antiretroviral therapy untreated
  5. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
  6. All subjects must agree not to participate in a conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization)..
  7. When participating in sexual activity that could lead to pregnancy, female subjects must agree to use a doublebarrier method of contraception for at least two weeks after discontinuation of study drug.

Exclusion Criteria:

  1. Known severe kidney disease (CrCl < 60 ml/min via Cockcroft-Gault method)
  2. Known severe hepatic impairment (Child-Pugh Class C)
  3. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  4. Subjects with anticipated need for Hepatitis C virus (HCV) therapy during study
  5. Concurrent treatment with dofetilide, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St. John's wort, or metformin
  6. Serious illness requiring systemic treatment and/or hospitalization in the preceding 90 days prior to study enrollment
  7. Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drugs in the preceding 90 days prior to study enrollment (e.g. IL-2, interferon-alpha, methotrexate, cancer chemotherapy)
  8. Concurrent treatment with investigational drugs, or exposure to any investigational drugs in the preceding 90 days prior to study enrollment
  9. Active drug or alcohol use or dependence that, in the opinion of the Principal Investigator, would interfere with adherence to study requirements
  10. Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation
  11. Pregnant or breastfeeding women.
  12. For subjects who agree to colorectal biopsy
  13. Known blood coagulation disorder
  14. Platelets < 50,000/mm^3
  15. PTT > 2x upper limit of normal
  16. INR > 1.3
  17. Use of aspirin, NSAIDs, Plavix, Coumadin, or other blood thinners that cannot be stopped for clinical reasons for 5 days before and after each colorectal biopsy
  18. Inflammatory colitis (e.g., Crohn's disease and/or ulcerative colitis) and/or any contraindications to sigmoidoscopy or colorectal biopsy such as peritonitis, active diverticulitis, or recent bowel surgery
  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: NCT02656511

Contacts
Contact: Sulggi A Lee, MD PhD sulggi.lee@ucsf.edu
Contact: Steven G Deeks, MD Steven.Deeks@ucsf.edu

Locations
United States, California
San Francisco General Hospital Recruiting
San Francisco, California, United States, 94110
Contact: Sulggi A Lee, MD PhD       sulggi.lee@ucsf.edu   
Contact: Steven G Deeks, MD       Steven.Deeks@ucsf.edu   
Sponsors and Collaborators
University of California, San Francisco
ViiV Healthcare
Gilead Sciences
Investigators
Principal Investigator: Steven Deeks, MD U
  More Information

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02656511     History of Changes
Other Study ID Numbers: IN-US-236-1354
Study First Received: December 31, 2015
Last Updated: September 13, 2016

Keywords provided by University of California, San Francisco:
immediate antiretroviral therapy
hyperacute infection

Additional relevant MeSH terms:
Infection
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
Emtricitabine
Dolutegravir
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
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
HIV Integrase Inhibitors
Integrase Inhibitors

ClinicalTrials.gov processed this record on May 25, 2017