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

• ClinicalTrials.gov Identifier: NCT02656511
• Recruitment Status: Active, not recruiting
• First Posted: January 15, 2016
• Last Update Posted: April 28, 2023
• Sponsor: University of California, San Francisco
• Collaborators: ViiV Healthcare; Gilead Sciences
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

Brief Summary:

The purpose of this study is to identify and provide immediate antiretroviral therapy to a cohort of HIV-infected individuals with very early HIV infection (estimated date of infection within the last 90 days). The primary aim of the study is to evaluate whether initiation of dolutegravir plus emtricitabine/tenofovir during acute/early HIV infection leads to protection of CD4+ T cells and other immune cells in the peripheral blood and lymphoid tissue from infection.

Condition or disease	Intervention/treatment	Phase
HIV	Drug: Dolutegravir; Drug: Emtricitabine/Tenofovir	Phase 4

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. 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 patients with early HIV infection and immediate ART 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 74 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Immediate Initiation of Antiretroviral Therapy During Acute HIV Infection
• Actual Study Start Date: December 2015
• Estimated Primary Completion Date: April 2024
• Estimated Study Completion Date: April 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dolutegravir+Emtricitabine/Tenofovir; Dolutegravir 50 mg PO daily plus Emtricitabine 200 mg/Tenofovir alafenamide 25 mg	Drug: Dolutegravir; Dolutegravir 50 mg PO daily; Other Name: Tivicay; Drug: Emtricitabine/Tenofovir; Emtricitabine 200 mg/Tenofovir alafenamide 25 mg PO daily; Other Name: Truvada

Outcome Measures

Primary Outcome Measures :

1. 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 :

1. Change in HIV reservoir size (cell-associated total DNA) in peripheral blood [ Time Frame: 5 years ]
   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.
2. Change in HIV reservoir size (cell-associated integrated DNA) in peripheral blood [ Time Frame: 5 years ]
   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.
3. Change in HIV reservoir size (cell-associated unspliced RNA) in peripheral blood [ Time Frame: 5 years ]
   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:

1. 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.
2. Change in HIV reservoir size (cell-associated integrated DNA) in blood CD4+ subsets [ Time Frame: 5 years ]
   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.
3. 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.
4. 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.
5. Change in HIV reservoir size (cell-associated integrated DNA) in GALT CD4+ subsets [ Time Frame: 5 years ]
   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.
6. Change in HIV reservoir size (cell-associated unspliced RNA) in GALT CD4+ subsets [ Time Frame: 5 years ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• 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 90 days.
4. Antiretroviral therapy untreated or recently initiated (within 7 days)
5. Participant must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
6. All participants 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 participants must agree to use a double barrier 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. Participants 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 participants 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

Locations

United States, California

San Francisco General Hospital

San Francisco, California, United States, 94110

Sponsors and Collaborators

University of California, San Francisco

ViiV Healthcare

Gilead Sciences

Investigators

• Principal Investigator: Sulggi Lee, MD PhD; University of California, San Francisco

More Information

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02656511
• Other Study ID Numbers: IN-US-236-1354
• First Posted: January 15, 2016
• Last Update Posted: April 28, 2023
• Last Verified: April 2023

Keywords provided by University of California, San Francisco:

immediate antiretroviral therapy; hyperacute infection

Additional relevant MeSH terms:

Infections; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Tenofovir; Emtricitabine; Dolutegravir; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors