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

Immediate Initiation of Antiretroviral Therapy During Acute HIV Infection

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.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV
• Intervention / Treatment: Drug: Dolutegravir; Drug: Emtricitabine/Tenofovir

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 Type: Interventional
• Enrollment (Estimated): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • San Francisco General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Tivicay; Drug: Emtricitabine/Tenofovir; Emtricitabine 200 mg/Tenofovir alafenamide 25 mg PO daily; Other Names: Truvada

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of immediate Dolutegravir plus Emtricitabine/Tenofovir administered to acutely infected HIV patients.	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HIV reservoir size (cell-associated total DNA) in peripheral blood	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.	5 years
Change in HIV reservoir size (cell-associated integrated DNA) in peripheral blood	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.	5 years
Change in HIV reservoir size (cell-associated unspliced RNA) in peripheral blood	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.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HIV reservoir size (cell-associated total DNA) in blood CD4+ subsets	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.	6 months
Change in HIV reservoir size (cell-associated integrated DNA) in blood CD4+ subsets	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.	5 years
Change in HIV reservoir size (cell-associated unspliced RNA) in blood CD4+ subsets	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.	6 months
Change in HIV reservoir size (cell-associated total DNA) in GALT CD4+ subsets	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.	6 months
Change in HIV reservoir size (cell-associated integrated DNA) in GALT CD4+ subsets	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.	5 years
Change in HIV reservoir size (cell-associated unspliced RNA) in GALT CD4+ subsets	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.	5 years

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Gilead Sciences; ViiV Healthcare
• Investigators: Principal Investigator: Sulggi Lee, MD PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: December 31, 2015
• First Submitted That Met QC Criteria: January 13, 2016
• First Posted (Estimated): January 15, 2016

Study Record Updates

• Last Update Posted (Actual): June 15, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: immediate antiretroviral therapy; hyperacute infection
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Infections; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Tenofovir; Emtricitabine; Dolutegravir
• Other Study ID Numbers: IN-US-236-1354

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No