Immediate Initiation of Antiretroviral Therapy During "Hyperacute" HIV Infection

HIV Clinical Trial

— DGVTAF  

Official title:

Immediate Initiation of Antiretroviral Therapy During Acute HIV Infection

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02656511
• Other study ID #: IN-US-236-1354
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: December 2015
• Est. completion date: May 2028

Study information

• Verified date: May 2024
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 74
• Est. completion date: May 2028
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV
• HIV Infections
• Infections

Intervention

Drug:
• Dolutegravir
Dolutegravir 50 mg PO daily
• Emtricitabine/Tenofovir
Emtricitabine 200 mg/Tenofovir alafenamide 25 mg PO daily

Locations

Country	Name	City	State
United States	San Francisco General Hospital	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	Gilead Sciences, ViiV Healthcare

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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