Immediate Initiation of Antiretroviral Therapy During "Hyperacute" HIV Infection

NCT ID: NCT02656511

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2028-05-31

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.

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.

Conditions

HIV

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dolutegravir+Emtricitabine/Tenofovir

Dolutegravir 50 mg PO daily plus Emtricitabine 200 mg/Tenofovir alafenamide 25 mg

Group Type: EXPERIMENTAL

Dolutegravir

Intervention Type: DRUG

Dolutegravir 50 mg PO daily

Emtricitabine/Tenofovir

Intervention Type: DRUG

Emtricitabine 200 mg/Tenofovir alafenamide 25 mg PO daily

Interventions

Dolutegravir

Dolutegravir 50 mg PO daily

Intervention Type: DRUG

Emtricitabine/Tenofovir

Emtricitabine 200 mg/Tenofovir alafenamide 25 mg PO daily

Intervention Type: DRUG

Other Intervention Names

Tivicay; Truvada

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sulggi Lee, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

San Francisco General Hospital

San Francisco, California, United States

Countries

United States

References

Whitehill GD, Joy J, Marino FE, Krause R, Mallick S, Courtney H, Park K, Carey J, Hoh R, Hartig H, Pae V, Sarvadhavabhatla S, Donaire S, Deeks SG, Lynch RM, Lee SA, Bar KJ. Autologous neutralizing antibody responses after antiretroviral therapy in acute and early HIV-1. J Clin Invest. 2024 Apr 23;134(11):e176673. doi: 10.1172/JCI176673.

Reference Type: DERIVED

PMID: 38652564 (View on PubMed)

Other Identifiers

IN-US-236-1354

Identifier Type: -

Identifier Source: org_study_id