Immediate Initiation of Antiretroviral Therapy During "Hyperacute" HIV Infection

NCT02656511 | Active Not Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: IN-US-236-1354
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV

Keywords

immediate antiretroviral therapy; hyperacute infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in HIV reservoir size (cell-associated total DNA) in peripheral blood

  5 years

• Change in HIV reservoir size (cell-associated integrated DNA) in peripheral blood

  5 years

• Change in HIV reservoir size (cell-associated unspliced RNA) in peripheral blood

  5 years

Other Outcomes (6)

• Change in HIV reservoir size (cell-associated total DNA) in blood CD4+ subsets

  6 months

• Change in HIV reservoir size (cell-associated integrated DNA) in blood CD4+ subsets

  5 years

• Change in HIV reservoir size (cell-associated unspliced RNA) in blood CD4+ subsets

  6 months

Study Arms (1)

Dolutegravir+Emtricitabine/Tenofovir

EXPERIMENTAL

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

Drug: Dolutegravir; Drug: Emtricitabine/Tenofovir

Interventions

Dolutegravir DRUG

Dolutegravir 50 mg PO daily

Also known as: Tivicay

Dolutegravir+Emtricitabine/Tenofovir

Emtricitabine/Tenofovir DRUG

Emtricitabine 200 mg/Tenofovir alafenamide 25 mg PO daily

Also known as: Truvada

Dolutegravir+Emtricitabine/Tenofovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• Male or female, age ≥18 years
• 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.
• Antiretroviral therapy untreated or recently initiated (within 7 days)
• Participant must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
• 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)..
• 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.

You may not qualify if:

• Known severe kidney disease (CrCl \< 60 ml/min via Cockcroft-Gault method)
• Known severe hepatic impairment (Child-Pugh Class C)
• 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)
• Participants with anticipated need for Hepatitis C virus (HCV) therapy during study
• Concurrent treatment with dofetilide, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St. John's wort, or metformin
• Serious illness requiring systemic treatment and/or hospitalization in the preceding 90 days prior to study enrollment
• 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)
• Concurrent treatment with investigational drugs, or exposure to any investigational drugs in the preceding 90 days prior to study enrollment
• Active drug or alcohol use or dependence that, in the opinion of the Principal Investigator, would interfere with adherence to study requirements
• Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation
• Pregnant or breastfeeding women.
• For participants who agree to colorectal biopsy
• Known blood coagulation disorder
• Platelets \< 50,000/mm\^3
• PTT \> 2x upper limit of normal

Sponsors & Collaborators

• University of California, San Francisco: lead
• ViiV Healthcare: collaborator
• Gilead Sciences: collaborator

Study Sites (1)

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Related Publications (1)

• 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.

  PMID: 38652564 DERIVED

MeSH Terms

Interventions

dolutegravir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Sulggi Lee, MD PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2015
• First Posted: January 15, 2016
• Study Start: December 1, 2015
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: June 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)