Baricitinib Curative Repression of HIV-1

This study is being done to test whether a drug called baricitinib, which blocks specific causes of inflammation, affects HIV-1 viral rebound and viral load levels after HIV treatment is discontinued. Researchers will test the effects of continuing baricitinib in people with HIV before and after discontinuing their antiretroviral therapy. This drug is approved by the Food and Drug Administration (FDA) for other diseases; it is not approved for the treatment of HIV-1. The study team will also investigate any side effects associated with the drug.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Infection; HIV
• Intervention / Treatment: Drug: Antiretroviral Therapy (ART); Drug: Baricitinib (LY3009104) 2 mg

Detailed Description

This study will test whether the medication baricitinib, which reduces inflammation and is already approved for other diseases, can delay the return of HIV after stopping antiretroviral therapy (ART). The goal is to see if baricitinib can safely reduce inflammation and the HIV that is hidden in the body. The study will include adults with HIV who have a suppressed viral load on ART.

Participants will receive ART combined with baricitinib for 26 weeks, followed by baricitinib alone after stopping ART. If the virus returns, the previous ART will be restarted. Each participant will be involved in the study for approximately 12 to 18 months.

Blood and other biological samples may be stored for future research use, with the participant's consent.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vincent Marconi, MD; Phone Number: 404-616-0673; Email: vcmarco@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Grady Infectious Diseases Clinic (Ponce Center)
    • Atlanta, Georgia, United States, 30322
      • Dr. Gavegnano's Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Documented HIV infection
• On continuous ART for at least 96 weeks before enrollment, with no interruption of ART for 7 consecutive days or longer in the 48 weeks before enrollment.
• Plasma HIV-1 RNA levels of <50 copies/mL for at least 96 weeks (a minimum of two measures), and <50 copies/mL for a sample obtained within 90 days, before enrollment.
• CD4+ T-cell count ≥500 cells/mm3 obtained within 90 days prior to enrollment
• No known history of CD4+ T-cell count nadir <200 cells/mm3
• Negative pregnancy test at time of study enrollment
• Additional laboratory criteria may apply.

Exclusion Criteria:

• < 18 years of age or > 70 years of age
• Pregnancy or breastfeeding, as determined by a blood pregnancy test
• History of AIDS-defining illness, except for recurrent pneumonia.
• History of progressive multifocal leukoencephalopathy or clinically significant HIV-associated neurocognitive disease.
• Untreated latent tuberculosis infection (which will be screened for before entry). If there is a prior positive test, the test does not need to be repeated at screening.
• History of use of any immunomodulatory medications within 6 months before enrollment, including systemic corticosteroids (>14 days), immunosuppressants, anti-cancer, interleukins, systemic interferons, systemic chemotherapy, or other medications that the site investigator feels could have an immunomodulatory effect.
• History of deep venous thrombosis
• Cardiovascular disease (Coronary artery disease or history of myocardial infarction, Congestive heart failure with left ventricular ejection fraction ≤40% per American Heart Association guidelines, history of stroke)
• History of HIV-associated malignancy, including Kaposi's sarcoma, or any lymphoma/leukemia or virus-associated cancers. Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery in the preceding 36 months
• Major surgery within 8 weeks before screening, or will require major surgery during the study
• Current or recent (<4 weeks before screening) clinically serious viral (including COVID-19), bacterial, fungal, or parasitic infection or any other active or recent infection. History of untreated syphilis infection. If a rapid plasma reagin (RPR) test was negative in the 3 months before screening, then an RPR is not needed at screening
• Symptomatic herpes simplex at the time of screening.
• Symptomatic herpes zoster infection within 12 weeks before screening.
• History of disseminated/complicated herpes zoster (for example, ophthalmic zoster or central nervous system (CNS) involvement).
• Positive test for hepatitis B virus (HBV)
• Additional exclusion criteria apply

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: Baricitinib; Adults with well-controlled HIV on ART will be treated for 26 weeks with baricitinib 2 mg per day orally plus their current ART regimen (Step 1). Following 26 weeks of baricitinib plus ART, ART will be interrupted, and the participants will be treated with baricitinib alone for up to 24 weeks (Step 2). If a participant qualifies for ART restart criteria before the end of the maximum 24 weeks of Step 2, they will move to Step 3 early and resume ART, while baricitinib will be discontinued for 24 weeks. Otherwise, participants will remain on baricitinib alone until the end of the 24 weeks of Step 2 and will then resume ART while baricitinib is discontinued for an additional 24 weeks of observation (Step 3).

Drug: Antiretroviral Therapy (ART); Antiretroviral Therapy (ART): A treatment regimen for HIV infection that uses a combination of antiretroviral drugs to suppress viral replication, reduce HIV-related morbidity, and prevent transmission. In Step 1, participants will continue their current ART regimen for 26 weeks. In Step 2, participants will interrupt ART. In Step 3, participants will restart ART treatment early if they meet the ART restart criteria before the end of Step 2 (24-week maximum). Otherwise, they will resume ART at the end of Step 2.; Other Names: Standard of Care; Drug: Baricitinib (LY3009104) 2 mg; Baricitinib is an orally administered, selective inhibitor of Janus kinase (JAK) 1 and 2. It reduces cytokine-mediated signaling involved in inflammation and immune activation. Baricitinib is FDA-approved for rheumatoid arthritis (RA), atopic dermatitis, and alopecia areata. It has also been authorized for the treatment of COVID-19 in hospitalized patients. During Step 1, Baricitinib will be taken at a dose of 2 mg orally daily for 26 weeks. During Step 2, Baricitinib alone will be continued at a dose of 2 mg orally daily for up to an additional 24 weeks; Other Names: Olumiant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to restart ART	Time to restart ART will be defined by a plasma HIV-1 RNA viral load greater than or equal to 1000 copies/mL following withdrawal of ART during 24 weeks of baricitinib treatment alone (following 26 weeks of baricitinib plus ART).	Up to 24 weeks after the baricitinib treatment alone was started
Number of Participants who discontinued treatment due to adverse events	Participants who permanently discontinued study drug due to treatment-related adverse events.	Up to 24 weeks after the start of baricitinib alone was started
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants experiencing treatment-emergent adverse events (TEAEs), including serious adverse events.	Up to 24 weeks after the start of baricitinib alone was started

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to a detectable plasma HIV-1 RNA viral load	Time to a detectable plasma HIV-1 RNA viral load (defined as greater than the lower limit of quantification) after analytic treatment Interruption (ATI).	Up to 24 weeks after baricitinib alone was started.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Latent intact HIV reservoir	Latent intact HIV reservoir as measured in peripheral blood primarily by Intact Proviral DNA Assay (IPDA), integrated HIV-1 DNA (Alu-PCR), cell-associated RNA, and proviral DNA (total HIV cell-associated DNA).	Baseline and up to 24 week after baricitinib alone was started.

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Andrew H Miller, MD, Emory University; Principal Investigator: Vincent Marconi, MD, Emory University; Principal Investigator: William Tyor, MD, Emory University; Principal Investigator: Christina Gavegnano, PhD, Emory University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: October 2, 2025
• First Submitted That Met QC Criteria: October 2, 2025
• First Posted (Actual): October 6, 2025

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Baricitinib; Antiretroviral Therapy (ART)
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Health Services Administration; Health Care Quality, Access, and Evaluation; Therapeutics; Drug Therapy; Quality of Health Care; Quality Indicators, Health Care; Drug Therapy, Combination; Standard of Care; baricitinib; Antiretroviral Therapy, Highly Active
• Other Study ID Numbers: STUDY00009759; 2025P012728 (Other Identifier: Emory Insight Humans IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The research team will share the data that underline the results reported in articles, after deidentification
• IPD Sharing Time Frame: Data will be shared by the research team after the study has been completed.
• IPD Sharing Access Criteria: Requests should be sent directly to the PI via email, summarizing the purpose of utilizing the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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