What is the mechanism of action of this treatment?

The most common treatments for HIV/AIDS involve antiretroviral therapy (ART), which includes a combination of drugs that target different stages of the HIV life cycle. These drugs work by inhibiting enzymes essential for viral replication, such as reverse transcriptase, protease, and integrase, thereby reducing viral load and preventing disease progression. Recently, JAK 1/2 inhibitors like Baricitinib have been studied for their potential to reduce HIV persistence in the central nervous system (CNS) by crossing the blood-brain barrier and decreasing inflammation. This is significant for HIV/AIDS patients as it addresses one of the major challenges in eradicating the virus—its reservoirs in the CNS, which are not fully targeted by traditional ART.

What side effects are associated with this type of intervention?

Common treatments for HIV/AIDS primarily involve combination antiretroviral therapy (cART), which includes various classes of drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs). Known side effects of these treatments can include gastrointestinal issues (nausea, diarrhea), fatigue, headache, and more severe complications like liver toxicity, renal impairment, and cardiovascular issues. Baricitinib, a JAK 1/2 inhibitor being studied for its potential to reduce HIV persistence in the CNS, may have side effects such as increased risk of infections, elevated liver enzymes, and blood clotting issues, similar to its use in treating rheumatoid arthritis.

What prior FDA approvals exist?

The FDA has approved various antiretroviral therapies (ART) for the treatment of HIV/AIDS, which primarily focus on inhibiting different stages of the HIV life cycle. These include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry inhibitors. While Baricitinib, a JAK 1/2 inhibitor, is being studied for its potential to reduce HIV persistence in the CNS, there are no specific FDA-approved JAK inhibitors for HIV treatment as of now. Current ART regimens do not eliminate HIV reservoirs, including those in the CNS, which is a significant barrier to curing the infection.

What other types of research exist?

Promising novel alternatives to Baricitinib for HIV/AIDS patients include: 1) Long-acting injectable antiretrovirals such as Cabotegravir and Rilpivirine, which are in advanced clinical trials and offer sustained drug levels that may help in targeting HIV reservoirs. 2) Broadly neutralizing antibodies (bNAbs) like VRC01, which are being investigated for their potential to target and eliminate HIV-infected cells. 3) Latency-reversing agents (LRAs) such as Vorinostat, which aim to activate and eliminate latent HIV reservoirs. These alternatives are being studied for their efficacy in reducing HIV persistence, including in the CNS.

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Janus Kinase (JAK) Inhibitor

Baricitinib for HIV/AIDS

Phase 2

Recruiting

Led By William Tyor, MD

Research Sponsored by William Tyor

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline and study week 10

Awards & highlights

Approved for 5 Other Conditions

All Individual Drugs Already Approved

Summary

This trial tests if baricitinib, a pill for arthritis, can reduce HIV in the brain. It targets people with HIV on treatment who still have HIV in their brain. The drug works by entering the brain and lowering HIV levels.

Who is the study for?

This trial is for adults with HIV/AIDS who have been on antiretroviral therapy (ART) with undetectable viral loads for at least a year and have CD4+ counts over 350. Women must use contraception or be postmenopausal. Exclusions include those under 18 or over 65, history of blood clots, stroke, heart failure, liver cirrhosis, recent serious infections including COVID-19, certain cancers, major surgery within the last two months or planned during the study.

What is being tested?

The trial tests Baricitinib's ability to reduce HIV in the central nervous system compared to a placebo. Participants will undergo bloodwork, neurocognitive testing, MRIs and lumbar punctures to assess changes in CNS HIV levels and any improvements in brain function and inflammation markers.

What are the potential side effects?

Potential side effects of Baricitinib may include infection risk due to immune suppression; possible impact on liver enzymes; blood disorders like low hemoglobin or platelets; increased cholesterol levels; nausea; headaches; allergic reactions including rash.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline and study week 10

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline and study week 10

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline and study week 10 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Changes in CSF HIV RNA by single copy assay

Changes in CSF HIV cell associated CSF HIV DNA by Double-R assay

Biological Assay

+3 more

Secondary study objectives

Change in HIV DNA levels by Integrated proviral DNA assay

Mental Depression

Changes in Blood CXCL10

+20 more

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: BaricitinibExperimental Treatment1 Intervention

Potential participants will be pre-screened through review of the electronic medical record from Emory or Grady. Or if a potential participant receives care elsewhere, a release of medical information form will be signed and sent to the medical center that the individual goes to. The study team will enroll individuals who have well controlled HIV. Participants will then be randomized to either baricitinib or placebo. Patients randomized to Baricitinib group will receive Baricitinib at dose of 2 mg oral for ten weeks. Follow up visits will happen for both groups at weeks 1, 2, 4 and 10.

Group II: PlaceboPlacebo Group1 Intervention

Potential participants will be pre-screened through review of the electronic medical record from Emory or Grady. Or if a potential participant receives care elsewhere, a release of medical information form will be signed and sent to the medical center that the individual goes to. The study team will enroll individuals who have well controlled HIV. Participants will then be randomized to either baricitinib or placebo. Patients randomized to the placebo group will receive 2 mg oral daily placebo for ten weeks. Follow up visits will happen for both groups at weeks 1, 2, 4 and 10.

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for HIV/AIDS involve antiretroviral therapy (ART), which includes a combination of drugs that target different stages of the HIV life cycle. These drugs work by inhibiting enzymes essential for viral replication, such as reverse transcriptase, protease, and integrase, thereby reducing viral load and preventing disease progression. Recently, JAK 1/2 inhibitors like Baricitinib have been studied for their potential to reduce HIV persistence in the central nervous system (CNS) by crossing the blood-brain barrier and decreasing inflammation. This is significant for HIV/AIDS patients as it addresses one of the major challenges in eradicating the virus—its reservoirs in the CNS, which are not fully targeted by traditional ART.

Lessons learned from HIV treatment interruption: safety, correlates of immune control, and drug sparing.Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults.