Baricitinib for Reduction of HIV- CNS

• Status: Not yet recruiting
• Trial end date: 2027-07-01
• Target enrollment: 0
• Participant gender: All

Summary

There is still no cure for the human immunodeficiency virus (HIV). While combination antiretroviral therapy (cART) is effective in decreasing deaths from HIV, infected individuals face a lifetime of treatment and many potential complications including end organ diseases such as HIV-associated neurocognitive disorders. HIV infection is controllable with antiretroviral therapy (ART), but ART cannot eliminate HIV reservoirs. Thus, there is no available cure for HIV. There is a large and growing body of evidence that the central nervous system (CNS) is an HIV reservoir site and a barrier to HIV eradication. Our group has done extensive pre-clinical work with janus-kinase (JAK 1/2) inhibitors. This includes baricitinib, which is an orally available, FDA-approved drug for rheumatoid arthritis. Evidence suggests that this drug has activity against HIV in the central nervous system (CNS). In our recently completed pilot study, we showed that baricitinib crosses the blood brain barrier (BBB) and decreases HIV CNS persistence in the brain.

Using bloodwork, neurocognitive testing, MRIs and lumbar punctures, we plan to evaluate the change in central nervous system HIV after treatment with baricitinib versus placebo. We will also evaluate changes in neuroimaging, inflammation in blood and cerebrospinal fluid (CSF), and neuropsychological performance after treatment with baricitinib versus placebo.

Evidence shows that the central nervous system is one of the reservoir sites that enables the HIV virus to persist in the body even after years of treatment. In order to attack this reservoir and eventually find a cure, it is vital to learn if certain medications can suppress HIV in the CNS.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Emory University
• Collaborator: National Institute of Mental Health (NIMH)

Criteria

Inclusion Criteria:

1. HIV infected on continuous ART with plasma HIV RNA <200 copies/ml for at least 12 months (on at least two previous clinic visits and confirmed at screening).

2. Current CD4+ > 350 cells/microliter for at least twelve months (on at least two previous clinic visits and confirmed at screening).

3. Women of reproductive age will have a negative pregnancy test at study entry and agree to contraception while on study drug. Women who are at least 50 years of age and who have been amenorrheic for at least 12 months will not be required to agree to contraception to participate.

Exclusion Criteria:

1. < 18 years of age or > 65 years of age

2. Pregnancy or breastfeeding

3. Significant hematological abnormalities at screening (ANC < 1500, Hgb<10, platelet< 100,000)

4. History of progressive multifocal leukoencephalopathy

5. Untreated latent tuberculosis infection (which will be screened for prior to entry)

6. Immunosuppressive medications (including corticosteroids) and anticoagulants (aspirin acceptable)

7. History of deep venous thrombosis

8. Cardiovascular disease:

1. Coronary artery disease or history of myocardial infarction

2. Congestive heart failure with left ventricular ejection fraction ≤40% per American Heart Association guidelines75

3. Stroke history

9. Hematologic malignancies including lymphoma and leukemia

10. Major surgery within 8 weeks prior to screening or will require major surgery during the study

11. Current or recent (<4 weeks prior to randomization) clinically serious viral (including COVID-19), bacterial, fungal, or parasitic infection or any other active or recent infection

12. Symptomatic herpes simplex at the time of randomization

13. Symptomatic herpes zoster infection within 12 weeks prior to randomization.

14. History of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement).

15. Positive test for hepatitis B virus (HBV) defined as:

1. positive for hepatitis B surface antigen (HBsAg), or

2. positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B virus deoxyribonucleic acid (HBV DNA)

16. Hepatitis C virus (HCV) infection (hepatitis C antibody-positive and HCV ribonucleic acid [RNA]-positive).

17. Cirrhosis of the liver from any cause

18. Any of the following specific abnormalities on screening laboratory tests:

1. ALT or AST >2 x upper limits of normal (ULN)

2. alkaline phosphatase (ALP) ≥2 x ULN

3. total bilirubin ≥1.5 x ULN (with the exception of patients on atazanavir, who must have total bilirubin <2 x ULN)

19. Chronic kidney disease with eGFR <40 mL/min/1.73 m2 (note that dose of baricitinib will be reduced to 1 mg daily in participants with GFR between 40 and 60).

20. Current dependence on illicit drugs except for marijuana

21. Population: The study team will not include any of the following groups:

• Adults unable to consent

• Individuals who are not yet adults (infants, children, teenagers)

• Pregnant women

• Prisoners

• Cognitively impaired or Individuals with Impaired Decision-Making Capacity

• Individuals who are not able to clearly understand English

• Community Participation (if applicable)