A Phase 2 interventional study of Baricitinib 2 MG Oral Tablet and Placebo in Human Immunodeficiency Virus, sponsored by William Tyor. Recruiting at 2 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-03-23.
Sponsored by William Tyor · Phase 2, Interventional, and Treatment
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.
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. HIV DNA is commonly found in brain from people with HIV (PWH) on suppressive ART. HIV genetic compartmentalization occurs in both the brain and CSF, showing that CNS HIV is distinct from peripheral sources such as blood. Multiple studies have demonstrated that CSF HIV RNA can be detected at very low levels during suppressive ART. A study from the AIDS Clinical Trials Group (ACTG) found HIV DNA in CSF cells from approximately 50% of PWH on suppressive ART, a finding that was associated with neurocognitive impairment. The study team's group recently demonstrated a significant advance in quantitating HIV from the CSF. Specifically, CSF cell associated HIV RNA was quantifiable in 90% and CSF HIV DNA was quantifiable in 80% of PWH on suppressive ART. Based on these multiple lines of evidence that the CNS is an HIV reservoir, more research is needed on therapies that have the potential to target the CNS reservoir.
The study team has performed extensive pre-clinical and clinical work on the Janus Kinase (Jak 1/2) inhibitor drug class for viral infections. This includes work on ruxolitinib and baricitinib, two FDA approved orally bioavailable agents for myelofibrosis and polycythemia vera (ruxolitinib) as well as rheumatoid arthritis (baricitinib). The investigators have evaluated their potential to target HIV in the CNS in vitro, ex vivo, and in vivo Specifically, the study team has demonstrated that these agents block HIV replication and infection in key CNS cells, reduce the lifespan of HIV CNS reservoirs, and block reservoir reseeding. In vivo, the study team has shown in the murine model that baricitinib decreases CNS HIV and reverses behavioral abnormalities associated with HIV, which correlates with reversal of phenotypic markers of brain inflammation. This has also demonstrated that baricitinib reaches therapeutic CNS concentrations in the rhesus macaque model (including in brain parenchyma) as well as in humans. In a recently published multi-site Phase 2a ACTG-sponsored study with ruxolitinib (A5336, n = 60),the research group demonstrated that ruxolitinib is safe, well-tolerated, and reduces key markers of immune activation. New data that ruxolitinib decreased the peripheral HIV reservoir in a subset of A5336 participants provides even more evidence for this drug class to be included in eradication strategies. However, A5336 did not have any CNS assessments. The investigators now propose to study baricitinib, one of the most promising Jak 1/2 inhibitors with once daily dosing, renal clearance, and a more favorable safety/ pharmacokinetic profile, as a therapy to decrease the HIV CNS reservoir in PWH with durable virologic suppression on ART.
2,040 studies on the registry are indexed under Acquired Immunodeficiency Syndrome; 272 are open to participants now.
This study's planned enrollment of 95 is close to the median of 105 across 1,543 interventional studies indexed under Acquired Immunodeficiency Syndrome.
Browse Acquired Immunodeficiency Syndrome studies →This is the only study on the registry with William Tyor as lead sponsor.
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Exclusion Criteria:
Cardiovascular disease:
Positive test for hepatitis B virus (HBV) defined as:
Any of the following specific abnormalities on screening laboratory tests:
Population: The study team will not include any of the following groups:
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.
Drug: Baricitinib 2 MG Oral Tablet
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.
Drug: Placebo
Baricitinib, a Janus Kinase inhibitor drug for viral infections, will be administered orally to subjects randomized to this intervention. The dose will be 2 mg orally for ten weeks. This will be compared with placebo intervention. Follow up visits will take place at week 1,2,4 and 10.
Also known as: Baricitinib
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.
Changes in CSF integrated proviral DNA
The study team will obtain up to 40 milliliters (ml) of CSF from individuals who weigh at least 60 kilograms, otherwise, they will draw up to 30 ml of CSF. CSF integrated proviral DNA (IPDA and Alu-PCR) will be assessed: Integrated proviral DNA will be performed using existing methods in the clinical research group, which employ the Alu-PCR real-time platform, with a limit of 3 copies. Integrated proviral DNA assay (IPDA) to measure the replication-competent reservoir will be used with digital droplet PCR methodology.
Time frame: Baseline and study week 10
Changes in CSF HIV RNA by single copy assay
This method is based on a proprietary protocol which is used in conjunction with a commercial HIV-1 RNA easyQ reagent kit (bioMerieux Inc, Lyon, France). Briefly, a specimen of up to 2 ml of human plasma or CSF is added to lysis buffer containing guanidine thiocyanate. HIV-1 RNA is extracted in combination with the easyMAG platform (bioMerieux, Inc). Eluates containing HIV-1 RNA are aliquoted into 0.5 mL reaction tubes and amplified using 3 enzymes: T7 RNA polymerase, avian myeloblastosis virus reverse transcriptase, and RNase H. Molecular beacons targeting the pol/gag region of HIV-1 RNA are used for amplification and detection by isothermal reactions at 41oC. HIV-1 RNA level is quantified in conjunction with the NucliSENS easyQ HIV-1 v2.0 Director software and a proprietary algorithm developed by bioMONTR Labs. The dynamic range of this HIV-1 assay is 1-5,000,000 copies/mL of 0.73 - 1600 HIV-1 copies /μl. The HIV-1 copy number is normalized per one million of WBCs.
Time frame: Baseline and study week 10
Changes in HIV tat protein in CSF
The study team will obtain up to 40 milliliters (ml) of CSF from individuals who weigh at least 60 kilograms, otherwise we will draw up to 30 ml of CSF. HIV Tat in the CSF will be quantified according to published methods for ELISA to measure HIV Tat in human CSF.
Time frame: Baseline and study week 10
Changes in CSF HIV cell-associated RNA by Double-R assay.
The study team will obtain up to 40 milliliters (ml) of CSF from individuals who weigh at least 60 kilograms, otherwise, they will draw up to 30 ml of CSF. Briefly, after the isolation of Peripheral blood mononuclear cells (PBMC) and cells from CSF, samples will be resuspended in phosphate-buffered saline and stored for shipment in O-ring tubes. RNA will then be extracted using the Maxwell rapid sample concentrator (RSC) automated extraction platform. White Blood Cells (WBC) will be counted after red blood cell lysis using TC20 Automated Cell Counter, and these counts will be used to normalize the HIV-1 RNA results as copy numbers/106 cells. HIV-1 copy number per patient sample, in duplicate, is determined from a standard curve generated with HIV-1 plasmid controls, with a range of 0.73 - 1600 HIV-1 copies /μl. The HIV-1 copy number is normalized per one million of WBCs.
Time frame: Baseline and study week 10
Changes in CSF HIV cell associated CSF HIV DNA by Double-R assay.
The study team will obtain up to 40 milliliters (ml) of CSF from individuals who weigh at least 60 kilograms, otherwise they will draw up to 30 ml of CSF. Briefly, after the isolation of Peripheral blood mononuclear cells (PBMC) and cells from CSF, samples will be resuspended in phosphate-buffered saline and stored for shipment in O-ring tubes. DNA will then be extracted using the Maxwell rapid sample concentrator (RSC) automated extraction platform. WBCs will be counted after red blood cell lysis using TC20 Automated Cell Counter, and these counts will be used to normalize the HIV-1 DNA results as copy numbers/106 cells. HIV-1 copy number per patient sample, in duplicate, is determined from a standard curve generated with HIV-1 plasmid controls, with a range of 0.73 - 1600 HIV-1 copies /μl. The HIV-1 copy number is normalized per one million of WBCs.
Time frame: Baseline and study week 10
Changes in CSF cell associated DNA
The study team will obtain up to 40 milliliters (ml) of CSF from individuals who weigh at least 60 kilograms, otherwise we will draw up to 30 ml of CSF. Cell associated DNA will be performed according to standard existing protocols using real-time PCR with a limit of detection of five copies.
Time frame: Baseline and study week 10
Changes in Blood HIV cell associated RNA by Double-R assay
Changes in the blood between baseline and week ten after study medication. Briefly, after isolation of Peripheral blood mononuclear cells (PBMC) and cells from patient's blood sample, samples will be resuspended in phosphate buffered saline and stored for shipment in O-ring tubes. RNA will then be extracted using the Maxwell rapid sample concentrator (RSC) automated extraction platform. WBCs will be counted after red blood cell lysis using TC20 Automated Cell Counter, and these counts will be used to normalize the HIV-1 RNA results as copy numbers/106 cells. HIV-1 copy number per patient sample, in duplicate, is determined from a standard curve generated with HIV-1 plasmid controls, with a range of 0.73 - 1600 HIV-1 copies /μl. The HIV-1 copy number is normalized per one million of WBCs.
Time frame: Baseline and study week 10
Changes in Blood HIV cell associated DNA by Double-R assay
Changes in the blood between baseline and week ten after study medication. Briefly, after isolation of Peripheral blood mononuclear cells (PBMC) and cells from the patient's blood sample, samples will be resuspended in phosphate buffered saline and stored for shipment in O-ring tubes. DNA will then be extracted using the Maxwell rapid sample concentrator (RSC) automated extraction platform. WBCs will be counted after red blood cell lysis using TC20 Automated Cell Counter, and these counts will be used to normalize the HIV-1 DNA results as copy numbers/106 cells. HIV-1 copy number per patient sample, in duplicate, is determined from a standard curve generated with HIV-1 plasmid controls, with a range of 0.73 - 1600 HIV-1 copies /μl. The HIV-1 copy number is normalized per one million of WBCs.
Time frame: Baseline and study week 10
Changes in Blood cell associated DNA
Change in the blood between baseline and week ten after study medication. Cell associated DNA will be performed according to standard existing protocols using real-time PCR with a limit of detection of five copies.
Time frame: Baseline and study week 10
Change in HIV DNA levels by Integrated proviral DNA assay
Change in the blood between baseline and week ten after study medication. The study team will obtain up to 40 milliliters (ml) of CSF from individuals who weigh at least 60 kilograms, otherwise we will draw up to 30 ml of CSF. Blood integrated proviral DNA (IPDA and Alu-PCR) will be assessed: Integrated proviral DNA will be performed using existing methods in our group, which employ the Alu-PCR real-time platform, with a limit of 3 copies. Integrated proviral DNA assay (IPDA) to measure the replication competent reservoir will be used with digital droplet PCR methodology
Time frame: Baseline and study week 10
Changes in Blood HIV RNA by single copy assay
This method is based on a proprietary protocol which is used in conjunction with a commercial HIV-1 RNA easyQ reagent kit (bioMerieux Inc, Lyon, France). Briefly, a specimen of up to 2 ml of human plasma or CSF is added to lysis buffer containing guanidine thiocyanate. HIV-1 RNA is extracted in combination with the easyMAG platform (bioMerieux, Inc). Eluates containing HIV-1 RNA are aliquoted into 0.5 mL reaction tubes and amplified using 3 enzymes: T7 RNA polymerase, avian myeloblastosis virus reverse transcriptase, and RNase H. Molecular beacons targeting the pol/gag region of HIV-1 RNA are used for amplification and detection by isothermal reactions at 41oC. HIV-1 RNA level is quantified in conjunction with the NucliSENS easyQ HIV-1 v2.0 Director software and a proprietary algorithm developed by bioMONTR Labs. The dynamic range of this HIV-1 assay is 1-5,000,000 copies/mLof 0.73
Time frame: Baseline and study week 10
Changes in Blood indirect viral markers: anti-HIV antibody levels
Change in HIV and inflammation levels in the blood between baseline and week ten after study medication. Blood HIV antibodies by LIPS assay (gp120, integrase, protease, and p24) will be assayed. The LIPS assay uses recombinant chimeric fusion proteins with luciferase producing light and specific antigens for quantitative detection of antibodies.
Time frame: Baseline and study week 10
Changes in Blood indirect viral markers: HIV specific T cells
Change in HIV and inflammation levels in the blood between baseline and week ten after study medication Fresh Human peripheral blood mononuclear cells (PBMC) will be cultured in the presence or absence of overlapping peptides which induces broad, non-specific T-cell activation. In addition to cytokine production (focusing on TNFα, IFNγ, and IL-6 measured with Quanterix technology). Researchers will measure cell surface markers by flow cytometry.
Time frame: Baseline and study week 10
Changes in Blood CXCL10
Change in levels in the blood between baseline and week ten after study medication. The study team will measure CXCL10 from participants blood samples, in the setting of HIV using single molecule array technology by Quanterix.
Time frame: Baseline and study week 10
Changes in Blood Neopterin
Change in levels in the blood between baseline and week ten after study medication. The study team will measure neopterin in the setting of HIV using the enzyme linked immunosorbent assays produced by Uman diagnostics, R\&D Systems (ultra-sensitive), and Themo Fisher.
Time frame: Baseline and study week 10
Changes in Blood IL-7
Change in levels in the blood between baseline and week ten after study medication. This will be measured using mesoscale discovery platform.
Time frame: Baseline and study week 10
Changes in Blood IL-15
Change in levels in the blood between baseline and week ten after study medication. This will be measured using mesoscale discovery platform.
Time frame: Baseline and study week 10
Changes in Stroop Test (Color Naming and Color-Word)
In psychology, the Stroop effect is the delay in reaction time between congruent and incongruent stimuli. The effect has been used to create a psychological test (the Stroop test) that is widely used in clinical practice and investigation. A basic task that demonstrates this effect occurs when there is a mismatch between the name of a color (e.g., "blue", "green", or "red") and the color it is printed on (i.e., the word "red" printed in blue ink instead of red ink). When asked to name the color of the word it takes longer and is more prone to errors when the color of the ink does not match the name of the color. Word, color, and color-word T-Scores of 40 or less are considered "low." Word, color, and color-word T-Scores above 40 or are considered "normal." In order for one score to be considered "higher" or "lower" than another, a 10 point or greater T score difference is required.
Time frame: Baseline and study week 10
Changes in Hopkins Verbal Learning Test II (Learning and Recall)
This will be performed in a quiet exam room. Participants will have the opportunity to take breaks as needed and snacks will be provided. The Hopkins Verbal Learning Test-Revised (HVLT-R) is used to assess acquisition and delayed recall. The HVLT-R is a list learning test, which consists of 12 nouns within three semantic groups. The acquisition variable consists of three acquisition trials in which the administrator reads the words aloud and then asks the child to repeat as many as he/she can remember in any order. A delayed recall trial is introduced after 20-25 min, in which the child is asked to simply retrieve as many of the words listed in the acquisition trial as he/she can remember. The children are not informed about the delayed recall trial beforehand. Lower raw scores indicate difficulties with the task.
Time frame: Baseline and study week 10
Changes in Brief Visuospatial Test (Learning and Recall)
The Brief Visuospatial Memory Test (BVMT) is a commonly used assessment tool to measure visuospatial learning and memory abilities. In three Learning Trials, the respondent views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Last, a Recognition Trial, in which the respondent is asked to identify which of 12 figures were included among the original geometric figures, is administered. An optional Copy Trial may be administered to screen for severe visuoconstructive deficits and to help in scoring recall responses. 12 scores may be derived from BVMT-R performance. Recall performance is recorded for each of the immediate recall trials (Trial 1, Trail 2, and Trial 3) and for the delayed recall trial (Delayed Recall). The recall scores are combined to form three additional summary measures of learning and memory.
Time frame: Baseline and study week 10
Changes in Trailmaking
The Trail Making Test is a neuropsychological test of visual attention and task switching. It requires a subject to connect a sequence of 25 consecutive targets on a sheet of paper or computer screen. There are 2 parts to the test: in the first, the targets are all numbers from 1 to 25 and the test taker needs to connect them in sequential order; in the second part, the dots go from 1 to 13 and include letters from A to L. As in the first part, the patient must connect the dots in order while alternating letters and numbers, as in 1-A-2-B-3-C..., in the shortest time possible without lifting the pen from the paper. If the subject makes an error, the administrator corrects them before moving on to the next dot. The subject's goal is to finish both parts as quickly as possible, with the time taken to complete the test being used as the primary performance metric. Scoring is based on time taken to complete the test (e.g. 35 seconds yielding a score of 35) with lower scores being better
Time frame: Baseline and study week 10
Changes in Digit Symbol Test
This will be performed in a quiet exam room. Participants will have the opportunity to take breaks as needed and snacks will be provided. The Digit Symbol Substitution Test (DSST) is a paper-and-pencil cognitive test presented on a single sheet of paper that requires a subject to match symbols to numbers according to a key located on the top of the page. The subject copies the symbol into spaces below a row of numbers. The number of correct symbols within the allowed time, usually 90 to 120 seconds, constitutes the score.
Time frame: Baseline and study week 10
Changes in Letter Number Sequencing Test
This will be performed in a quiet exam room. Participants will have the opportunity to take breaks as needed and snacks will be provided. Letter-number sequencing is a subtest of the WAIS (Wechsler Adult Intelligence Scale) and the WISC (Wechsler Intelligence Scale for Children). It is a test that measures an individual's short-term memory skills in being able to process and re-sequence information. The task involves hearing a series of letters and digits, and then reporting back the stimuli with the letters in alphabetical order, and digits in ascending numerical order. The task is traditionally administered orally, but recent studies have administered versions of the tasks visually by displaying stimuli on a computer screen. Results suggest that performance differences on the Letter-Number Sequencing task may arise as a function of language background and task administration modality
Time frame: Baseline and study week 10
Changes in Wisconsin Card Sorting Test
This will be performed in a quiet exam room. Participants will have the opportunity to take breaks as needed and snacks will be provided.
Time frame: Baseline and study week 10
Changes in Grooved Pegboard Test
This will be performed in a quiet exam room. Participants will have the opportunity to take breaks as needed and snacks will be provided. The Grooved Pegboard Test (GPT) is used primarily as a measure of motor functioning, but some research indicates that performance on this test my also reflect cognitive factors, particularly attention and executive functioning. This manipulative dexterity test contains twenty-five holes with randomly positioned slots and pegs which have a key along one side. Pegs must be rotated to match the hole before they can be inserted. This procedure measures performance speed in a fine motor task by examining both sides of the body, inferences may be drawn regarding possible lateral brain damage. The test requires more complete visual motor coordination than most of our pegboards and has been used in several neuropsychological test batteries, in student labs, and as a screening technique in industrial environment.
Time frame: Baseline and study week 10
Changes in Letter and category fluency test
This will be performed in a quiet exam room. Participants will have the opportunity to take breaks as needed and snacks will be provided.
Time frame: Baseline and study week 10
Changes in Beck Depression Inventory II (BDI-II)
This will be performed in a quiet exam room. Participants will have the opportunity to take breaks as needed and snacks will be provided. The BDI-II is a widely used 21-item self-report inventory measuring the severity of depression in adolescents and adults. The questionnaire consists of 21 questions with answers ranging from 0 to 3. Scores are later analyzed by adding all scores and comparing to ranges : 0-10:These ups and downs are considered normal 11-16:Mild mood disturbance 17-20:Borderline clinical depression 21-30:Moderate depression 31-40: Severe depression over 4: Extreme depression
Time frame: Baseline and study week 10
Changes in MRI neuroimaging findings
Brain structure and function will be evaluated using magnetic resonance (MR) data acquired on a 7T Siemens Terra scanner with a multi-channel head coil. Data acquisition will include sequences for structural imaging, resting state functional MRI, diffusion imaging, perfusion imaging, and magnetic resonance spectroscopy.
Time frame: Baseline and study week 10
Plan to share: Yes — Medical and social history, laboratory results, imaging results, neuropsychological test results
Supporting information: Study protocol, Sap
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