# Phase II study to evaluate the efficacy and safety of baricitinib for reduction of HIV in the central nervous system

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $638,381

## Abstract

Project Summary/Abstract
 Although HIV infection is controllable with antiretroviral therapy (ART), HIV cure continues to be
extremely elusive. Cure of HIV is desperately needed for many reasons. People with HIV (PWH) have persistent
increases in morbidity and mortality despite ART, and while newer ART agents have become better tolerated,
they are still associated with multiple side effects. Having to attend HIV clinics and take ART over the long term
still carries significant stigma for PWH. Additionally, many PWH have a preference for cure rather than a lifetime
of ART, and some would take significant risks to achieve a cure. For all of these reasons, finding a cure for HIV
is one of the ultimate goals of the field.
 There is a large and growing body of evidence that the central nervous system (CNS) is an HIV reservoir
site that represents another barrier to HIV eradication. HIV DNA is commonly found in brain tissue from PWH on
suppressive ART, and there are multiple published reports of CNS virologic escape. Multiple studies, including
from our group, have demonstrated that HIV RNA can be detected at very low levels in CSF during suppressive
ART and that anti-HIV antibodies are also present in the CSF among individuals on ART. New members of our
group recently presented findings with an innovative assay (Double-R) to reliably quantitate HIV RNA and DNA
from CSF.
 Our group has performed extensive pre-clinical and clinical work on the Janus Kinase (Jak 1/2) inhibitor
drug class to target HIV. This includes work on baricitinib, an FDA approved orally bioavailable Jak 1/2 inhibitor
for rheumatoid arthritis. We have demonstrated that baricitinb blocks HIV replication, HIV-induced activation and
infection in key CNS cells, and reservoir reseeding. In vivo, we have shown in our murine model that baricitinib
decreases CNS HIV and reverses behavioral abnormalities conferred by HIV. We have also demonstrated that
baricitinib achieves therapeutic CNS concentrations in the rhesus macaque model. We now propose to study
baricitinib as a therapy to decrease the HIV CNS reservoir in a study of PWH with durable virologic suppression
on ART. This will be a phase IIa randomized placebo controlled study. Our primary hypothesis is that individuals
randomized to baricitinib will be more likely to achieve a decrease in CSF cell associated HIV RNA and DNA by
Double-R assay. We also hypothesize that baricitinib treatment will be associated with a significant decrease in
other markers of HIV CNS persistence, including HIV-specific CSF antibodies, CSF cell associated DNA
including by Integrated Proviral DNA (IPDA), CSF RNA by single copy assay, CSF HIV Tat levels, and markers
of inflammation that have been linked to CNS HIV persistence, as well as magnetic resonance imaging and
spectroscopy markers. Additionally, we hypothesize that baricitinib treatment will be safe for the CNS as defined
by neuropsychological performance, depression symptoms, and neuronal damage. We ...

## Key facts

- **NIH application ID:** 10484645
- **Project number:** 1R01MH128158-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Albert Anderson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $638,381
- **Award type:** 1
- **Project period:** 2022-08-10 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10484645

## Citation

> US National Institutes of Health, RePORTER application 10484645, Phase II study to evaluate the efficacy and safety of baricitinib for reduction of HIV in the central nervous system (1R01MH128158-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10484645. Licensed CC0.

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