# Towards Suppression and Elimination of HIV in the CNS

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $680,675

## Abstract

PROJECT SUMMARY/ ABSTRACT
Despite the success of combined antiretroviral therapy (cART) to diminish peripheral infection,
HIV-1 can establish an infection in the central nervous system (CNS), resulting in the development
of cognitive, behavioral, and motor deficits associated with HIV-1 associated neurocognitive
disorders (HAND). Once infected, the CNS acts as a viral reservoir that is difficult to treat and
eradicate. Mononuclear phagocytes (MP, e.g., perivascular macrophages and microglia) are
important reservoirs in the immune-privileged CNS. The proposed studies are designed to
address the unique dynamics of HIV infection in CNS and explore novel therapeutic strategies
that target MP, ensure viable delivery across the blood-brain barrier (BBB) to eliminate the HIV
reservoir and reduce inflammation. HIV-induced activation and viral replication in MP are relevant
targets that that are the focus of our ongoing novel approaches through multiple pharmacological
agents. These approaches include design and development of: 1) MP-specific ribonucleoside
chain terminators (rNCTs) and their phosphate prodrugs, and 2) NADPH oxidase (NOX) inhibitors
that cross the BBB and target MP, and 3) JAK inhibitors that block/interrupt the activation state of
MP and can reduce inflammation. Selected therapeutic agents will be analyzed for their in vitro
antiviral potency, and to assess biochemistry, toxicology, and cellular pharmacology parameters.
We have recently identified low or sub-nanomolar MP-specific HIV inhibitors with a high
therapeutic index. These will be evaluated in vivo to assess CNS pharmacology and response
(including behavior and pathology) to treatment using two distinct retrovirus CNS animal models
we have previously established including SCID mouse model intracranially injected with HIV-1
infected MP, and macaque model infected with SIVmac239. Results from these studies will
identify new adjunctive therapeutic strategies which together with current cART should provide
improved targeted therapy to MP. The ultimate goal is to suppress virus and eliminate these HIV-
1 reservoirs in the CNS that should lead to improved treatments to reduce risk(s) of developing
HAND.

## Key facts

- **NIH application ID:** 10070650
- **Project number:** 5R01MH116695-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Raymond Felix Schinazi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $680,675
- **Award type:** 5
- **Project period:** 2018-03-10 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070650

## Citation

> US National Institutes of Health, RePORTER application 10070650, Towards Suppression and Elimination of HIV in the CNS (5R01MH116695-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10070650. Licensed CC0.

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