# Monocyte Traffic and Neuropathogenesis of AIDS

> **NIH NIH R01** · BOSTON COLLEGE · 2021 · $699,282

## Abstract

Project Abstract
HAND HIV-associated neurocognitive disorders (HAND) including asymptomatic neurocognitive impairment
(ANI), mild neurocognitive disorders (MND) and HIV-associated dementia (HAD) persist despite effective
antiretroviral therapy (ART). HAD is markedly decreased but ANI and MND persist and affecting 25-50% of
ART-treated individuals. With durable ART, there is emergent evidence of chronic immune system activation
that contributes to AIDS-related co-morbidities including HAND and cardiovascular disease (CVD). Chronic
immune activation that includes activated monocyte/macrophages and markers on these cells are consistently
associated with these comorbidities. While the mechanisms for chronic immune activation with HIV and ART
aren’t well understood, microbial translocation, secondary infections and residual viral replication in cell and
tissue reservoirs likely play a role. Central to all these mechanisms is activated monocyte/macrophages. In
addition to memory CD4+ T cells, macrophages are cellular reservoirs for latent HIV, and the central nervous
system (CNS) is a tissue reservoir for HIV- DNA. Thus, there is a great need for adjunctive therapies to be
used with cART that target monocyte/macrophage activation, accumulation in parenchymal tissues
and latent-replication competent virus. In this proposal we use a rapid AIDS with ART that does not
results in encephalitis with 1) methylglyoxal bis(guanylhydrazone) (MGBG) and 2) a rhesus monkey
(Rh) anti-41 integrin mAb, as adjunctive therapies targeting activated and infected
monocyte/macrophages. Extending findings from our previous funding period, we propose these two
approaches; targeting monocyte/macrophage activation and maturation, accumulation in the CNS and blocking
SIVE. We propose to define mechanisms by which these adjunctive therapies function. Moreover, we
propose to test the ability of MGBG and anti-41 integrin mAb with ART to clear latent, replication competent
virus within macrophages within and leaving the CNS, following therapy interruption.

## Key facts

- **NIH application ID:** 10073553
- **Project number:** 5R01NS040237-20
- **Recipient organization:** BOSTON COLLEGE
- **Principal Investigator:** KENNETH C WILLIAMS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $699,282
- **Award type:** 5
- **Project period:** 1999-09-30 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073553

## Citation

> US National Institutes of Health, RePORTER application 10073553, Monocyte Traffic and Neuropathogenesis of AIDS (5R01NS040237-20). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10073553. Licensed CC0.

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