# Howard University Research Center for Minority Health and Health Disparities

> **NIH NIH U54** · HOWARD UNIVERSITY · 2021 · $386,250

## Abstract

Project Summary/Abstract
Highly active combination antiretroviral therapy (cART) has revolutionized the treatment of HIV/AIDS. However,
cART must be maintained for life, as HIV-1 continues to replicate in anatomical and cellular reservoirs for the
lifetime of the individuals receiving cART. Cellular and anatomical reservoirs of HIV-1 represent major
impediments to eradication. Lymphoid tissues (i.e. lymph nodes (LN), spleen, gut associated lymphoid tissues
(GALT), among others) harbor most of the body’s CD4+ T cells. Replication competent HIV-1 persists in
reservoirs throughout the body despite seemingly effective suppressive cART, with viral recrudescence
inevitably occurring when cART is halted. HIV-1 cure research aims at removal of HIV-1 provirus from latent
cells and targeting cARVs to HIV-1 reservoirs. The main challenge in all cure strategies lies in inefficient delivery
of the therapeutic agents to viral reservoirs. Many cART drugs and latency reversing agents (LRAs) differ in
solubility, bioavailability, and toxicity which make dosing and formulation very challenging to deliver
physicochemically diverse cure agents simultaneously. Nanotechnology has emerged as a promising approach
for HIV cure due to several key attributes: ability to encapsulate diverse agents, increased circulation or tissue
retention time, sustained drug release, enhanced solubility and bioavailability, reduced toxicity or side effects,
and enhanced drug potency. Some nanocarriers can also be modified to target specific cells or tissues. We
intend to harness the promising properties of nanoparticles to address problems in current novel
strategies toward HIV cure (LRAs combination for reactivating latently infected cells and administration
of cARVs to HIV reservoirs). HIV persists in lymph nodes during aggressive drug treatment. Targeting
nanoparticles to CD4+ T cells in the lymph node may provide site-specific delivery of drugs (cARVs and LRAs).
The spleen contains 25% of the body’s lymphocytes. Studies have shown that the spleen has a very high blood
flow; it is one of the most perfused organs in the body. We hypothesize the development of biodegradable
polymeric nanotechnological platforms using (A) CD4 binding peptide (CKGIRIGPGRAVYAAE) and separately
(B) CD4 binding monoclonal antibody (ibalizumab: FDA approved) which targets the extracellular CD4 domain
of CD4+ Tcells) as targeting moieties for delivery of targeted nanoparticle formulations (cARVs: cabotegravir
and rilpivirine and LRAs: vorinostat and chaetocin) to lymph nodes. Further, we hypothesize the
development of biodegradable polymeric nanotechnological platforms using (C) monoclonal antibody
rituximab, which targets splenic antigens (i.e., CD20 antigens on B cells and splenocytes) in the spleen and (D)
CD4 binding monoclonal antibody (ibalizumab) as targeting moieties for targeting nanoparticle to the spleen
(to target cARVs (cabotegravir and rilpivirine) and LRAs (vorinostat and chaetocin) to the spleen...

## Key facts

- **NIH application ID:** 10451992
- **Project number:** 3U54MD007597-33S4
- **Recipient organization:** HOWARD UNIVERSITY
- **Principal Investigator:** William M. Southerland
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $386,250
- **Award type:** 3
- **Project period:** 1997-09-30 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451992

## Citation

> US National Institutes of Health, RePORTER application 10451992, Howard University Research Center for Minority Health and Health Disparities (3U54MD007597-33S4). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10451992. Licensed CC0.

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