# High-Definition Characterization of the Persistence and Perturbation of the HIV Reservoir: Project 2

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $513,513

## Abstract

Abstract
A considerable number of clinical, neuropathological, immunohistochemical and immunological studies suggest
that human brain cells, in particular those of myeloid origin, are susceptible to HIV-1; infection of these cells may
contribute to neurocognitive dysfunction and viral long-term persistence despite ART. However, among all
anatomical tissue locations in the human body, the central nervous system (CNS) arguably represents the most
difficult one to access and to evaluate for viral infection and persistence. Recently, significant progress has been
made in defining viral reservoirs using novel next-generation sequencing approaches, frequently allowing viral
sequence profiling at single-genome or single-cell resolution. Using such technologies, it is possible to profile
the evolutionary dynamics of viral species in the CNS in great detail, and to obtain rare insight into the underlying
mechanisms and pathways that influence HIV-1 reservoir establishment and persistence in the CNS. Here, we
propose a collaborative, interdisciplinary research project involving investigators with complementary experience
in neurology, neuropathology, virology, computational modeling and clinical care of HIV-1 patients to advance
the current understanding of the CNS as an anatomical site for long-term persistence of replication-competent
HIV-1. In specific aim 1, we will leverage a unique collection of paired CSF and plasma samples from
longitudinally-followed, untreated HIV-1 patients to evaluate phylogenetic associations and interrelated viral
population genomics between viral sequences from the CNS and alternative anatomical compartments; these
studies will be instrumental for tracking the seeding and establishment of long-lasting viral reservoirs pre-ART.
In specific aim 2, we will use autopsy material from ART-treated HIV-1 patients with suppressed viremia at death
to profile the frequency, clonality, chromosomal location and replication competence of proviruses isolated from
sorted CNS cells, in particular from myeloid parenchymal microglia, from myeloid perivascular macrophages and
astrocytes. Together, these studies will allow for a deep characterization of HIV-1 reservoir cell dynamics in the
CNS, and may be informative for future clinical strategies aiming at HIV-1 eradication and cure.

## Key facts

- **NIH application ID:** 10469112
- **Project number:** 1P01AI169768-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Mathias Lichterfeld
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $513,513
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469112

## Citation

> US National Institutes of Health, RePORTER application 10469112, High-Definition Characterization of the Persistence and Perturbation of the HIV Reservoir: Project 2 (1P01AI169768-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10469112. Licensed CC0.

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