# HIV-1 EnvLRS: a scalable, sequence-based assay for in-depth assessment of HIV-1 bNAb resistance

> **NIH NIH R43** · ACCELEVIR DIAGNOSTICS, LLC · 2021 · $300,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 Human immunodeficiency virus type-1 (HIV-1) is a retrovirus that infects CD4+ T cells of the immune
system. If left untreated, people living with HIV-1 (PLWH) will progress to AIDS and may ultimately die as a
result. Combination antiretroviral therapy (ART) with small-molecule drugs is extremely effective at stopping
the replication of HIV-1 in infected individuals but requires daily dosing often with considerable side effects.
Importantly, despite the success of this approach at suppressing HIV-1 replication to clinically undetectable
levels, antiretroviral therapy is not curative. This is due to the persistence of HIV-1 in a silent, or latent, state
within long-lived CD4+ T cells at extremely low frequencies. These latently infected cells are not targeted by
current small-molecule ART regimens. As a result, PLWH must remain on lifelong antiretroviral therapy.
 Broadly neutralizing antibodies targeting critical epitopes in HIV-1 Env (HIV-1 bNAbs) are currently
being developed as a potential approach to eliminate latent HIV-1 and/or as an alternative to small-molecule
ART. HIV-1 bNAbs offer several advantages over traditional small-molecule ART, including the potential for
long-acting formulations, reduced side effects, and the potential to eliminate latently infected cells over time.
However, a major challenge to the implementation of HIV-1 bNAbs in treatment and cure is pre-existing
variation or resistance in the bNAb-targeted epitopes. Scalable clinical tests are needed to determine (1)
whether people who will receive HIV-1 bNAbs have pre-existing resistance, and (2) personalize HIV-1 bNAb
combinations to each individual. To address this critical unmet need, AccelevirDx is developing the HIV-1
EnvLRS assay as the first scalable sequence-based test to assess HIV-1 bNAb resistance and predict
antibody efficacy by in-depth env sequence analysis. Broadly, this proposal aims to (1) analytically qualify
AccelevirDx’s novel, proprietary HiFi-dePCR approach for env amplification underlying HIV-1 EnvLRS, (2)
determine the reproducibility of the HIV-1 EnvLRS assay of samples from PLWH, and (3) apply the assay to a
recently completed ACTG A5340 clinical trial of the HIV-1 bNAb VRC01 in PLWH to assess assay
performance and utility.

## Key facts

- **NIH application ID:** 10324540
- **Project number:** 1R43AI165126-01
- **Recipient organization:** ACCELEVIR DIAGNOSTICS, LLC
- **Principal Investigator:** Gregory Michael Laird
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2021-07-23 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10324540

## Citation

> US National Institutes of Health, RePORTER application 10324540, HIV-1 EnvLRS: a scalable, sequence-based assay for in-depth assessment of HIV-1 bNAb resistance (1R43AI165126-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10324540. Licensed CC0.

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