HIV-Specific Adoptive T Cell Therapy to Target Viral Reservoirs

Development of a tissue- and virus-specific cellular immune therapy to control HIV infections

The Problem
Anti-retroviral therapy (ART) to suppress HIV requires lifelong treatment that can have side effects that create a burden for the patient.
The Solution
This project examines treatment regimens involving engineered T cells to target and reduce the abundance of residual virus-infected cells to control virus replication in the absence of anti-retroviral therapy.

Overview

Anti-retroviral therapy (ART) is highly effective in reducing HIV present in the bloodstream of HIV-positive individuals to undetectable levels and preventing virus transmission to uninfected sexual partners. However, patients need to take ART every day for the rest of their lives; as soon as ART is stopped or interrupted, high levels of HIV in the bloodstream are quickly reestablished.

Evidence suggests that persistent viral infection of a subset of CD4 T cells contributes to an overall viral reservoir in HIV-positive individuals. This project leverages a similarity between the viral reservoir in humans with HIV and in monkeys infected with simian immunodeficiency virus (SIV)—the equivalent of HIV in nonhuman primates—to test a new approach to control virus levels over the long term. This project will examine the ability of engineered killer T cells to locate to particular tissues and specifically target and clear SIV-infected cells. In addition, this project will explore whether immune-modulating signals can be used to enhance antiviral activity in areas where immune activity is normally highly restricted. The project aims to demonstrate a proof-of-concept for therapeutic treatment regimen of HIV infection that may lessen or reduce the need for lifelong treatments.

Public-Sector Partner

Contact

David Brown, Scientific Program Manager, dbrown@fnih.org
Rebeca Salmeron, Project Manager, rsalmeron@fnih.org

Goals

Develop a more definitive treatment of HIV infection that may lessen the burden of lifelong treatment

Results & Accomplishments

Leidos received the project award and initiated research efforts in September 2020. The project is now in early stages of testing the primary hypothesis.