No recovery of replication-competent HIV-1 from human liver macrophages

Area of Science:

• Immunology
• Virology
• Hepatology

Background:

• Persistent human immunodeficiency virus type 1 (HIV-1) reservoirs, despite antiretroviral therapy (ART), hinder efforts toward an HIV-1 cure.
• Human liver macrophages (LMs) represent the largest tissue macrophage population, prompting investigation into their role as a potential HIV-1 reservoir.

Purpose of the Study:

• To determine if human liver macrophages (LMs) constitute a persistent reservoir for HIV-1.
• To assess the viral propagation capacity of HIV-1 residing within LMs during ART.

Main Methods:

• Purification of LMs from liver explants of HIV-1-infected individuals, including those on long-term ART.
• Ex vivo stimulation of purified LMs to assess viral release and propagation.
• In vitro experiments to quantify the decay kinetics and viral release from HIV-1-infected LMs.

Main Results:

• HIV-1 transmission was observed from LMs of 6 out of 8 individuals on ART, but sustained propagation was limited.
• Sustained HIV-1 propagation from LMs was primarily observed in individuals on ART for less than one year.
• In vitro studies showed prolonged HIV-1-infected LM survival (>170 days) with detectable viral release, but with varying half-lives (3.8-55 days).

Conclusions:

• HIV-1 persists within human liver macrophages during ART.
• The HIV-1 within LMs appears largely inert or replication-defective, suggesting a restricted capacity for propagation.
• These findings indicate that LMs may represent a latent reservoir, potentially offering novel targets for HIV-1 eradication strategies.