The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Persistent controllers (PCs) achieve indefinite antiretroviral-free HIV-1 control.
• Transient controllers (TCs) eventually lose virological control.
• Understanding HIV reservoir quality is key to preventing progression and finding a cure.

Purpose of the Study:

• To characterize the HIV-1 reservoir in persistent and transient controllers.
• To identify factors contributing to HIV progression and inform cure strategies.

Main Methods:

• Peripheral blood mononuclear cells were analyzed using next-generation sequencing.
• Full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq) were employed.

Main Results:

• PCs and TCs had lower total, intact, and defective proviruses than those on ART.
• Intact provirus levels were lower in PCs than TCs, with a higher intact/defective ratio in TCs.
• Clonally expanded intact proviruses in PCs were in heterochromatic regions; in TCs, they were in euchromatic positions.

Conclusions:

• Distinct proviral landscapes may be associated with persistent HIV-1 control without ART.
• These findings guide future research into the mechanisms of sustained HIV control.
• Identifying these distinct features is crucial for developing novel HIV cure interventions.