Autologous neutralizing antibodies and polyfunctional T cells contribute to long-term HIV-1 post-intervention control

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Antiretroviral therapy (ART) interruption typically causes rapid HIV-1 viral rebound.
• Developing an HIV-1 cure requires understanding immune mechanisms that prevent viral rebound.

Purpose of the Study:

• To investigate immunological factors enabling long-term ART-free HIV-1 control in exceptional individuals.
• To characterize the proviral reservoir and immune responses in post-intervention controllers (PICs).

Main Methods:

• Described three PICs maintaining ART-free virological control after broadly neutralizing antibody administration.
• Quantified genetically intact/inducible proviral reservoirs.
• Assessed autologous neutralizing antibodies and HIV-1-specific CD4+ and CD8+ T cell responses.

Main Results:

• PICs maintained ART-free control for >6.5, >7.5, and 2.5 years.
• Proviral reservoirs were increasingly clonal and located in nongenic/centromeric regions, suggesting immune selection.
• Potent neutralizing antibodies and polyfunctional T cell responses persisted during ART interruption.
• Viral rebound in one PIC correlated with mutations escaping immune responses.

Conclusions:

• Exceptional immune responses, including neutralizing antibodies and T cells, are crucial for ART-free HIV-1 control.
• Immune-mediated selection shapes the proviral reservoir.
• Enhancing pre-existing adaptive immunity is a promising HIV-1 curative strategy.