Correlates of HIV-1 control after combination immunotherapy

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Achieving sustained, treatment-free control of HIV infection is a critical research goal.
• Combination immunotherapy strategies, including vaccination and broadly neutralizing antibodies (bNAbs), show promise in preclinical models but require human translation.

Purpose of the Study:

• To evaluate a combination immunotherapy approach in people living with HIV (PLWH).
• To assess the feasibility and efficacy of a multi-pronged strategy involving therapeutic vaccination, bNAbs, and immune stimulation for ART-free HIV control.

Main Methods:

• A single-arm, proof-of-concept study involving ten participants on antiretroviral therapy (ART).
• The intervention included therapeutic vaccination (HIV/Gag CE-targeted DNA+IL-12 prime/MVA boost), administration of two bNAbs (10-1074, VRC07-523LS) with a toll-like receptor 9 agonist (lefitolimod) during ART, followed by repeat bNAb dosing upon ART interruption.
• Monitoring of viral load and immune responses, particularly CD8+ T cell activation, post-ART cessation.

Main Results:

• Seven of ten participants achieved post-intervention control of HIV after stopping ART, independent of circulating bNAb levels.
• A strong correlation was observed between the early expansion of activated CD8+ T cells in response to viral rebound and lower viral loads off ART.
• The combination immunotherapy approach demonstrated potential in facilitating sustained HIV control.

Conclusions:

• Combination immunotherapy, integrating therapeutic vaccination and bNAbs, may offer a viable strategy for inducing sustained ART-free HIV control.
• Enhancing CD8+ T cell responses appears crucial for managing viral rebound and achieving long-term remission.
• Further optimization of these immunotherapy combinations is warranted to improve efficacy in PLWH.