Interferon-associated therapies toward HIV control: The back and forth.

Area of Science:

• Immunology
• Virology
• Therapeutics

Background:

• Human Immunodeficiency Virus (HIV) infection is persistent and incurable, though combined antiretroviral treatment (cART) manages it as a chronic condition.
• HIV eradication from cellular and anatomical reservoirs is crucial for achieving a cure, driving research into novel therapies.
• Type I Interferon (IFN-I) possesses antiviral properties, leading to its investigation in early HIV treatment before effective cART development.

Purpose of the Study:

• To review the historical use of IFN-I in HIV therapy, its limitations, and lessons learned.
• To explore the renewed interest in IFN-I as a potential component of HIV cure strategies in the context of cART.
• To examine novel therapeutic approaches involving IFN-I, including combinations with cART and strategies to enhance IFN-I function or counteract excessive IFN pathway activation.

Main Methods:

• Historical review of IFN-based therapeutic strategies for HIV.
• Analysis of factors influencing IFN-I efficacy, such as timing and patient context (e.g., endogenous IFN-signature).
• Evaluation of current research on novel IFN-I-based therapies in combination with cART and alternative IFN subtypes.

Main Results:

• Early IFN-based strategies had limitations, with efficacy dependent on administration timing and patient's IFN-signature.
• Current trials combining IFN-I with cART show mixed results, with some encouraging reductions in HIV reservoir size and delays in viral rebound.
• Development of strategies to improve IFN-I antiviral function and modulate IFN pathways is ongoing.

Conclusions:

• Lessons from past IFN-I trials inform current research for HIV cure strategies.
• Novel combinations of IFN-I with cART and enhanced IFN-I modulation hold potential for reducing HIV reservoirs and achieving functional cures.
• Continued research into optimized IFN-I-based therapies is essential for advancing HIV treatment.