Advances toward a cure for HIV: getting beyond n=2.

Area of Science:

• Virology
• Immunology
• Gene Therapy

Background:

• HIV cure remains a significant challenge in medical research.
• Two cases of 'sterilizing cure' achieved via CCR5-delta 32 deletion hematopoietic stem cell transplantation (HSCT) offer hope.
• Various strategies are being explored for sterilizing or functional HIV cure.

Purpose of the Study:

• To summarize current HIV cure research strategies.
• To discuss the role of CCR5 in HIV infection and potential therapeutic targets.
• To review advancements presented at the International Antiviral Society-USA (IAS-USA) continuing education program.

Main Methods:

• Review of existing HIV cure strategies, including HSCT, early antiretroviral therapy (ART), and 'shock and kill' approaches.
• Analysis of gene therapy techniques targeting CCR5, HIV proviruses, or T cells.
• Summary of a presentation by Jonathan Li, MD, MMSc.

Main Results:

• Allogeneic HSCT from CCR5-delta 32 homozygous donors has led to sterilizing HIV cure in select cases.
• Early ART initiation may limit the size of the HIV latent reservoir.
• Novel gene therapies and 'shock and kill' methods are under active investigation.

Conclusions:

• Hematopoietic stem cell transplantation targeting CCR5 is a validated, albeit high-risk, strategy for HIV cure.
• A multi-pronged approach combining various therapeutic modalities may be necessary for a widespread HIV cure.
• Continued research into latency reversal, gene editing, and immune-based therapies is crucial for advancing HIV cure efforts.