and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.5 years after stopping ART,
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While alloHSCT is not a treatment suitable for widespread application, defining how this cure is achieved has profound implications for the future of the millions of people living with HIV (PLWH).
The following three potential mechanisms are hypothesized for how alloHSCT-mediated HIV cure in the four documented cases:
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Thus, a physiologically relevant, pre-clinical model of alloHSCT would provide unparalleled insight into the immunological processes that clear latent HIV and result in cure, thereby opening new avenues for non-alloHSCT therapeutic curative approaches.
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Our results define the individual contributions of allogeneic immunity and CCR5 deficiency to alloHSCT-mediated HIV cure and support the development of HIV curative modalities designed to mimic allogeneic immune responses without the need for the complex and dangerous process of alloHSCT.
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This would suggest that CCR5 deficiency is critically important in the peri-transplant period as lack of CCR5 on engrafting donor cells would shield them from infection while mediating allogeneic immunity via cell-to-cell contact.
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https://www.sciencedirect.com/science/article...1323002169