I have not seen this posted anywhere earlier.
Highlights from the Tenth International Workshop on HIV Persistence during Therapy, December 13-16, 2022, Miami, Florida-USA
"began with a presentation from
Jonah Sacha (Oregon Health and Science University) who discussed the role of CCR5 in HIV prevention and cure.
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CCR5 is the major co-receptor for HIV/SIV entry and reports of HIV cure
in people with HIV who had received hematopoietic stem cell
transplantation (HSCT) from CCR5delta32 donors to treat malignancies
suggest that targeting CCR5 may be an effective strategy to eliminate
HIV persistence."
"
Gabriela Webb from the Oregon Health and Science
University next discussed CCR5 blockade as a scalable
non-transplantation approach for long-term ART-free HIV remission.
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She sought to mimic the CCR5Δ32/Δ32 phenotype by using the
CCR5-blocking IgG4 monoclonal antibody leronlimab and test if AAV9 could
induce long-term expression in SHIV-infected macaques. Webb discussed
two proof-of-concept cases of long-term transgene expression and
suppressed viremia. In case #1 the macaque received AAV9 human
leronlimab, dexamethasone and tacrolimus to limit immune activation.
This animal reached 100% CCR5 receptor occupancy on CD4
+T
cells, possessed detectable plasma leronlimab with no antidrug
antibodies (ADA). SHIV viremia became undetectable at 4 weeks until 33
weeks. In case #2, the macaque received AAV9 macaque leronlimab with no
immune suppression. 100% CCR5 receptor occupancy was reached and plasma
leronlimab was detected within 2 weeks. ADA developed at 4 weeks
post-AAV, but then resolved. SHIV viremia became undetectable shortly
after resolution of ADA.
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This demonstrates the potential of AAV vectors for sustained
antibody-based CCR5 blockade as a gene therapy approach for long-term
ART-free HIV remission. Future studies will aim to reduce ADA, increase
leronlimab expression, and test alternate AAV capsids."
