Research offers clues for potential widespread HIV cure in people
New study reveals first details on how stem cell transplantation can kill virus that causes AIDS

Date:
May 25, 2023
Source:
Oregon Health & Science University
Summary:
New animal research is helping explain why at least five people
have become HIV-free after receiving a stem cell transplant,
and may bring scientists closer to developing what they hope will
be a widespread cure for the virus that causes AIDS. A new study
describes how two nonhuman primates were cured of the monkey form
of HIV after receiving a stem cell transplant. It also reveals that
two circumstances must co-exist for a cure to occur and documents
the order in which HIV is cleared from the body.


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FULL STORY ==========================================================================
New research from Oregon Health & Science University is helping explain
why at least five people have become HIV-free after receiving a stem
cell transplant.

The study's insights may bring scientists closer to developing what
they hope will become a widespread cure for the virus that causes AIDS,
which has infected about 38 million people worldwide.

Published today in the journal Immunity, the OHSU-led study describes
how two nonhuman primates were cured of the monkey form of HIV after
receiving a stem cell transplant. It also reveals that two circumstances
must co-exist for a cure to occur and documents the order in which HIV
is cleared from the body - - details that can inform efforts to make
this cure applicable to more people.

"Five patients have already demonstrated that HIV can be cured," said the study's lead researcher, Jonah Sacha, Ph.D., a professor at OHSU's Oregon National Primate Research Center and Vaccine and Gene Therapy Institute.

"This study is helping us home in on the mechanisms involved in making
that cure happen," Sacha continued. "We hope our discoveries will help to
make this cure work for anyone, and ideally through a single injection
instead of a stem cell transplant." The first known case of HIV being
cured through a stem cell transplant was reported in 2009. A man who was
living with HIV was also diagnosed with acute myeloid leukemia, a type of cancer, and underwent a stem cell transplant in Berlin, Germany. Stem
cell transplants, which are also called bone marrow transplants,
are used to treat some forms of cancer. Known as the Berlin patient,
he received donated stem cells from someone with a mutated CCR5 gene,
which normally codes for a receptor on the surface of white blood cells
that HIV uses to infect new cells. A CCR5 mutation makes it difficult for
the virus to infect cells, and can make people resistant to HIV. Since
the Berlin patient, four more people have been similarly cured.

This study was conducted with a species of nonhuman primate known
as Mauritian cynomolgus macaques, which the research team previously demonstrated can successfully receive stem cell transplants. While all of
the study's eight subjects had HIV, four of them underwent a transplant
with stem cells from HIV- negative donors, and the other half served as
the study's controls and went without transplants.

Of the four that received transplants, two were cured of HIV after
successfully being treated for graft-versus-host disease, which is
commonly associated with stem cell transplants.

Other researchers have tried to cure nonhuman primates of HIV using
similar methods, but this study marks the first time that HIV-cured
research animals have survived long term. Both remain alive and HIV-free
today, about four years after transplantation. Sacha attributes their
survival to exceptional care from Oregon National Primate Research Center veterinarians and the support of two study coauthors, OHSU clinicians who
care for people who undergo stem cell transplants: Richard T. Maziarz,
M.D., and Gabrielle Meyers, M.D.

"These results highlight the power of linking human clinical studies
with pre- clinical macaque experiments to answer questions that would be
almost impossible to do otherwise, as well as demonstrate a path forward
to curing human disease," said Maziarz, a professor of medicine in the
OHSU School of Medicine and medical director of the adult blood and
marrow stem cell transplant and cellular therapy programs in the OHSU
Knight Cancer Institute.

The how behind the cure Although Sacha said it was gratifying to confirm
stem cell transplantation cured the nonhuman primates, he and his fellow scientists also wanted to understand how it worked. While evaluating
samples from the subjects, the scientists determined there were two
different, but equally important, ways they beat HIV.

First, the transplanted donor stem cells helped kill the recipients' HIV- infected cells by recognizing them as foreign invaders and attacking
them, similar to the process of graft-versus-leukemia that can cure
people of cancer.

Second, in the two subjects that were not cured, the virus managed to jump
into the transplanted donor cells. A subsequent experiment verified that
HIV was able to infect the donor cells while they were attacking HIV. This
led the researchers to determine that stopping HIV from using the CCR5
receptor to infect donor cells is also needed for a cure to occur.

The researchers also discovered that HIV was cleared from the subjects'
bodies in a series of steps. First, the scientists saw that HIV was no
longer detectable in blood circulating in their arms and legs. Next,
they couldn't find HIV in lymph nodes, or lumps of immune tissue that
contain white blood cells and fight infection. Lymph nodes in the limbs
were the first to be HIV- free, followed by lymph nodes in the abdomen.

The step-wise fashion by which the scientists observed HIV being cleared
could help physicians as they evaluate the effectiveness of potential HIV cures. For example, clinicians could focus on analyzing blood collected
from both peripheral veins and lymph nodes. This knowledge may also help explain why some patients who have received transplants initially have
appeared to be cured, but HIV was later detected. Sacha hypothesizes that
those patients may have had a small reservoir of HIV in their abdominal
lymph nodes that enabled the virus to persist and spread again throughout
the body.

Sacha and colleagues continue to study the two nonhuman primates cured
of HIV.

Next, they plan to dig deeper into their immune responses, including identifying all of the specific immune cells involved and which specific
cells or molecules were targeted by the immune system.

This research is supported by the National Institutes of Health (grants AI112433, AI129703, P51 OD011092) and the Foundation for AIDS Research
(grant 108832), and the Foundation for AIDS Immune Research. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.

In our interest of ensuring the integrity of our research and as part of
our commitment to public transparency, OHSU actively regulates, tracks
and manages relationships that our researchers may hold with entities
outside of OHSU. In regard to this research, Dr. Sacha has a significant financial interest in CytoDyn, a company that may have a commercial
interest in the results of this research and technology. Review?details
of OHSU's conflict of interest program?to find out more about how we
manage these business relationships.

All research involving animal subjects at OHSU must be reviewed and
approved by the university's?Institutional Animal Care and Use Committee (IACUC). The IACUC's priority is to ensure the health and safety of
animal research subjects. The IACUC also reviews procedures to ensure
the health and safety of the people who work with the animals. No live
animal work may be conducted at OHSU without IACUC approval.

REFERENCE: Helen Wu, Kathleen Busman-Sahay, Whitney C. Weber, Courtney M.

Waytashek, Carla D. Boyle, Katherine Bateman, Jason S. Reed, Joseph
M. Hwang, Christine Shriver-Munsch, Tonya Swanson, Mina Northrup,
Kimberly Armantrout, Heidi Price, Mitch Robertson-LeVay, Samantha Uttke,
Mithra R. Kumar, Emily J.

Fray, Sol Taylor-Brill, Stephen Bondoc, Rebecca Agnor, Stephanie
L. Junell, Alfred W. Legasse, Cassandra Moats, Rachele M. Bochart,
Joseph Sciurba, Benjamin N. Bimber, Michelle N. Sullivan, Brandy Dozier,
Rhonda P. MacAllister, Theodore R. Hobbs, Lauren D. Martin, Angela Panoskaltsis-Mortari, Lois M.A.

Colgin, Robert F. Silciano, Janet D. Silciano, Jacob D. Estes, Jeremy V.

Smedly, Michael K. Axthelm, Gabrielle Meyers, Richard T. Maziarz,
Benjamin J.

Burwitz, Jeffrey J. Stanton, Jonah B. Sacha, Allogeneic immunity clears
latent virus following allogenic stem cell transplantation in SIV-infected antiretroviral therapy-suppressed macaques, Immunity, May 25, 2023,
DOI: 10.1016/j.immuni.2023.04.019.

* RELATED_TOPICS
o Health_&_Medicine
# HIV_and_AIDS # Stem_Cells # Infectious_Diseases #
Lymphoma
o Plants_&_Animals
# Mice # Biotechnology # Biology #
Biotechnology_and_Bioengineering
* RELATED_TERMS
o AIDS o HIV_test o Stem_cell o Adult_stem_cell o
Embryonic_stem_cell o Stem_cell_treatments o Antiretroviral_drug
o Somatic_cell_nuclear_transfer

========================================================================== Story Source: Materials provided by
Oregon_Health_&_Science_University. Original written by Franny
White. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Helen L. Wu, Kathleen Busman-Sahay, Whitney C. Weber, Courtney M.

Waytashek, Carla D. Boyle, Katherine B. Bateman, Jason S. Reed,
Joseph M.

Hwang, Christine Shriver-Munsch, Tonya Swanson, Mina Northrup,
Kimberly Armantrout, Heidi Price, Mitch Robertson-LeVay, Samantha
Uttke, Mithra R.

Kumar, Emily J. Fray, Sol Taylor-Brill, Stephen Bondoc, Rebecca
Agnor, Stephanie L. Junell, Alfred W. Legasse, Cassandra Moats,
Rachele M.

Bochart, Joseph Sciurba, Benjamin N. Bimber, Michelle N. Sullivan,
Brandy Dozier, Rhonda P. MacAllister, Theodore R. Hobbs, Lauren
D. Martin, Angela Panoskaltsis-Mortari, Lois M.A. Colgin, Robert
F. Siliciano, Janet D. Siliciano, Jacob D. Estes, Jeremy V. Smedley,
Michael K. Axthelm, Gabrielle Meyers, Richard T. Maziarz, Benjamin
J. Burwitz, Jeffrey J.

Stanton, Jonah B. Sacha. Allogeneic immunity clears latent
virus following allogeneic stem cell transplantation in
SIV-infected ART- suppressed macaques. Immunity, 2023; DOI:
10.1016/j.immuni.2023.04.019 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/05/230525141517.htm

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