A woman in New York City has no detectable HIV 14 months after stopping antiretroviral therapy following a transplant of HIV-resistant stem cells, according to a presentation yesterday at the Conference on Retroviruses and Opportunistic Infections (CROI 2022) reports Aidsmap.com.
The woman, who received the stem cell transplant to treat leukaemia, is doing well, and both her cancer and HIV are in remission. While it is too soon to declare for certain that she is cured of HIV, experts are hopeful that the ‘New York patient’ will join the ‘Berlin patient’ and the ‘London patient’ as the third person to be free of HIV over the long term after stem cell transplantation. However, they caution that this is a risky procedure that is not applicable to most people living with the virus.
“This third case of an HIV cure post-bone marrow transplant from a donor naturally resistant to HIV, and the first in a woman living with HIV, is a very exciting finding,” said Professor Sharon Lewin, president-elect of the International AIDS Society. “A bone marrow transplant is not a viable large-scale strategy for curing HIV, but it does present a proof of concept that HIV can be cured.”
A new stem cell transplant approach
So far, only two people are widely regarded as cured of HIV, although some others with a shorter duration of follow-up may eventually join their ranks.
The first man to be cured, Timothy Ray Brown, formerly known as the Berlin patient, received two stem cell transplants to treat acute myeloid leukemia in 2006. The donor had two copies of a rare genetic mutation known as CCR5-delta-32, which leads to an absence of CCR5 co-receptors, the gateways most types of HIV use to enter T-cells.
Brown underwent intensive conditioning chemotherapy and radiotherapy to kill off his cancerous immune cells, allowing the donor stem cells to rebuild a new HIV-resistant immune system. But the donor immune cells attacked his native cells, resulting in severe graft-versus-host disease.
As described at CROI 2008, Brown stopped antiretroviral therapy at the time of his first transplant but his viral load did not rebound. Researchers extensively tested his blood, gut and other tissues, finding no evidence of replication-competent HIV anywhere in his body. At the time of his death in September 2020, due to a recurrence of leukaemia, Brown had been free of HIV for more than 13 years.
At CROI 2019, researchers described a second man, Adam Castillejo, dubbed the London patient, who also achieved long-term HIV remission after a stem cell transplant to treat Hodgkin lymphoma. In May 2016, he, too, received cells from a donor with a double CCR5-delta-32 mutation, but he underwent less aggressive pre-transplant conditioning chemotherapy, was able to stay on antiretroviral treatment and had milder graft-versus-host disease.
In September 2017, with no evidence of viable HIV, he stopped antiretroviral therapy. He has now been free of HIV for more than four years and his lymphoma is still in remission. Professor Yvonne Bryson of the University of California Los Angeles described the new case at the conference and an accompanying press briefing.
The middle-aged (post-menopausal) woman, a participant in an observational study called IMPAACT P1107, was diagnosed with HIV in 2013 and acute myeloid leukaemia in 2017 and she required a stem cell transplant. The study was designed to use previously screened umbilical cord blood with the double CCR5-delta-32 mutation, which is present in only around 1% of northern Europeans and is even rarer in other populations.
The woman remained on antiretroviral therapy for three years after the transplant. During that time, she had undetectable plasma viral load according to highly sensitive assays, undetectable HIV DNA in immune cells (reflecting the latent viral reservoir) and no evidence of replication-competent HIV.
As expected, her CD4 and CD8 T-cell counts fell after the conditioning therapy, but a year later they had rebounded and remained stable at around normal levels, while HIV-specific immune activation decreased. What’s more, she seroreverted, or became HIV antibody negative, a year after the transplant.
At that point, she decided to try a closely monitored antiretroviral treatment interruption. Fourteen months later – four and a half years after the stem cell transplant – she has not experienced viral rebound, has undetectable HIV-specific cellular immune responses, is still HIV antibody negative and her leukaemia remains in remission. Researchers have not been able to detect replication-competent latent HIV in nearly 75 million CD4 cells.
What factors are required for a stem cell cure?
Researchers are still attempting to learn why these three apparent HIV cures after stem cell transplantation were successful while other attempts have failed. Using stem cells from donors with a double CCR5-delta-32 mutation seems to be crucial.
At CROI 2014, researchers described two HIV-positive men in Boston who received stem cell transplants for cancer treatment from donors with normal, or “wild-type”, stem cells that lack the mutation. Despite high hopes, one man experienced viral rebound three months after stopping antiretrovirals and the other did so eight months after treatment interruption.
Hsu J et al (Bryson Y presenting). HIV-1 remission with CCR5∆32∆32 haplo-cord transplant in a U.S . women: IMPAACT P1107. Conference on Retroviruses and Opportunistic Infections, abstract 65LB, 2022.