- A man in Norway has achieved long-term HIV remission after a stem cell transplant, adding to a small but growing group of similar cases.
- Researchers say rare genetic factors, immune responses, and medication appear to work together to eliminate hidden HIV reservoirs.
- While not a practical cure for most people, these cases are helping scientists better understand the complexities of how to achieve HIV remission.
An adult man in Norway has been functionally cured of HIV following a stem cell transplant. He joins a small number of patients worldwide who have achieved similar outcomes.
Advancements in prevention and treatment, including PrEP and antiretroviral therapy (ART), have drastically improved outcomes and reduced the risk of HIV transmission.
In these cases, “functional cure” refers to long-term HIV remission without the need for ongoing treatment.
Only a small number of patients have achieved remission in this manner, but a new report adds to that growing body of evidence.
The “Oslo patient,” as he is known in the report, is a 63-year-old man who is documented as being functionally cured five years after undergoing HSCT to treat myelodysplastic syndrome.
Researchers affirmed his remission status by testing blood, gut, and bone marrow samples, all of which revealed no detectable viral reservoirs.
The case, which is documented in the journal
Most, though not all, documented cases of HIV remission following a stem cell transplant have involved patients receiving stem cells from donors with the CCR5Δ32 mutation.
The CCR5Δ32 mutation confers resistance to the most common forms of HIV-1, the predominant HIV variant.
HIV uses CCR5 receptors on immune cells as an entry point to infect them. However, the CCR5Δ32 mutation prevents cells from expressing these receptors, effectively blocking the virus from entering and establishing infection.
The Oslo patient is no exception, having received a stem cell transplant from a sibling carrying the mutation. The presence of the mutation appears to play a key role in long-term remission, but it is not the only factor.
Steven Deeks, MD, a professor of medicine at UCSF in the Division of HIV, Infectious Diseases, and Global Medicine at Zuckerberg San Francisco General Hospital, framed the development as a step forward in an evolving understanding of HIV remission. Deeks wasn’t involved in the study.
“There have now been 10 successful transplants. Each is unique, but they collectively show that there are multiple ways a bone marrow transplant can help cure HIV. We learn from each case,” he said.
Augusto Dulanto, MD, an assistant professor of Medicine in the Department of Medicine’s Division of Infectious Diseases at Vanderbilt University, who wasn’t involved in the research, called the case “a cause for optimism” in HIV research.
The Oslo patient is among just a few others from around the world, including London, Berlin, and New York, who have been functionally cured of HIV following a stem cell transplant in which the donor had the CCR5Δ32 mutation.
In all of those cases, patients received stem cell transplants to treat conditions other than HIV, and remission occurred as a consequence of that treatment.
HIV is adept at hiding in various cells throughout the body in a latent state, including in the gut, making it extremely difficult to eliminate and prone to rebound if treatment is stopped. However, HSCT appears to be one method through which HIV can be almost entirely eliminated.
HSCT involves destroying much of a patient’s existing bone marrow and immune system with chemotherapy or radiation, then infusing healthy donor stem cells to rebuild the immune system. This process can drastically reduce the number of cells harboring HIV, which is known as the viral reservoir.
Humans have two copies of the CCR5 gene; when both carry the CCR5Δ32 mutation, cells are highly resistant to HIV, whereas a single copy confers only partial resistance. When donor cells with this mutation are used in a transplant, they can confer that resistance to the recipient, increasing the likelihood of remission.
“In this case, the sibling had the mutation in both the mother’s and the father’s side, which means he was homozygous for that mutation. And that is the key characteristic that allows for most cases similar to this to be successful,” Dulanto said.
However, some patients have been functionally cured of HIV following a stem cell transplant, even when the donor does not carry the mutation, as in the case of a
In these cases, researchers increasingly look to a well-known complication of the procedure — graft-versus-host disease (GVHD) — as part of the explanation for remission. As the donor immune system takes hold, it can aggressively attack the patient’s remaining cells.
Under other circumstances, this is harmful. However, in patients with HIV, that immune response may also target and destroy cells harboring the latent virus, a phenomenon referred to as a “graft-versus-reservoir” effect.
The graft-versus-reservoir effect is theorized to be another piece of the puzzle in achieving HIV remission.
Yet there are other moving parts, said Marshall Glesby, MD, PhD, associate chief of the Division of Infectious Diseases and director of the Cornell HIV Clinical Trials Unit at the Weill Cornell Medical College, told Healthline. Glesby wasn’t involved in the research.
“The graft-versus-reservoir effect and CCR5Δ32 mutation are kind of at the heart of things, but these patients are often receiving either prophylactic or therapeutic measures to counteract graft-versus-host disease, some of which are drugs that may have effects on the HIV reservoir,” he said.
Researchers note that ruxolitinib and vedolizumab, two drugs commonly used to treat GVHD, also appear to have anti-HIV properties that may contribute to the complete elimination of the virus. Simultaneously, antiretroviral therapy is also part of recovery, preventing any surviving virus from infecting the newly forming immune cells.
Taken together, this combination of treatments and immune-related factors may create the conditions in which HIV viral reservoirs are reduced or eliminated to the point where the virus can no longer rebound, potentially resulting in sustained remission, even in the absence of the protective CCR5Δ32 mutation.
Antiretroviral therapy (ART) has advanced to such a point that individuals with HIV are able to suppress the virus to undetectable levels, meaning there is “effectively no risk” of transmitting HIV.
The case of the Oslo patient is further proof that curing HIV is possible, though unlikely for most people. The authors write that using HSCT to cure HIV is “not a scalable strategy” owing to the serious and high risk nature of the procedure.
HSCT carries a significant risk of death, with a mortality rate of 10–20% within the first year after treatment.
Even if the procedure is successful, remission from cancer is not guaranteed. Cancer relapse is the leading cause of death following HSCT among those with HIV and the general population.
While ART requires lifelong use, it offers effective and generally well-tolerated viral suppression and is far more accessible than HSCT.
“The HIV treatments that we have nowadays are often just one pill per day, which is similar to how we treat hypertension. A procedure like HSCT has to be worthwhile, such as in cases where you may be able to simultaneously cure both HIV and a hematologic malignancy,” Dulanto said.
Still, Glesby points out that, despite its effectiveness, ART is still not a cure, and there are plenty of individuals with HIV who may still have difficulty taking daily medication. Furthermore, having HIV is still linked with a number of other conditions.
“Even when HIV is controlled, there’s still ongoing activation of the immune system and inflammation in many people that contributes to a number of comorbidities, including heart disease and age-related conditions,” he said.
That is to say, there is still a real drive among researchers to find a true cure. Despite the limitations of HSCT as a practical HIV treatment, the Oslo patient case advances our understanding of what it takes to achieve remission, helping to clarify the roles of genetics, immune response, and drug therapy on the path toward that goal.
“There’s still interest in achieving long-term control of HIV without having to take medications. There’s also research to try to improve tolerability and reduce the frequency of medication administration. All of these things are being done in parallel with the ultimate goal of helping people with HIV live longer and more productive lives,” Glesby said.
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