'Oslo patient' likely cured of HIV after getting stem cell transplant from his brother, who is genetically resistant to the virus

A 63-year-old man known as the Oslo patient is "likely cured" of HIV after a stem-cell transplant remodeled his entire immune system.

Prior to this case, a handful of other HIV patients who received similar transplants had entered long-term remission from the infection. In those cases, the donated cells came from people unrelated to the patients, but in the Oslo patient's case, the transplanted cells came from his brother. His sibling happened to carry a genetic mutation that made him resistant to HIV, doctors reported Monday (April 13) in the journal Nature Microbiology.

The mutation, called CCR5 delta 32, disables a protein on the surface of immune cells that HIV often exploits to trigger infection. The patient's brother carried two copies of this mutation, which effectively locks the virus out of cells that would normally be its prime targets.

"A sibling has a 25% probability of being a match for a transplant, and the frequency of CCR5Δ32/Δ32 is around 1%" in northern European populations, study co-author Dr. Anders Eivind Myhre, a hematologist at Oslo University Hospital, where the patient was treated, told Live Science in an email. "So it is an unlikely scenario, and we were not aware of the donor's CCR5 status before the transplant."

"Like winning the lottery twice"

The Oslo patient had been diagnosed with HIV in 2006, at age 44. In 2010, he started antiretroviral therapy (ART), which suppresses the virus's ability to replicate in the body and thus prevents the infection from progressing to AIDS. The treatment drove the HIV in the man's blood down to undetectable levels, which also stops the virus from being transmitted through sex. The patient has maintained this level of "viral suppression" from August 2010 to the present.

However, in 2017, the patient became fatigued, and his blood cell counts plummeted. The next year, he was diagnosed with a type of bone marrow cancer called myelodysplastic syndrome, in which new blood cells made in the bone marrow fail to mature. Initially, the patient responded well to a drug for the condition and entered remission, but he later relapsed, prompting his doctors to seek a bone marrow transplant instead.

Also known as hematopoietic stem cell transplants, bone marrow transplants involve infusing healthy, blood-making stem cells into the body to replace diseased ones. These new stem cells multiply and give rise to new red and white blood cells, ultimately remodeling the patient's blood supply and immune system.

At that point, the patient was referred to Myhre's care at Oslo University Hospital, and the team there searched for a bone marrow donor who happened to carry the coveted CCR5 delta 32 mutation. They were aware of similar cases where patients with HIV and blood cancer had received transplants with the mutation and then entered long-term remission from both their conditions. (More recently, there have been a few reported cases of remission without CCR5 delta 32, or with only one copy.)

Unfortunately, the team's search failed to turn up a compatible donor with double CCR5 delta 32, so the patient's 60-year-old brother donated his bone marrow instead, to at least treat the cancer. But on the day of the procedure, the medical team discovered that the sibling happened to have two copies of CCR5 delta 32.

The patient has said "he feels like he has won the lottery twice," study co-author Dr. Marius Trøseid, a group leader, professor and infectious-disease specialist at Oslo University Hospital, told Live Science. "He was cured for his bone marrow disease, which could be fatal, and he's also now cured for HIV, most likely."

Following the transplant, the patient did experience a complication known as graft-versus-host disease. This happens when the transplanted cells give rise to new immune cells that then see the patient's body as "foreign" and attack the tissues. But he was treated for this complication with an immune-modulating medicine, and over time, the new immune system successfully took over.

Two years out, the new cells had completely replaced the patient's original immune cells in the blood, bone marrow and gut, the study authors found in a thorough analysis.

"Most likely, it's a cure"

Trøseid was asked to evaluate the Oslo patient's case following the transplant, when a question emerged about whether he could safely stop ART. Tests confirmed that the patient's immune system had been completely transformed, leaving no trace of HIV in the blood. The team collected 65 million CD4 T cells — the primary targets of HIV infection — and found that none carried virus capable of replicating.

So, 24 months after his transplant, the patient was cleared to stop ART. Since then, there's been no sign of viral rebound — and Trøseid and colleagues have been on the lookout.

They thoroughly analyzed lymph tissues in the patient's gastrointestinal tract, which serve as the main hiding place for HIV in the body, and found no trace of the virus. They also ran tests with the patient's immune cells, and found that they responded well to common viruses, like the "mono" virus and influenza viruses, but did not react to HIV.

"So they function well, but they do not recognize HIV," Trøseid said. "It seems like his new immune system has never met HIV and does not recognize it."

Taken together, these analyses suggest the Oslo patient's case represents a "likely cure," Trøseid noted, though conservatively, scientists prefer to label such cases "sustained remission" from HIV. There's no consensus as to when a given patient can officially be declared cured, but from a practical standpoint, the Oslo patient no longer needs to take daily medications to keep the virus at bay.

"What will happen when some of these cure cases reach very old age and the immune system starts to decline a bit for other reasons? We don't know," he added. "I think we will just need to see. But most likely, it's a cure."

Trøseid thinks the myriad tests they ran in this study could be useful benchmarks for future transplants, to help doctors judge when a patient is in long-term remission. Studying these patients could also help reveal new and better strategies for controlling the virus, which are still needed.

"It's one of several stepping stones on the way to a functional cure," Trøseid said of studying these transplant cases. A functional cure would sustainably suppress HIV in the body without needing to completely eliminate it, as the latter would be a more difficult feat to achieve.

ART is very effective at stopping viral replication, disease progression and transmission, but it must be taken consistently for life. This presents logistical and monetary challenges for many people with HIV, some of whom also struggle to access ART due to the stigma that comes with acknowledging an HIV diagnosis. And while bone marrow transplants offer one route to long-term remission, the harsh procedures carry a lot of risks and are generally administered only to patients who need them for another serious condition, like cancer.

"The number of people living with HIV worldwide is more than 30 million, so it's also not feasible" to give them all transplants, Trøseid said. "We need to find other strategies to cure or control the virus."

Trøseid noted that recent trials suggest that engineered antibodies may be a promising solution for controlling the virus without ART. And in Europe, an international consortium called EU2Cure has formed to help spur the development of these and other potential HIV cures.

"Hopefully, we can move the threshold a little bit with each trial," he said, "and eventually, get a functional cure where a large fraction of people can live for a longer time without taking meds."