From the Berlin patient case to the Oslo patient: ten people have now been cured of HIV

What in 2009 seemed like an unrepeatable milestone—the case of Timothy Ray Brown, known as the Berlin Patient and the first documented case of HIV cure—is no longer an exception. Ten people worldwide have managed to eliminate the virus after undergoing a stem cell transplant to treat a hematological cancer. The latest published case, the Oslo patient, appears today in the journal Nature Microbiology. The study is led by Oslo University Hospital and includes participation from IrsiCaixa—an institute jointly promoted by the ”la Caixa” Foundation and the Department of Health of the Government of Catalonia—at the national level.

“These milestones allow us to better understand how cure occurs and to move toward strategies that can be applied to all people living with HIV. The fact that there are now ten patients in remission is no coincidence—it is the result of more than a decade of international research,” says Javier Martínez-Picado, an ICREA researcher at IrsiCaixa and coordinator of IciStem 2.0, the international consortium dedicated to studying HIV cure through stem cell transplantation and the one that has documented the most cure cases worldwide.

The Oslo case

The Oslo patient is a 62-year-old man living with HIV who was diagnosed with a cancer of the immune system that required a stem cell transplant. In such cases, donors with the CCR5Δ32 genetic mutation are sought, as it prevents the virus from entering cells.

“Repopulating the immune system with cells carrying this mutation prevents HIV from infecting the new cells. In the Oslo case, we did not find a compatible donor in registries and opted for his brother, who unexpectedly carried the mutation. This patient has therefore become the first cured case using a transplant from a sibling and, together with the City of Hope patient (California), one of the oldest among the documented cases,” explains Maria Salgado, researcher at IrsiCaixa and IGTP.

Two years after the transplant, and under medical supervision, antiretroviral treatment was discontinued. Three months later, no intact viral DNA or replication-competent virus was detected. HIV was also not found in the gut, one of the main viral reservoirs. 

In addition, the immune response specific to the virus progressively declined, suggesting that the immune system stopped detecting it because it was no longer present. Four years after stopping medication, the patient still shows no detectable trace of the virus.

What do these 10 cases teach us?

To date, IciStem has followed 40 people with HIV who underwent stem cell transplantation, four of whom have stopped treatment and maintain undetectable virus levels. “These four cases, together with six others described outside the consortium, make up the ten HIV remission cases known today. 

We expect more, as we have a large cohort under follow-up and some cases currently being evaluated to determine whether treatment interruption is feasible and whether they can control the virus without medication. Treatment is only stopped when viral markers are extremely low and the clinical situation is stable,” explains Salgado.

The combined analysis confirms the protective role of the CCR5Δ32 mutation: when the donor had two copies of the mutation, HIV remission was achieved. In contrast, in several cases with one or no copies, the virus reappeared after stopping medication. 

However, there are exceptions: patients known as Berlin 2 and Geneva achieved cure despite their donors not having the double mutation. This indicates that, although the double CCR5Δ32 mutation increases the chances of success, it is not the only mechanism involved.

“We know that transplantation alone significantly reduces the HIV reservoir—something no other medical intervention has achieved so far. However, it is a high-risk procedure and not applicable to the general population living with HIV, who already have safe and effective antiretroviral treatments,” adds Martínez-Picado.

Beyond transplantation

The current challenge is to translate these findings into less invasive strategies. One of the approaches being explored by IrsiCaixa’s GREC group is CAR-T cell therapy, a technology already well established in cancer treatment. It involves modifying a patient’s own immune cells so they can recognize and destroy HIV target cells. 

“The idea is to eliminate CD4+ T cells infected with HIV, but also those susceptible to infection—all without affecting the ‘factory’ of CD4+ T cells: the stem cells in the bone marrow, which cannot be infected and are responsible for regenerating the immune system. It would be like ‘cleaning’ the circulation of infected cells so the body can repopulate itself with healthy ones,” explains Salgado, who leads a project evaluating this strategy. “We are still at a very early stage and are currently studying whether it is feasible,” she adds.

Other teams are also investigating gene therapies to modify the CCR5 gene and induce the well-known CCR5Δ32 mutation, thereby blocking viral entry into cells, although these approaches are also in early stages.

Although transplantation is not a broadly applicable solution, these ten cases demonstrate something that seemed impossible just fifteen years ago: HIV can be cured.