A man in Germany, known as the “Düsseldorf Patient,” represents a landmark case as one of the few individuals cured of the Human Immunodeficiency Virus (HIV). His journey began with an HIV diagnosis managed with daily medication. A subsequent and unrelated diagnosis of a life-threatening cancer necessitated a high-risk medical intervention. This treatment, aimed at saving his life from cancer, had the unintended consequence of also eliminating HIV from his body, providing a rare glimpse into biological mechanisms that could lead to a cure.
The Dual Diagnosis
In 2008, the patient was diagnosed with HIV, the virus that causes Acquired Immunodeficiency Syndrome (AIDS). HIV functions by targeting the body’s immune cells, specifically a type of white blood cell called the CD4 cell. The virus uses these cells to replicate itself and spread, progressively weakening the immune system. To manage this, he began antiretroviral therapy (ART), a combination of drugs that suppresses the virus’s ability to replicate but does not eradicate it from the body.
Four years after his HIV diagnosis, in 2012, the patient faced a second threat: Acute Myeloid Leukemia (AML). AML is an aggressive cancer of the blood and bone marrow characterized by the rapid production of abnormal white blood cells. These cancerous cells accumulate in the bone marrow, interfering with the production of normal blood cells and creating a life-threatening condition.
The patient’s doctors changed his ART regimen to avoid potential drug interactions with the chemotherapy needed to fight the leukemia. Despite initial courses of chemotherapy, the cancer returned in a relapse. This meant that standard chemotherapy was failing, forcing his medical team to consider a much more radical and dangerous therapeutic option, which set the stage for his HIV cure.
The Stem Cell Transplant Procedure
With the leukemia proving resistant to chemotherapy, the medical team turned to an allogeneic stem cell transplant. This is a complex and high-risk intervention reserved for treating aggressive blood cancers that do not respond to other treatments. It is not considered a treatment for HIV due to its inherent dangers, but the goal was to replace the patient’s cancerous bone marrow with a healthy system from a donor.
The process began with a conditioning regimen, which involved administering high-dose chemotherapy to destroy the patient’s existing bone marrow and cancerous cells. This action eliminated his entire immune system, leaving him highly vulnerable. The destruction of his native marrow was a necessary step to make space for the new donor cells and to prevent his body from rejecting them.
Following the conditioning regimen, the patient was infused with healthy, blood-forming stem cells from a compatible donor. These infused cells travel to the bone marrow, where they begin a process called engraftment. Over several weeks, the donor stem cells establish themselves and start to produce new, healthy blood cells, with the aim of this new system functioning as his own.
The CCR5 Gene Mutation
The success of the procedure in curing HIV hinged on a specific genetic characteristic of the stem cell donor. The medical team sought a donor who was not only a tissue match but also possessed a mutation in the gene for a protein called C-C chemokine receptor 5, or CCR5. This protein is on the surface of immune cells and functions as a primary co-receptor, or doorway, that most common strains of HIV use to infect cells.
The specific genetic trait is known as the CCR5-delta 32 (CCR5Δ32) mutation. It is a deletion in the CCR5 gene that results in a nonfunctional protein that does not get placed on the cell surface. Without this CCR5 doorway, the most prevalent variants of HIV are physically blocked from entering and infecting immune cells.
Individuals who inherit this mutation from one parent produce fewer CCR5 receptors. Those who inherit it from both parents—a state known as being homozygous for the mutation—lack the CCR5 receptor entirely, granting them a natural high resistance to HIV infection.
The search for a donor was challenging, as the individual needed to be a close immunological match while also having this rare genetic profile, found in about 1% of the population of Northern European descent. A suitable donor was identified, and her stem cells were used for the transplant. As these mutated cells engrafted, they built a new immune system that was naturally resistant to the virus he already had.
This strategic selection was the element that transformed a cancer treatment into an HIV cure. The transplanted cells not only cured his leukemia by replacing the cancerous marrow but also established an HIV-resistant immune system. This new system prevented any residual virus from replicating and re-establishing an infection.
Confirmation of the Cure and Broader Implications
After the transplant, the patient remained on ART for several years while his new immune system established itself. In November 2018, nearly six years after the transplant, his medical team stopped all antiretroviral medication in a process known as an analytic treatment interruption. If any replication-competent virus remained in his body, it would be expected to rebound and become detectable in the blood.
For more than four years after stopping ART, the patient underwent intensive monitoring. Researchers used ultrasensitive tests on samples of his blood and tissues to search for any trace of HIV or an immune response to the virus. No viral rebound occurred, and with no active virus detected, the international research consortium declared him cured in February 2023.
This case provides proof that a cure for HIV is biologically achievable. However, the stem cell transplant procedure is too dangerous to be a standard treatment for HIV, which is manageable with ART. The transplant carries risks, including infections during immune suppression and graft-versus-host disease, where the donor’s immune cells attack the recipient’s body.
The difficulty of finding a donor who is both a tissue match and has the rare CCR5 mutation further limits its use. The significance of this case lies not in the treatment itself but in the biological lesson it provides. It demonstrates that replacing an immune system with one genetically resistant to HIV can eradicate the virus.
This principle is now guiding research toward safer strategies, such as gene therapy techniques aimed at editing a patient’s own immune cells to disable the CCR5 gene. This approach could replicate the curative effect without a high-risk transplant.