A man in Germany has been cleared of human immunodeficiency virus (HIV), according to researchers, after receiving a stem cell transplant from an HIV-resistant donor. The 53-year-old man, known as the “Düsseldorf patient,” received a stem cell transplant within his bone marrow in 2018, and has remained HIV-free since. Administered in conjunction with an already well-known treatment, antiretroviral therapy (ART), the transplant seems to have eliminated all traces of HIV stored throughout the man’s body.
Antiretroviral Therapy
In recent years, patients with HIV have experienced a reduction in the presence of the virus within the body with ART. Antiretroviral drugs prevent the virus from replicating in the body, allowing the immune system to repair itself and lowering the viral load. However, while treatment with ART can bring virus levels down to almost undetectable levels, traces, or “reservoirs,” of the virus remain in some cells throughout the body. In order for the reservoirs to be fully removed, and thus for a patient to be fully cleared of the virus, researchers are looking to novel stem cell treatments as a potential solution.
Novel Stem Cell Treatment
In 2007, Timothy Ray Brown, previously referred to as the “Berlin patient,” was the first to receive the novel treatment, and the first person to be declared free of the virus. The treatment consisted of destroying cancerous bone marrow cells, which Brown had developed as a result of acute myeloid leukemia, and replacing them with stem cells from a healthy donor. Donated stem cells contain a genetic mutation that prevents the expression of a protein called CCR5. CCR5 is the protein through which HIV enters immune cells, and when unexpressed, stops the virus from spreading further. The second patient, Adam Castillejo, or the “London patient,” was declared free of HIV in 2019 after receiving the stem cell transplant.
In 2013, the Düsseldorf patient received the stem cell treatment after being diagnosed with acute myeloid leukemia. With the patient’s viral load at already undetectable levels as a result of receiving
ART, researchers led by virologist Björn-Erik Jensen at Düsseldorf University Hospital in Germany then tested tissue and blood samples to confirm the treatment’s efficacy. Jensen and the team continued to find evidence of HIV’s presence in the immune system, as well as HIV DNA and RNA in the patient’s body. Despite this, the virus continued to fail to replicate even when the patient’s cells were transplanted into mice. Finally, the patient’s cessation of ART confirmed that the HIV present could no longer replicate.
Commenting in Nature, Ravindra Gupta, a microbiologist at the University of Cambridge, UK, believes the study confirms that targeting CCR5 is the most likely contender for a future cure.
Implications for Future Treatment Methods
Despite the favorable results, it is unlikely that patients without leukemia will be able to receive the treatment in the near future, due to risks associated with the transplantation of bone marrow. Jensen reports that he and his team have treated other patients with stem cell transplants, though it remains too early to tell if they are also virus-free.
Other researchers are focused on research to isolate a patient’s stem cells and modify them to block or disable the CCR5 receptor. The hope is that this might eliminate the need for donor stem cells and the riskier bone marrow transplantation procedure.
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