Editor's Note: The "Berlin Patient" is renowned as the first person in the world to be cured of HIV, marking a significant milestone in medical history. Over a decade later, the pioneering team at Germany’s Charité – Universitätsmedizin Berlin has announced the successful treatment of the "Next Berlin Patient," representing the 7th global case of HIV cure. Publicly available data indicates that this patient has remained virus-free for over five years without antiretroviral therapy (ART). What sets this case apart is that the treatment method differed from those used in previous cures. Detailed treatment information will be presented at the 25th International AIDS Conference (AIDS 2024) in Munich on July 24.Significant Progress in HIV Treatment
The field of HIV treatment has seen remarkable progress, with standardized antiretroviral therapy (ART) significantly extending the lifespan and improving the quality of life for HIV-positive individuals. Despite these advancements, HIV is still considered an incurable disease. However, in rare cases, stem cell transplantation can completely eradicate the virus from the patient’s body.
Stem cell transplantation is mainly used for HIV-positive patients who also have certain types of leukemia or lymphoma and require a donor with the CCR5 mutation. This therapy involves transplanting healthy donor stem cells into the patient to rebuild their immune system, effectively fighting cancer and potentially eliminating HIV. Previously, scientists believed that finding a stem cell donor with specific genetic characteristics was crucial for the success of this treatment.
The Role of CCR5
HIV-1 enters host cells by binding to the CD4 receptor, requiring a co-receptor for membrane fusion, with CCR5 being the primary co-receptor. Certain CCR5 mutations can significantly increase or decrease the likelihood of HIV infection and the progression of the disease.
The CCR5Δ32 mutation involves a 32-base pair deletion after the 185th amino acid codon in the CCR5 allele coding region, preventing CCR5 from being properly expressed on the cell membrane. As a result, HIV-1 gp120 cannot effectively bind to CCR5Δ32, preventing the virus from entering host cells. The CCR5Δ32 mutation can be homozygous or heterozygous; individuals with the homozygous mutation are resistant to HIV-1 infection, while those with one mutated allele progress to AIDS more slowly. Approximately 1% of Europeans carry the CCR5Δ32 mutation. Finding a stem cell donor who matches the recipient and carries the homozygous mutation can potentially cure both cancer and HIV through stem cell transplantation.
The Berlin Patient and Subsequent Cases
In 2008, researchers at Charité – Universitätsmedizin Berlin were the first to demonstrate the effectiveness of stem cell transplantation in treating HIV, known as the breakthrough case of the “Berlin Patient.” Since then, four more people worldwide have successfully cleared HIV using similar methods. Now, Charité has achieved another breakthrough, curing an HIV-positive patient with acute myeloid leukemia (AML) using a slightly modified approach.
Treatment of the “Next Berlin Patient”
This anonymous 60-year-old German male was diagnosed with HIV in 2009 and AML in 2015. To treat AML, the patient underwent a stem cell transplant in October 2015. Notably, unlike previous cases, the research team could not find a donor with the homozygous mutation but found a donor with a heterozygous mutation, meaning the donor was not completely immune to HIV.
Surprisingly, despite using this unconventional strategy, the patient stopped ART in September 2018 after the stem cell transplant. Over five years of close monitoring and follow-up, no HIV rebound has been observed, opening new research directions and possibilities for HIV treatment.
Summary of HIV Cure Cases
The seven known cases of HIV cure include:
- The Berlin Patient (2007): Male, AML, CCR5Δ32/Δ32
- The London Patient (2016): Male, Hodgkin Lymphoma, CCR5Δ32/Δ3
- The Düsseldorf Patient (2011): Male, AML, CCR5Δ32/Δ32
- The New York Patient (2017): Female, AML, CCR5Δ32/Δ32
- The City of Hope Patient (2019): Male, AML, CCR5Δ32/Δ32
- The Geneva Patient (2018): Male, AML/Leukemia/Sarcoma, CCR5WT/WT
- The Next Berlin Patient (2015): Male, AML, CCR5Δ32/WT
Understanding the Success of Heterozygous Stem Cell Transplant
Currently, the specific mechanism by which the heterozygous stem cell transplant achieved HIV cure in this patient is not clear. Professor Christian Gaebler pointed out that the rapid replacement of the old immune system with the new one might be a key factor. In this case, the process was completed in less than 30 days. Additionally, the donor’s immune system may have had unique properties, such as highly active natural killer cells, capable of detecting and eliminating minor HIV activity. Researchers are exploring these potential factors to provide new insights for future HIV treatments.
