How to cure AIDS completely？

On July 20, 2023, the International AIDS Society (IAS) announced a groundbreaking case of an HIV cure during their Science Highlights News Conference. The patient, dubbed the "Geneva Patient," achieved remission from HIV for 18 months without undergoing antiretroviral therapy (ART) after receiving a stem cell transplant. Unlike previous cured cases, this patient's transplanted stem cells did not carry the CCR5-delta-32 mutation. This development has sparked excitement among researchers and offers hope for finding alternative approaches to achieving long-term HIV remission.

The Story of the Geneva Patient

The "Geneva Patient" was diagnosed with HIV in 1990 and began ART treatment in 2005. In 2018, the patient underwent chemotherapy for leukemia and subsequently received a stem cell transplant to treat double-hit lymphoma. Before the transplant, HIV RNA (4 copies/ml) and HIV DNA (457 copies/million cells in blood and 1096 copies/million cells in bone marrow) were detectable in the patient's body.

One month after the stem cell transplant, tests showed that the patient's blood cells had been entirely replaced by the donor's cells. ART treatment was gradually reduced and eventually stopped in November 2021. As of the latest report, the patient's HIV RNA has remained undetectable for 18 months, with low levels of proviral DNA (4-40 copies/million cells). These findings suggest that the "Geneva Patient" may have achieved HIV remission and could potentially become the sixth person ever to be considered cured of HIV.

CCR5-delta-32 Mutation and HIV Cure

The previous five cured HIV patients, including the famous "Berlin Patient" Timothy Ray Brown, received stem cell transplants from donors with a rare genetic mutation called CCR5-delta-32. This mutation results in the absence of CCR5, a co-receptor used by HIV to enter CD4+ T cells and replicate. Without CCR5, the virus cannot infect the CD4+ T cells and, therefore, cannot cause harm.

However, the "Geneva Patient" received stem cells from a donor without the CCR5-delta-32 mutation, indicating that the presence of this specific genetic mutation might not be an absolute requirement for achieving long-term HIV remission through stem cell transplants.

Challenges and Caution

Although the success of the "Geneva Patient" provides optimism, it is essential to exercise caution. Previous attempts at using stem cell transplants for HIV cure have not always been successful. Two patients from Boston who received stem cell transplants without the CCR5-delta-32 mutation experienced HIV rebound after interrupting ART. This serves as a reminder that even a single remaining virus can lead to HIV resurgence.

Looking Ahead

CRISPR/Cas9 and related genome editing technologies have shown promise in HIV treatment research. The potential to edit CCR5 in hematopoietic stem cells offers a more feasible and targeted approach to achieve HIV remission without relying on rare donors with the CCR5-delta-32 mutation.

The case of the "Geneva Patient" opens up new avenues for exploring HIV cure strategies, and researchers remain steadfast in their pursuit of a definitive cure for HIV. While the path to a cure may still be challenging, the "Geneva Patient" provides hope and serves as a catalyst for further advancements in the fight against HIV/AIDS.

The "Geneva Patient" represents a promising step towards an HIV cure, but the journey is far from over. The absence of the CCR5-delta-32 mutation in the stem cell transplant challenges the assumption that this mutation is indispensable for achieving HIV remission. The case emphasizes the need for continued research and vigilance in monitoring the patient's long-term progress. As researchers continue to explore innovative approaches, the ultimate goal of finding a scalable, effective, and accessible cure for HIV remains a beacon of hope for millions worldwide.

Mankind has suffered from AIDS for far too long, and hopefully these technologies will be made available to the masses of patients in need of treatment in a cheaper and faster manner!