Breakthrough leads to the second successful eradication of HIV from a patient
Researchers in London may have cured a man of HIV in the second documented case of prolonged HIV remission. The patient - called “the London patient” for confidentiality - was diagnosed with HIV in 2003, and began retroviral therapy in 2012; shortly thereafter, he was diagnosed with Hodgkin’s lymphoma. Hodgkin’s lymphoma is often resistant to chemotherapy, necessitating a complete bone marrow transplant. The transplant procedure involves radiation therapy to destroy the patient’s cancerous immune cells, followed by the regeneration of the immune system from the bone marrow tissue of a compatible donor. The treatment is toxic, and often fails to result in complete remission; however, for many, it is the last line of defence against a ruthless disease. Once the transplant was complete and the London patient had recovered, they appeared to be HIV free.
HIV infects the immune cells of the host, entering through receptors present on the cell surface. In the early 2000’s, researchers discovered that some individuals were resistant to the disease due to the presence of a mutation in the cell surface receptor CCR5. After further investigation, it was revealed that some strains of the viral subtype HIV-1 exploit the CCR5 receptor for cell entry; the mutation resulted in the production of defective receptors, preventing the virus from entering the immune cells. Researchers hypothesized that this receptor may someday be useful for the treatment of HIV.
Fast-forward a decade, and their idea for a treatment has finally come to fruition - albeit not in the way they imagined. In an article published in 2009, a team of researchers reported that they had driven HIV into remission via a bone marrow transplant. The research team were treating a patient with both leukaemia and HIV when they proposed treating both diseases with a bone marrow transplant from a donor with the CCR5 mutation. The recipient, dubbed “the Berlin patient,” underwent complete bone marrow irradiation followed by the mutated bone marrow transplant. It appears as though the CCR5 mutant immune cells completely replaced the patient’s original cells, thereby conferring resistance to the disease. The patient has remained in both cancerous and HIV remission since treatment.
The treatment has been attempted multiple times since the original publication without success. Researchers in London recently published results indicating they had successfully eradicated both diseases in a second patient using a similar method to that which was performed on the Berlin patient. The London patient arrested antiretroviral therapy 16 months post-op and has been in confirmed HIV remission for the past 18 months.
The results of both studies have demonstrated that the elimination of HIV – once thought to be incurable – is indeed possible. The risks of treatment for otherwise healthy individuals, however, almost certainly outweighs the benefits. As mentioned, the irradiation of an HIV patient’s bone marrow is toxic. Successful destruction of all host immune cells is usually tough to achieve, and the risk of secondary infection post-irradiation is high. Additionally, finding a matching bone marrow donor is a difficult endeavour under the best of circumstances; locating a matching donor with a CCR5 mutation is exponentially more troublesome. Unfortunately, the combination of risk and donor match rarity likely relegates this treatment to the realm of experimental medicine, and nothing more. For those patients who are concurrently infected with HIV and a cancer necessitating bone marrow transplantation, this treatment may be an option; however, the availability of donors with a mutated CCR5 gene may inhibit widespread application across HIV and cancer patients. For other HIV patients, until a viable cure is discovered that involves less risk than bone marrow transplantation, antiretroviral therapy will likely remain the prescribed course of treatment. Antiretrovirals are effective, inducing nominal side effects in the majority of patients while reducing HIV in the blood to undetectable levels.
Although the London and Berlin patients are not the blinding beacon of hope that some media outlets have described, they are important actors in the conversation surrounding HIV, and medicine in a broader sense.
A cure is generally touted as the goal of most disease research. When the cure risks causing symptoms far more severe than the pharmaceutically treated disease, however, our conversation requires a recalibration. Cures are a reductionist’s dream, eliminating the need for treatment beyond initial delivery. When the cure exists on the precipice between the experimental and the extreme, however, careful consideration must be used in determining the appropriate trade-off between risk and reward.