Pepe Alcamí
IDIBAPS researcher and scientific director of the HIV Unit at Hospital Clínic de Barcelona
The article reports a case of cure of HIV infection in a patient receiving a bone marrow transplant for relapsed leukaemia with no other therapeutic option. Like the so-called London and Berlin patients, the transplant was performed with cells from a donor who carries a genetic deletion in one of the major HIV receptors, making the cells resistant to infection.
What is new about this description compared to previous ones? The application of more advanced reservoir detection technologies and a more in-depth immunological study of the response to HIV. The virus is what is detected and the immune response is a mirror of whether HIV is still present. The patient has no reoccurrence of viraemia four years after stopping treatment, so the chances of being cured are very high.
Two aspects are striking and interesting: one is the detection of HIV genetic fragments that are apparently defective because the virus cannot be isolated. This is clearly seen and has not been reported in previous cases. On the other hand, a cellular response to HIV is detected in the transplanted cells. This indicates that after transplantation and despite the fact that the patient was on antiretroviral treatment, HIV persisted to the level of an immune response that has been decreasing over time. This is very interesting because it suggests that the key element for cure is that the donor cells are resistant to infection because of the defect in the CCR5 gene. Although HIV persists for some time and replicates despite antiretroviral treatment, the fact that it cannot infect new cells leads to its extinction.
What are the implications for everyday practice? None. The work has great merit, it is well done and by prestigious groups, but, like all the cases of eradication or functional cure that we publish, they are exceptional cases that cannot be extended to practically all patients. It is unethical to perform a bone marrow transplant if it is not indicated for a haematological disease because the mortality of the procedure is very high (>40%). Achieving this effect with gene therapy - nullifying the CCR5 gene in progenitor cells or CD4 lymphocytes - as always discussed and suggested by the authors in the last paragraph, is still a distant goal. The trials conducted so far have yielded very transient and clinically irrelevant results. This is important to note.
In summary, the work represents an advance in our knowledge, but the strategy is unfeasible for patients living with HIV, it does not represent hope for the vast majority.