Ten years ago, an HIV patient known as the “Berlin patient” was deemed cured. Until this past week, his HIV-rebound-free status was unique. But he has now been joined by a second patient, the “London patient,” according to an international team of scientists. They presented their findings in Seattle, at the Conference on Retroviruses and Opportunistic Infections (CROI). Before the CROI event concludes, members of the team are expected to present additional findings about a third HIV-rebound-free patient, the “Düsseldorf patient.”
In both the London and Düsseldorf patients, scientists found no rebound of HIV following stem cell transplants that were administered as part of cancer treatment. Both patients had ceased taking their HIV medication.
The transplanted donor cells had a gene defect that prevents expression of CCR5, an HIV receptor. CCR5 is one of the critical entry gatekeepers that HIV can exploit to infect cells.
Details about the London patient appeared March 6 in the journal Nature, in an article titled, “HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation.” The article emphasizes differences between the treatments received by the Berlin and London patients. Notable differences were that the Berlin patient was given two transplants, and underwent total body irradiation, while the London patient received just one transplant and less intensive chemotherapy.
The London patient “experienced mild gut graft versus host disease,” the article’s authors wrote. “Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained through a further 18 months.
“Although at 18 months post-treatment interruption it is premature to conclude that this patient has been cured, these data suggest that single allo-HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings further support the development of HIV remission strategies based on preventing CCR5 expression.”
The Düsseldorf patient stopped his HIV medication for a shorter period of just three-and-a-half months, but has also remained HIV free. Using the most sensitive techniques available to date, only traces of HIV DNA were detected.
The London and Düsseldorf patients show that after a single transplant and with even mild cancer chemotherapy and without radiation, remission may be achieved.
Both the London patient and the Düsseldorf patient were registered with the IciStem program. IciStem is the International Collaboration to guide and investigate the potential for HIV cure by Stem Cell Transplantation.
Both the London and Düsseldorf patients experienced mild graft-versus-host disease, which may also have played a role in the loss of HIV-infected cells.
“By achieving remission in a second patient using a similar approach, we have shown that the Berlin patient was not an anomaly, and that it really was the treatment approaches that eliminated HIV in these two people,” said the study’s lead author, Ravindra Gupta, MD, PhD, a professor at University College London, division of infection & immunity.
The researchers caution that the approach is not appropriate as a standard HIV treatment due to the toxicity of chemotherapy, but it offers hope for new treatment strategies that might eliminate HIV altogether.
“Continuing our research, we need to understand if we could knock out this receptor in people with HIV, which may be possible with gene therapy,” noted Gupta.