16 March 2020

A second patient appears to have been cured of HIV after successfully undergoing stem cell transplantation from a donor with an HIV-resistant gene, it has been announced.

Known only as “the London patient”, the patient has no active viral infection in the blood 30 months after stopping anti-retroviral therapy.

Remnants of integrated HIV-1 DNA remained in tissue samples. These were also found in the first patient to be cured of HIV, in Berlin in 2011, the researchers report. However, writing in The Lancet HIV, the authors suggest these can be regarded as “fossils” because they are unlikely to be capable of reproducing the virus.

Professor Ravindra Kumar Gupta, University of Cambridge, who led the study, cautioned that this stem cell transplantation approach was not a treatment that could be used in all HIV-positive people.

“It is important to note that this curative treatment is high-risk, and only used as a last resort for patients with HIV who also have life-threatening haematological malignancies,” he said. “Therefore, this is not a treatment that would be offered widely to patients with HIV who are on successful antiretroviral treatment.”

The patient underwent one stem cell transplantation from a donor who did not express the CCR5 gene. The patient received a reduced-intensity chemotherapy drug regimen without whole body irradiation, and was found to be in remission in 2019.

Ultrasensitive viral load sampling of the patient’s cerebrospinal fluid, intestinal tissue, or lymphoid tissue was performed at 29 months after interruption of antiretroviral therapy (ART) and viral load sampling of their blood at 30 months.

At 29 months, CD4 cell count was measured, and the extent to which the patient’s immune cells have been replaced by those derived from the transplant.

The research team found that there was no active viral infection detected in samples of the patient's blood at 30 months, or in their cerebrospinal fluid, semen, intestinal tissue, and lymphoid tissue 29 months after stopping ART.

The patient had a healthy CD4 cell count and 99% of the patient's immune cells were derived from the donor’s stem cells.

The research team then used a mathematical modelling to predict the probability of cure. They determined that if 80% of patient’s cells are derived from the transplant, the probability of cure is predicted at 98%; and if they have 90% donor derived cells, they predict a 99% probability of cure.

They say this case study represents a step towards a less intensive treatment approach, showing that the long-term remission of HIV can be achieved with one stem cell transplant using reduced intensity drug regimens and without total body irradiation.

Study co-author Dr Dimitra Peppa from the University of Oxford said: “Gene editing using the CCR5 has received a lot of attention recently. The London and Berlin patients are examples of using the CCR5 gene in curative therapies outside of gene editing. There are still many ethical and technical barriers - e.g. gene editing, efficiency and robust safety data - to overcome before any approach using CCR5 gene editing can be considered as a scalable cure strategy for HIV."


Source: Gupta RK, Peppa D, Hill AL, Gálvez C, Salgado M, Pace M, McCoy LE, Griffith SA, Thornhill J, Alrubayyi A, Huyveneers LEP, Nastouli E, Grant P, Edwards SG, Innes AJ, Frater J, Nijhuis M, Wensing AMJ, Martinez-Picado J, Olavarria E (2020) “Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report”, Lancet HIV, doi: 10.1016/S2352-3018(20)30069-2

 

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