The Geneva patient: Another score on the HIV remission board

Another HIV patient may be on the way to a cure following stem cell therapy using wild-type (WT) CCR5 donor cells for a rare and aggressive blood cancer.

The ‘Geneva patient’ had no viral rebound 20 months after interruption of his antiretroviral therapy (ART) and undergoing allogeneic hematopoietic stem cell transplantation (aHSCT) using cells from a CCR5-WT/WT donor, said Dr Asier Sáez-Cirión from the Institut Pasteur, Paris, France, at IAS 2023.

The patient is a Caucasian male diagnosed with HIV in 1990. He has received the very first generation of antiretrovirals and has been virally suppressed since 2005. In 2018, he developed biphenotypic sarcoma for which he needed aggressive treatment including aHSCT. [IAS 2023, abstract 5819]

Chimerism was achieved very quickly (<1 month) and the viraemia has remained undetectable after aHSCT, said Sáez-Cirión. ART was simplified progressively and then stopped in 2021. “The viraemia has remained undetectable for 18 months so far.”

Reasons for absence of viral rebound

The patient has been on immunosuppressive therapy for graft-versus-host disease (GVHD) for a long time. The disease relapsed upon treatment cessation. He has been treated since with the JAK/STAT inhibitor ruxolitinib.

“We do not know whether the GVHD episodes contribute to the emptying of the viral reservoir. There has been a report showing how allogeneic immunity may be enough in some cases to clear the viral reservoir and achieve something similar to a cure,” Sáez-Cirión explained.

Natural killer cells may also play a role in controlling the infection. Ruxolitinib may have also triggered the suppression of viral reactivation, but this remains to be verified, he added.

Is stem cell therapy the way out of HIV?

Durable HIV remission after ART discontinuation has been reported following aHSCT from CCR5-Δ32/Δ32 homozygous donors. “It is thought that the presence of the CCR5-Δ32/Δ32 mutation may be necessary to achieve HIV cure after aHSCT,” said Sáez-Cirión. “For the Geneva patient, CCR5-WT/WT was chosen in the absence of a compatible CCR5-Δ32/Δ32 donor.”

The ICISTEM study group were able to detect the virus, replication-competent DNA, and low-level viral replication prior to aHSCT, but all markers dropped quickly following aHSCT. “We have not found HIV DNA in the multiple biopsies from the gut. There was no transcriptional activity, and we could not amplify any virus from cell cultures. All virological markers measured 15–20 months after treatment interruption have remained undetected,” Sáez-Cirión shared.

Caveats

The Geneva patient follows five other patients who have been ‘possibly cured’ of HIV, adding to the growing pool of patients who have achieved remission following bone marrow transplant for blood cancer.

However, two patients (ie, Boston patients) who have received aHSCT with the WT mutation have rebounded after stopping ART. Sáez-Cirión remains hopeful though, stating that undetectability of the virus is highly likely if there is still no sign of it after a year.

Professor Sharon Lewin from the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia, and International AIDS Society President, said that while the case is ‘promising’, the patient must be watched closely over the next months and years. “We learned from the Boston patients that even a single particle of the virus can lead to HIV rebounding.”

Nonetheless, the current data highlights the possibility of long-term viral remission after aHSCT with the CCR5-WT/WT mutation. The growing remission cases may also open new paths in research to finally find a cure for HIV.