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‘Geneva’ HIV patient possibly cured in new case

Another HIV patient has been off antiretroviral medication for 20 months without detectable HIV levels after undergoing stem cell transplant to treat cancer, but, unlike in previous cases, his donor stem cells did not have the mutation that confers resistance to HIV, said the researchers.

Dubbed the “Geneva patient”, the man was diagnosed with HIV in 1990 and had been on continuous antiretroviral suppression since 2005, reported Asier Sáez-Cirión, PhD, of Institut Pasteur in Paris.

When the patient was diagnosed with biphenotypic sarcoma in 2018, he had chemoradiation therapy followed by an allogeneic stem cell transplant from a donor who had wild-type CCR5.

MedPage Today reports that in his presentation at the biannual International AIDS Society (IAS) Conference on HIV Science last month, Sáez-Cirión said the Geneva patient had a difficult recovery, having to survive acute and chronic graft-versus-host disease as his native immune system tried to reject the transplant.

In November 2021, the patient elected to stop taking antiretroviral medication, and viable HIV has not been detected since then.

Dr Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, said in all five prior cases of durable HIV remission reported after receiving stem cell transplants, the donors had a mutation that knocks out the receptor CCR5 which HIV needs to enter a cell, the CCR5 Delta 32 mutation.

“In this case, the donor did not have a CCR5 deletion. He received a transplant from a donor who had normal wild-type stem cells, meaning those cells were susceptible to HIV infection,” she noted.

Lewin highlighted the “Boston patients”  first discussed in detail a decade ago at the IAS 2013 conference: “In these two cases, both men interrupted antiretroviral treatment, and unfortunately the first patient’s HIV rebounded four months after treatment interruption, and the second patient recurred at eight months.

“In this new case, the patient has already achieved far longer durable HIV remission without treatment than the Boston patients,” she said. “So this is promising. But we learned from the Boston patients that even a single virion can lead to viral rebound. With this particular individual, he will need to be watched closely over the next months to years.”

The prior potential HIV “cure” cases after stem cell transplant include:

• Timothy Brown, the initial “Berlin patient” who sparked hopes of a cure, who died 12 years after the transplant due to recurrence of cancer
• Adam Castillejo, “the “London patient, who has been off antiretroviral therapy for five years
• Marc Franke, the “Dusseldorf” patient, who has been off antiretroviral therapy for four years
• An unidentified New York patient off antiretroviral therapy for 2.5 years
• Paul Edmonds, the “City of Hope (California)” patient, who has been off antiretroviral therapy for two years since his transplant

In the case of the “Geneva patient”, no traces of antiretroviral drugs have been found in his blood from November 2021 to June 2023, except for two instances when he used on-demand pre-exposure prophylaxis.

In that same time period, he has had undetectable virus using an assay sensitive down to 20 copies per mL. Defective virus has been detected in his blood twice, and in his blood marrow on two occasions, but no intact HIV has been seen as he continues to have blood taken every two to three months.

Bone marrow analysis ceased 19 months after the transplant.

Replication competent HIV-1 was detected in samples before human stem cell transplant but not afterward, Sáez-Cirión said in his oral late-breaker presentation.

“Weak HIV DNA was detected post-transplant but all virologic markers became progressively undetectable. We cannot exclude that the virus is still present in anatomical or cellular sanctuaries. Immunological markers are consistent with absence of antigenic stimulation after antiretroviral interruption.”

While Lewin cautioned this is a case report, “case reports do help in many ways in work towards a cure for HIV”.

Study details

Absence of viral rebound for 18 months without antiretrovirals after allogeneic hematopoietic stem cell transplantation with wild-type CCR5 donor cells to treat a biphenotypic sarcoma

A. Sáez-Cirión, A. Mamez, A. Calmy, et al.

Presented at the International AIDS Society (IAS) Conference on HIV Science on 24 July 2023

Background
Durable HIV-1 remission after antiretroviral treatment (ART) discontinuation has been reported for 5 individuals receiving allogeneic haematopoietic stem cell transplant (aHSCT) from CCR5?32 homozygous donors. We report here a Caucasian male (Icistem-34), diagnosed with HIV-1 in 1990 and on continuous suppressive-ART since 2005. In 2018, he received chemotherapy followed by aHSCT from an unrelated HLA-matched (9/10) wild-type CCR5 donor to treat a biphenotypic sarcoma. ART was discontinued in November 2021. His viral load has remained undetectable for 18 months so far.


Methods
Samples, pre-aHSCT, pre and/or post treatment interruption (TI), were analysed for HIV RNA, HIV DNA, antiretrovirals, HIV-1 antibodies, NK and T cells phenotype, and HIV/CMV T-cell responses. Intact proviral DNA analyses (IPDA), tests of viral production by purified CD4+ T cells and their susceptibility to HIV were performed post-aHSCT.


Results
Ultrasensitive HIV RNA (4 copies/ml) and HIV DNA (457 and 1096 copies/million CD4 cells in blood and bone marrow) were detected before aHSCT. The virus was predicted R5. Full chimerism was achieved within a month post-aHSCT. Acute hepatic graft vs host diseases (GVHD) occurred soon after aHSCT, and was treated with corticosteroid/calcineurin inhibitor. Chronic hepatic GVHD occurred 8m after aHSCT and was treated with ruxolitinib, which was transiently discontinued but had to be resumed due to GVHD relapse. Standard plasma viremia remained undetectable after aHSCT, ultrasensitive RNA dropped to undetectable values. Proviral DNA also decreased significantly, despite low levels (4 to 40 copies/million cells) being detected sporadically post-aHSCT, including defective but not intact HIV DNA by IPDA. No virus was amplified from in vitro stimulated CD4+ T cells post-TI. Cells remained susceptible to HIV-1 in vitro. ART levels were undetectable post-TI except coinciding with two episodes of event-driven “PreP” (4 pills) at M2 and M12 post-TI. HIV-1 antibodies slightly declined since aHSCT. No HIV-specific T cell responses were detected post-TI.

Conclusions
We report an individual with HIV-1 who at 18m post-TI, 57m post-aHSCT with cells from a wild-type CCR5 donor, has no evidence of HIV-1 RNA rebound or replicating virus. These results suggest that HIV remission could be achieved in some cases in the context of aHSCT with wild-type CCR5.

 

International Aids Conference abstract – Absence of viral rebound for 18 months without antiretrovirals after allogeneic hematopoietic stem cell transplantation with wild-type CCR5 donor cells to treat a biphenotypic sarcoma (Open access)

 

MedPage Today article – Another HIV Patient Possibly Cured With Stem Cell Transplant (Open access)

 

See more from MedicalBrief archives:

 

Third patient HIV-free after virus-resistant cell transplant

 

Fourth person cured of HIV, fifth success in the wings: AIDS 2022 conference

 

UK man the second to be cleared of the Aids virus

 

‘Berlin Patient’ patient speaks in Cape Town on HIV cure research

 

 

 

 

 

 

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