乌鸦传媒

BRISBANE, Australia -- Another HIV patient has been off antiretroviral medication for 20 months without detectable HIV levels after he underwent stem cell transplant to treat cancer -- but, unlike previous "cures," this patient's donor stem cells did not have the mutation that confers resistance to HIV.

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 underwent chemoradiation therapy and then had an allogeneic stem cell transplant from a donor who had wild-type CCR5, he said.

In his presentation at the biannual International AIDS Society (IAS) Conference on HIV Science, 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.

"Now, this is great news," commented Sharon Lewin, MD, director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia.

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 that HIV needs to enter a cell, the CCR5 Delta 32 mutation, she noted at a press conference.

"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 that those cells were susceptible to HIV infection," she said.

Lewin pointed to 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 4 months after treatment interruption, and the second patient recurred at 8 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 5 years
• Marc Franke, the "Dusseldorf" patient, who has been off antiretroviral therapy for 4 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 2 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 through June 2023, except for two instances when the patient 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 on two occasions and in his blood marrow on two occasions, but no intact HIV has been seen as he continues to have blood taken every 2 to 3 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 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."

Comment