麻豆传媒

MONTREAL – A man who held a record of sorts in living with HIV infection is now one of a handful of individuals in the world to have achieved a functional cure of the disease which causes AIDS as well as remission from acute leukemia, researchers reported here.

The so-called "City of Hope patient" is a 66-year-old man who was first diagnosed with an AIDS-defining illness in 1988 and then was diagnosed with acute leukemia in 2019, according to Jana Dickter, MD, infectious disease specialist at the City of Hope Medical Center in Duarte, California, speaking at the 2022 .

Dickter said that when treatment for leukemia required stem cell transplant, doctors sought a donor who possessed the HIV-resistant CCR5 homozygous delta mutation.

She said the patient received his blood stem cell transplantation 3.5 years ago and has been off antiretroviral therapy for 17 months without any evidence of HIV replication in his body. "His acute leukemia also remains in complete remission," she said.

"This patient's experience is unique from the three previous patients who were treated with stem cell transplants for their respective blood cancers and then achieved remission from HIV," Dickter added. "At the age of 63, he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions. He had been living with HIV the longest of any person, too – more than 31 years, prior to transplant."

But, the City of Hope patient wasn't the only person discussed who has been off treatment for years without HIV rebound discussed at the press conference.

Nuria Climent, PhD, a research scientist at J.M. Miro Hospital Clinic at the University of Barcelona, detailed her "Barcelona patient" – a 59-year-old woman with sexually-acquired HIV who participated in a clinical trial in which different strategies for HIV control were attempted among individuals who were acutely-infected with HIV.

"Although ART [antiretroviral therapy] is effective in suppressing viral replication, HIV persists in reservoirs and rebounds after stopping therapy," she reported. "However, there are few patients, such as post-treatment controllers, who are able to maintain viral loads below detection limits without antiretroviral, being a realistic model for the HIV-functional-cure."

The Barcelona patient, she reported, has maintained HIV viral control after being off treatment for more than 15 years. Climent said that at the time of her early infection, researchers were able to culture virus from her blood. Her blood cells, which should have been susceptible to HIV invasion, showed a natural resistance to the virus. Climent suggested that analysis of the natural killer cells and CD8 T-cells might show clues that could be used in future treatments. "Strategies able to expand these cells could help to achieve HIV-functional-cure," she said.

"A cure remains the Holy Grail of HIV research," said Sharon Lewin, MD, PhD, International AIDS Society president-elect and professor of medicine at the University of Melbourne in Australia. "We have seen a handful of individual cure cases before, and the two presented here provide continued hope for people living with HIV and inspiration for the scientific community. The City of Hope patient is the oldest patient, and has had HIV the longest before his current treatment."

"What's more, we are now seeing an advance in the great challenge of finding a biomarker for the HIV reservoir – a truly exciting development," she said.

In commenting on her City of Hope patient, Dickter said he appears to have benefitted from circumstances surrounding his stem cell transplant: the donor cells contained the CCR5 delta32 mutation, and he received a less intensive chemotherapy regimen that City of Hope developed for older and less fit patients that makes them more likely to accept allogeneic stem cells for treatment of blood cancers.

"This experience gives hope that some patients may not need fully intensive chemotherapy to receive stem cell transplantation in order to put them into remission from HIV and leukemia," Dickter said. "This is important because due to advances in HIV therapy, people with HIV tend to be living longer."

These patients are among at least five individuals in the world who have achieved long-term remission from HIV. Two other patients include the Berlin patient, the London patient, and the Brazil patient.

The Berlin patient died after a recurrence of leukemia. He had been HIV-free for about 15 years. The London patient has been HIV-free for about 4 years since stopping antiretrovirals and is still doing well. A Brazil patient was in remission for more than 15 months before his viral load once again increased in summer 2020.

Since 1981, the date at which most people cite as the start of the HIV epidemic, more than 50 million people have been infected with HIV worldwide.