A German man has probably been cured of HIV, a medical milestone reached by only six other people since the start of the AIDS epidemic more than 40 years ago.
The German, who prefers to remain anonymous, was treated for acute myeloid leukemia (AML) with a stem cell transplant in October 2015. He stopped taking his antiretroviral drugs in September 2018 and remains in viral remission with no rebound. Multiple highly sensitive tests have detected no viable HIV in his body.
In a statement, the man said of his remission: “A healthy person has many wishes, a sick person has only one.”
The case, which investigators say offers key lessons for HIV treatment research, is scheduled to be presented Wednesday by Dr. Christian Gaebler, a physician-researcher at Charité-Universitätsmedizin in Berlin, at the 25th International AIDS Conference in Munich.
“The more we see these HIV remissions without any HIV treatment, the more confident we can be that we are probably looking at a case where we have actually eradicated all competent HIV,” Gaebler said.
As with all previous cases of potential HIV cures, experts are keen to temper public enthusiasm with one caveat: The treatment that apparently thwarted the virus in all seven patients will be available only to a select few. All contracted HIV and later developed blood cancers, requiring stem cell transplants to treat the malignancy.
The transplants — in most cases from donors selected for their immune cells, the cells targeted by HIV — had a rare natural resistance to the virus and helped eradicate apparently all viable or competent copies of the virus from the body.
Stem cell transplants are highly toxic and can be fatal, so it would be unethical to offer them to people with HIV, except to treat distinct diseases, such as blood cancer.
HIV is extremely difficult to cure because some of the infected cells are long-lived immune cells that are dormant or enter a dormant state. Standard antiretroviral treatment for HIV only works on immune cells that, like infected cells, are actively making new copies of the virus. As a result, HIV in resting cells remains under the radar. Collectively, these cells are known as the viral reservoir.
At any time, a reservoir cell can start producing HIV. That’s why if people infected with the virus stop taking their antiretrovirals, their viral load usually rebounds within a few weeks.
A stem cell transplant has the potential to cure HIV in part because it requires destroying the immune system of a person with cancer through chemotherapy and sometimes radiation and replacing it with a healthy immune system from a donor.
In five of the seven cases of permanent or possible cure of HIV, doctors found donors who had rare natural defects in both copies of a gene that gives rise to a special protein, called CCR5, on the surface of immune cells. Most strains of HIV attach to this protein. protein to infect cells. Without functional CCR5 proteins, immune cells are resistant to HIV.
The German’s donor had only one copy of the CCR5 gene, meaning his immune cells probably have about half the normal amount of this protein. Additionally, he had only one copy of the gene. Together, these two genetic factors may have increased his chances of recovery, Gaebler said.
Although having two copies of the defective CCR5 gene is rare (occurring in about 1% of people of Northern European descent), having only one copy occurs in about 16% of these people.
“So the study suggests that we can expand the donor pool for these kinds of cases,” Dr. Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, said at a news briefing last week.
Interestingly, a man treated in Geneva and announced last year to be cured of HIV had a donor with two normal copies of the CCR5 gene. The transplanted immune cells were therefore not resistant to HIV.
These two recent European cases raise crucial questions about what factors actually contribute to successful HIV treatment.
“The level of protection that one would expect from a transplant should not have been enough to prevent the virus from surviving and bouncing back,” Dr. Steven Deeks, a leading HIV treatment researcher at the University of California, San Francisco, who is not involved in German’s care, said of his case. “There are several testable theories, so I’m optimistic that we’ll learn something here that could shape the next generation of treatment studies.”
Gaebler said having HIV-resistant immune cells in the mix greatly improves the chances of a successful stem cell transplant. But the absence of that safety net, or the presence of a safety net with holes, as in the German’s case, does not preclude success.
“We need to understand how the new immune system managed to get into his body and how it managed to eliminate the HIV reservoirs over time,” he said. Suggesting that the transplanted immune cells were able to attack the viral reservoir, he added: “The donor’s innate immune system may have played an important role here.”
The other 6 cured or potentially cured of HIV
All were initially known by pseudonyms depending on where they were treated.
- Timothy Ray Brown, aka the “Berlin Patient.” Brown, an American living in Germany, was treated for AML. When his case was announced in 2008, it galvanized the field of HIV research. Born in 1966, he was cured of HIV but died of recurrent leukemia in 2020.
- Adam Castillejo, aka the “London Patient.” Castillejo, a 44-year-old Venezuelan living in England, received a stem cell transplant for AML in 2016 and stopped his HIV treatment in 2017. He is considered cured.
- Marc Franke, the “Patient from Düsseldorf.” Treated with a stem cell transplant for AML in 2013, Franke, 55, stopped antiretroviral treatment in November 2018 and is considered cured.
- Paul Edmonds, aka the “City of Hope patient.” Edmonds, the oldest potential cure at 63 when he received a stem cell transplant for AML in 2019, has been receiving reduced-intensity chemotherapy due to his age. Off antiretrovirals since March 2021, he will be considered cured when he reaches five years without a viral rebound. In an interview, he expressed excitement about the new case of a man who is also likely cured, saying, “My vision is clear: a world where HIV is no longer a sentence, but a footnote in history.”
- THE “New York patient.” The first woman and person of mixed race to be cured, she was diagnosed with leukemia in 2017 and received a stem cell transplant augmented with umbilical cord blood, which allowed for a weaker genetic match with her donor, thereby expanding the donor pool.
- The “Geneva patient.” In his fifties, he was diagnosed with a rare blood cancer in 2018 and has not been receiving HIV treatment since November 2021. Researchers remain cautious about his cured status, as his immune cells are not resistant to HIV.
Franke, Edmonds and Castillejo, who have become friends, are expected to attend the HIV conference in Munich.