A European man has been in a state of remission from HIV infection for nearly two years after receiving a stem cell transplant to treat blood cancer. If enough time passes with no signs of viable virus, he could join the rarefied club of five people who are considered either definitely or possibly cured of HIV.
All six individuals had HIV when they received stem cell transplants to treat blood cancers such as leukemia or lymphoma. But unlike the five other cases, this new one involves a person whose donor did not have a rare genetic abnormality that generates resistance to HIV in the immune cells that the virus targets for infection.
The man’s case will be presented next week at the International AIDS Society Conference on HIV Science in Brisbane, Australia. This major biennial gathering of scientists will also hear noteworthy presentations regarding post-treatment control of HIV in infant boys, circumcision’s impact on HIV risk in gay men, and the relationship between HIV and mpox (formerly known as monkeypox).
It remains unethical for a person with HIV who does not already qualify for a stem cell transplant due to cancer to undergo such a treatment in hopes of curing the virus, given such treatment’s considerable toxicity. Scientists generally expect that any success in the effort to develop a widely scalable HIV cure therapy will likely take decades.
Nevertheless, Dr. Sharon Lewin, president of the IAS and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, called the new viral remission case “great news.” Such case reports, she said, “help in many ways in the work toward a cure.”
The ‘Geneva Patient’
The man newly in remission from HIV has been dubbed the Geneva Patient, after the Swiss city where he has received his treatment. He is in his early 50s, was diagnosed with the virus in 1990 and began taking antiretroviral treatment in 2005. In 2018, he was diagnosed with a rare blood cancer known as an extramedullary myeloid tumor. He was treated with radiation, chemotherapy and a stem cell transplant.
His case has been overseen by a research team led by Asier Sáez-Cirión, head of the viral reservoirs and immune control unit at the Institut Pasteur in Paris.
HIV is vexingly difficult to cure. This is in large part because even when suppressed by antiretrovirals, the virus hides in nonreplicating immune cells, known collectively as the viral reservoir. Such standard HIV treatment only works on cells that are actively producing new viral copies. So the virus remains under the radar of antiretrovirals within these latently infected cells, each of which can take months or even years to return to a replicating state.
Since the first such case was announced in 2008, three people have definitely been cured and two additional people, pending more time passing without a viral rebound, have possibly been cured of HIV.
Prior to the Geneva Patient’s case, a handful of other people with HIV who developed cancer also received stem cell transplants from donors without the rare genetic mutation conferring natural resistance to the virus. But none from this group went more than 10 months after stopping antiretroviral treatment without a resurgent virus. Hopes that they had been cured were dashed.
The man in Switzerland has now spent 20 months with no viral rebound, having been taken off of antiretrovirals in November 2021. Sáez-Cirión and his colleagues have conducted a battery of ultrasensitive tests in search of HIV in his body and have only been able to detect trace amounts of defective virus. But they still cannot rule out that the man retains even a single cell infected with viable virus, one that could spring to action at any moment and repopulate the body with HIV.
“The possibility of viral rebound is indeed a concern,” Sáez-Cirión said. “The virus may persist in rare infected blood cells or anatomical sites that we have not analyzed.”
It remains unclear why the Geneva Patient’s case has been so successful, at least thus far, while others who received similar treatment were not so fortunate.
Dr. Steven Deeks, a leading HIV cure researcher at the University of California, San Francisco, who was not involved in the study of the Geneva Patient, said the details of the case “suggest that what we once assumed was impossible might in fact be possible.”
Speculating about the drivers of this man’s lengthy HIV remission, Deeks said, “Eliminating most if not all of the reservoir with chemotherapy was certainly the key intervention.” Deeks also noted the man’s repeated episodes of what is known as graft-versus-host disease, a powerful and potentially dangerous immune reaction that occurs as a consequence of a stem cell transplant. This might have also played a crucial role, Deeks said, “as the newly rebuilt immune system may have been attacking and clearing the old immune system, including any residual T cells harboring HIV.”
Sáez-Cirión said it is also possible that the immunosuppressive drugs that the Geneva Patient continues to receive to prevent graft-versus-host disease may be preventing any residual HIV from replicating.
Post-treatment control of HIV
Researchers in sub-Saharan Africa have identified a handful of boys born with HIV who did not experience viral rebound even after their antiretroviral treatment was interrupted for extended periods.
This finding comes from a study of 281 mothers in South Africa who had passed HIV to their newborns. The infants were all put on antiretrovirals immediately after birth. But the investigators eventually discovered that the caretakers of five boys had not provided them with HIV treatment for periods spanning three to 10 months, and yet each of these children maintained an undetectable or very low viral load.
Four of the boys were immediately put back on HIV treatment. However, one other has been kept off of treatment and has now passed 19 months without a viral rebound. Three of the others have been enrolled in a study in which their treatment will once again be interrupted, but under close monitoring.
Dr. Gabriela Cromhout, a research clinician and doctoral candidate at the University of KwaZulu-Natal and one of the lead authors of the study, said three of the boys can be classified as so-called post-treatment controllers of HIV, because they had sustained an undetectable viral load for more than six months while off antiretrovirals.
In advance of their conference presentation, Cromhout and her colleagues did not, however, conduct any ultrasensitive tests to search for the residual presence of HIV in the children’s bodies. Such tests are ongoing.
Dr. Deborah Persaud, a pediatric infectious disease specialist at the Johns Hopkins University School of Medicine and the head of a major ongoing study seeking to cure HIV in infants, said, “This is an enormous advance for the field of HIV remission and cure.” However, Persaud, who was not involved in the South African study, said to back their findings, the study’s investigators would need to present data at the conference confirming that the five boys were infected and that they were indeed off antiretrovirals for the extended periods — data that Cromhout confirmed her team has on hand.
Circumcision and HIV risk
In the mid-2000s, a trio of randomized controlled trials in sub-Saharan Africa determined that circumcising men reduced the risk of female-to-male sexual transmission of HIV by about 50% to 60%.
Now, a research team in China is the first to have completed such a study of gay and bisexual men. They enrolled about 250 uncircumcised men who have sex with men who reported primarily being the insertive partner in intercourse (known as being the “top”). Half were randomly selected to be circumcised. After one year, five study participants contracted HIV, all of them in the control group. The study registered no significant differences in sexual behaviors between the two study groups that might have impacted the men’s relative risk of HIV.
The difference in the HIV acquisition rate between the two study groups, the investigators calculated, was statistically significant.
At a media call on Wednesday, Dr. Huachun Zou, a professor of epidemiology at the Sun Yat-sen University School of Public Health in Shenzhen, China, said that larger studies may be necessary to fully establish whether circumcision reduces the risk of HIV among gay and bisexual men. But he said that it is “very unlikely” that researchers will indeed launch such research due to the global popularity of the HIV prevention pill, known as PrEP, as a means of reducing risk of the virus among gay and bi men. He said that PrEP is not, however, widely used in China, a nation that also has a low circumcision rate.
HIV and mpox hospitalization
This study looked at surveillance data from the World Health Organization regarding 82,290 mpox cases from 2022. There was information about the HIV status for 39% of these individuals, among whom 52% — 16,633 people, or 20% of the total — had that virus.
The study found that overall, having HIV was not associated with a greater likelihood of being hospitalized with mpox. However, being immunocompromised, including from HIV or from another factor, was tied to about two to four times the hospitalization risk, compared with being HIV-negative and having a healthy immune system.
Fifty-eight of the people with HIV died, as did four of the 15,371 people without HIV.
A paper published in The Lancet in February found that people with HIV had a very high risk of death from mpox if their immune system was suppressed.
People with HIV who are treated with antiretrovirals can maintain essentially healthy immune systems.
