March 3, 2024

A European man could be cured of HIV thanks to a stem cell transplant for a blood cancer

A European man has been in remission from HIV infection for nearly two years after receiving a stem cell transplant to treat blood cancer. If enough time passes without any signs of a viable virus, he could join the rarefied club of five people who are considered to be certain or possibly cured of HIV.

All six had HIV when they received a stem cell transplant to treat a blood cancer such as leukemia or lymphoma. But unlike the other five cases, this new one involved someone 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 AIDS Society’s International Conference on HIV Science in Brisbane, Australia. This biennial gathering of scientists will also hear significant presentations on post-treatment control of HIV in infant boys, the impact of circumcision on HIV risk in gay men, and the relationship between HIV and mpox (formerly known as mumps).

It remains unethical for a person with HIV who does not already qualify for a cancer stem cell transplant to undergo such treatment in the hope of curing the virus, given the significant toxicity of such treatment. Scientists generally expect any success in the effort to develop a widespread, scalable HIV cure therapy to take many years.

However, Dr. Sharon Lewin, president of the IAS and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, the new case of viral remission as “great news.” Such case reports, she said, “help in many ways the work toward a cure.”

‘Geneva Patient’

The man in remission from HIV will henceforth be known as the Geneva Patient, after the city in Switzerland where he received his treatment. He is in his early 50s, was diagnosed with the virus in 1990 and started taking antiretroviral treatment in 2005. In 2018, he was diagnosed with a rare blood cancer called extramedullary myeloid tumors. He was treated with radiation, chemotherapy and a stem cell transplant.

A research team led by Asier Sáez-Cirión, head of the viral reservoir and immune control unit at the Institut Pasteur in Paris, has overseen his case.

HIV is extremely difficult to cure. This is largely because even when suppressed by antiretrovirals, the virus hides in non-replicating immune cells, collectively known 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 those cells that have recently been infected, and it can take months or even years for each of them to return to a replicative state.

Since it was the first such case Announced in 2008, through there certainly were people cured and two additional people, pending more time to elapse without viral relapse, at you perhaps was a cure for HIV.

Before the case of the Geneva Patient, a handful of other people with HIV who developed cancer received stem cell transplants from donors without the rare genetic mutation that confers natural resistance to the virus. But no one from this group went more than 10 months after stopping antiretroviral treatment without virus resurgence. The hopes that they were cured were dashed.

The man in Switzerland has now spent 20 months without any viral rebound, after being removed from antiretrovirals in November 2021. Sáez-Cirión and his colleagues followed a battery of ultrasensitive tests in search of HIV in his body and were only able to detect trace amounts of the defective virus. But they still cannot rule out that the man keeps even one cell infected with a viable virus, one that could spring into action at any time and repopulate the body with HIV.

“The possibility of viral recovery is indeed a cause for concern,” said Sáez-Cirión. “The virus may survive in rare infected blood cells or in anatomical sites that we have not analyzed.”

It remains unclear why the Geneva Patient’s case has been so successful, at least so far, while others who have received similar treatment have not been so lucky.

Dr. Steven Deeks, a leading HIV cure researcher at the University of California, San Francisco, who was not involved in the Geneva Patient study, said in the details of the case “maybe what we once thought was impossible could be done.”

Speculating on the drivers of this man’s long HIV remission, Deeks said, “Elimination of most of the reservoir with chemotherapy was definitely the primary 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 result of stem cell transplants. This could also play a critical role, Deeks said, “because the newly formed immune system may have been attacking and clearing the old immune system, including any residual HIV-sustaining T cells.”

Sáez-Cirión said it is also possible that the immunosuppressive drugs that the Geneva patient still receives to prevent graft-versus-host disease may be preventing any residual HIV from replicating.

Post-treatment control of HIV

Researchers in sub-Saharan Africa identified a handful of boys born with HIV who did not experience viral rebound even after stopping their antiretroviral treatment for long periods.

This finding comes from a study of 281 mothers in South Africa whose newborns contracted HIV. All infants were placed on antiretrovirals immediately after birth. But the investigators eventually found that the caretakers of five boys did not provide them with HIV treatment for periods of between three and 10 months, and yet each child had an undetectable or very low viral load.

Four of the boys were immediately put back on HIV treatment. However, one person remained on treatment and has now gone 19 months without a viral rebound. Three of the others are enrolled in a study where their treatment will be interrupted again, 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 boys can be classified as so-called post-treatment HIV controllers, because they had an undetectable viral load for more than six months while off antiretrovirals.

Before their presentation at the conference, however, Cromhout and her colleagues did not perform any ultra-sensitive tests to look for the residual presence of HIV in the children’s bodies. Such tests are underway.

Dr. Deborah Persaud, a pediatric infectious disease specialist at the Johns Hopkins University School of Medicine and head of a major ongoing study that seeks to cure HIV in infants, “This is a huge advance for the field of HIV remission and cure.” However, Persaud, who was not involved in the South African study, said that to support his findings, the study’s investigators would have to present data at the conference confirming that the five boys were infected and had indeed been off antiretrovirals for long periods – data that Cromhout confirmed to her team.

Risk of circumcision and HIV

In the mid-2000s, a dry of random controlled trials in sub-Saharan Africa it was found that circumcised men reduced the risk of female-to-male transmission of HIV by approximately 50% to 60%.

Now, a research team in China is the first to conduct such a study on gay and bisexual men. They enrolled about 250 uncircumcised men who have sex with men who reported primarily being the inserted partner in intercourse (referred to as the “top”). Half were randomly selected to be circumcised. After one year, five study participants got HIV, all in the control group. The study did not register any significant differences in sexual behaviors between the two study groups that could influence the relative HIV risk of men.

The difference in the rate of HIV acquisition between the two study groups, as calculated by the investigators, was statistically significant.

In a media call on Wednesday, Dr. Huachun Zou, a professor of epidemiology at Sun Yat-sen University’s School of Public Health in Shenzhen, China, said that more studies may be needed to fully determine whether circumcision reduces the risk of HIV among gay and bisexual men. But he said it is “very likely” that researchers will indeed conduct such research because of the global popularity of the HIV prevention pill, known as PrEP, as a way to reduce the risk of the virus among gay and bi men. He said PrEP is not widely used, however, 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 for 82,290 mpox cases from 2022. There was information on the HIV status of 39% of those people, and among them 52% had that virus – 16,633 people, or 20% of the total.

​​​​The study found that, overall, HIV was not associated with a greater likelihood of being hospitalized with mpox. However, being immunocompromised, including from HIV or another factor, was associated with about two to four times the risk of hospitalization, compared to 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 it was found that people with HIV had a very high risk of dying from mpox if their immune system was suppressed.

People with HIV who are treated with antiretrovirals can maintain fundamentally healthy immune systems.

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