A sixth person with HIV, being referred to as the Geneva patient, has likely been cured of HIV after receiving a stem cell transplant for leukaemia. The level of virus in his blood remained undetectable 20 months after his antiretroviral therapy was discontinued.

What is interesting, however, is that in this case his donor did not have the gene mutation that the researchers had specifically selected for in all five previous cases. The mutation is associated with lower risk of contracting the infection.

What do we know about the Geneva patient?

The Geneva patient had been living with HIV since the 1990s and underwent a stem cell transplant in 2018 for an aggressive form of leukaemia. One month after the transplant, his doctors found that there was a significant reduction in the number of HIV-infected cells. Seeing this, the doctors tapered off his medicines and completely stopped them in November 2021. Twenty months later, his tests did not find any viral particles, latent reservoirs of the infection, or elevated immune response against the virus, according to Institut Pasteur, which is examining the case along with Institut Cochin and the IciStem consortium.

Unlike the five previous HIV cases of remission, however, the Geneva patient’s cells continue to be susceptible to HIV. This is the reason the researchers cannot rule out the possibility of his HIV returning. “Through this unique situation, we are exploring new avenues in the hope that HIV remission or even cure will one day no longer be a one-off occurrence,” said Alexandra Calmy, HIV/AIDS Unit Director at the Geneva University Hospitals in a release.

What is the genetic mutation that was selected for the other patients in HIV remission?

All the six patients who have achieved HIV remission so far needed the stem cell transplantation for treatment of their cancers. In the first five cases, however, the treatment teams specifically looked for donors with CCR5 delta 32 mutation that is associated with lower risk of HIV.

HIV lowers immunity in infected individuals by attacking the CD4 immune cells. However, to gain entry into these cells, it needs receptors on the surface. People who inherit the CCR5 delta 32 mutation from both sets of parents do not form these receptors, essentially locking the virus out of the cells. Those who inherit the mutation from one of the parents have fewer receptors and are less likely to get the infection.

Only 1 per cent of the people in the world carry two copies of the CCR5-delta 32 mutation – meaning they got it from both their parents — and another 20 per cent carry one copy of the mutation, mainly those of European descent.

Can stem cell transplant become routine treatment for HIV?

It is highly unlikely. There are 38.4 million people living with HIV currently and it would be impossible to find a matching donor for all of them. In addition, the CCR5 delta 32 mutation mainly occurs in Caucasians, meaning it would not be possible to find donors for patients from high-burden countries, mainly in Africa. Besides, stem cell transplantation is a major procedure and comes with its own risks, including the risk of the patient rejecting the donor cells. Even with the transplants, the virus may learn to infect cells through other mechanisms.

Instead, treatment of HIV across the world depends on effective antiretroviral therapy. These cocktails suppress the replication of the virus within the body, allowing the number of CD4 immune cells to bounce back. It also reduces the viral particles to undetectable levels, meaning the person can no longer transmit the infection to others.

However, the anti-retroviral therapy needs to be taken for life. It doesn’t remove the virus completely from the body, meaning the viral count goes up again whenever therapy is stopped. The drugs also prevent the progression to the Acquired Immunodeficiency Syndrome (AIDS) stage.

Who are the patients who have become HIV-free so far?

Timothy Ray Brown, initially referred to as the Berlin patient, became the first person to overcome HIV after two stem cell transplants in 2007 and 2008. He remained HIV free till his death due to cancer in 2020.

Researchers finally replicated the success seen with the Berlin patient in 2019 when the London patient Adam Castillejo was announced to be virus-free. Two cases of ‘The City of Hope patient’ and ‘New York patient’ were reported in 2022.

The New York patient became the first mixed-race individual to be free of HIV after stem cell transplantation with CCR5 delta 32 mutation. The transplant was done using a dual stem cell therapy – using stem cells from umbilical cord of a neonate, complemented with stem cells from an adult – that requires less restrictive HLA matching. This may make such transplants possible in people from other races as well.

The results of the Dusseldorf patient were announced earlier this year. A 53-year-old man from Germany remained free of the virus four years after stopping antiretroviral therapy.
News Source: Indianexpress