66-year-old HIV patient of 31 years cured with stem cell transplant

• Living with HIV for 31 years, 66-year-old developed AML -- a type of blood cancer.
• In 2019, he received stem cell transplant from a volunteer donor with a rare genetic mutation.
• He has been HIV-free for 17 months now, without retroviral drugs.

A 66-year-old who was infected with the human immunodeficiency virus (HIV) in 1988 and lived with the disease for over three decades has been cured following a stem cell transplant.

HIV attacks the cells of the human immune system and, if left untreated, can lead to acquired immunodeficiency syndrome (AIDS), a condition without a cure. Current HIV treatments involve using retroviral drugs, which work by stopping the replication of the virus inside the cells. However, the treatment is lifelong; viral numbers can increase in the infected individual without medications.

Research institutes around the world are working to find treatment methods that can help infected individuals stay virus-free without the need to administer drugs on a daily basis. One of them is chimeric antigen receptor (CAR) T cells, which can selectively target the cells in the host infected with HIV, stopping the virus in its tracks. The other is to take away the cells that the virus usually targets in the body.

A mutation that makes a world of difference

CCR5 is a receptor on a type of immune cell that HIV targets to make its way inside the immune system. In some individuals though, a mutation called delta 32 on the gene that codes for the CCR5 protein results in a receptor that is immune to an HIV attack. Without an entry into the immune system, the virus cannot replicate in the body.

Researchers at the City of Hope cancer research center in Los Angeles have been using the advantage gained by this mutation to treat people who have HIV. By transplanting stem cells from a donor who has the delta-32 mutation on the CCR5 gene into an infected individual, they can replace the recipient's immune cells with those that are resistant to HIV infection.

The method has been used before to treat three other individuals, including a woman. However, the recent case involves the oldest patient yet.

The not-so-straightforward transplant

A stem cell transplant is not an easy procedure to operate. In the case of the 66-year-old, it was further complicated due to the fact that he had developed acute myelogenous leukemia (AML), a type of blood cancer that is commonly seen in people who have lived long with HIV, a press release said.

To prepare for the transplant, clinicians put the patient through three chemotherapies to get him into remission. This was less intensive chemotherapy that the City of Hope team has developed for older or less fit patients scheduled for transplant. He received this transplant three years ago, following which he continued his retroviral treatment till March 2021, when the research team confirmed that he could stop taking the medications.

Following that, the patient has been monitored closely for over 17 months but hasn't shown any sign of the virus in his blood or tissue samples.

"This patient was the oldest to receive a stem cell transplant [of the four patients], has lived the longest with HIV prior to his transplant, and received the least immunosuppressive therapy, we now have evidence that if the right stem cell donor is found for patients living with HIV who develop blood cancers, we can use newer and less intensive chemotherapy regimen options to try to achieve a dual remission," said Jana. K Dickter, associate clinical professor at City of Hope. "This may open up whole new opportunities for older patients living with HIV and blood cancer.”