Two new cases of functional HIV cure

A new case of recovery and a case of durable functional remission were presented at the International Conference on HIV/AIDS 2022 in Montreal.

The first, nicknamed the “City of Hope Patient” after the Los Angeles Cancer Center where he received his transplant 3 and a half years ago, is a 66-year-old American man, HIV positive Refers to a subject whose serum contains specific antibodies directed against an infectious agent (toxoplasma, rubella, CMV, HIV, HBV, HCV). Term used, in everyday language, to designate a person living with HIV. au HIV Human immunodeficiency virus. In English: HIV (Human Immunodeficiency Virus). Isolated in 1983 at the Pasteur Institute in Paris; recently discovered (2008) rewarded with the Nobel Prize in Medicine awarded to Luc Montagnier and Françoise Barré-Sinoussi. since 1988, who underwent a bone marrow transplant to treat his acute myeloid leukemia (AML), declared in 2018.

This approach has already been used successfully in 3 other people living with HIV at the time of the transplant. The idea is to use stem cells from a donor carrying a genetic mutation giving him a natural resistance to HIV. Thus, the doctors decided to stop taking antiretrovirals two years after his transplant and this new patient has not had any specific treatment for HIV for 17 months.

The first case of functional cure had been presented in November 2008. Timothy Ray Brown, first known as “the Berlin patient”, had thus become the first person to be cured of HIV following a bone marrow transplant. He died in 2020 twelve years later, from leukemia, without a trace of HIV ever being found in his body.

Although important for the patient, and scientifically, this therapeutic solution is too complicated and dangerous to be used on a large scale and is only offered to people who already have a serious health problem requiring a bone marrow transplant (usually , leukemia).

Another path to remission

The second case presented is that of a functional remission: This is that of a 59-year-old Spanish woman – nicknamed the patient from Barcelona – who benefited in 2006 from an innovative treatment to strengthen the immune response. His antiretroviral treatment was indeed interrupted after having benefited for 11 months from four drugs intended to prime the immune system to better fight the virus. Fifteen years later, her immune system alone controls the replication of HIV and the patient is therefore considered to be in remission.

This woman had been diagnosed during her primo-infection First contact of an infectious agent with a living organism. Primary infection is a key moment in diagnosis and prevention because the HIV viral loads observed during this period are extremely high. This is a period when the person infected with HIV is very contaminating. Historically, it has been shown that what contributed, in the 1980s, to the HIV epidemic in certain large American cities such as San Francisco, was not only risky practices but also the fact that many people were in same time at the primary infection stage., before HIV settles too deeply in the reservoirs. She quickly joined a small clinical trial testing immunomodulatory therapies, in which she initially received standard antiretroviral therapy of lopinavir/ritonavir, tenofovir disoproxil fumarate and lamivudine for nine months plus a short course of cyclosporine A (an immunosuppressive drug). Then his treatment was suspended for a while and granulocyte-macrophage colony-stimulating factor (an agent that stimulates the production of white blood cells) and interferon-alpha (a cytokine produced by the innate immune system in response to environmental exposures, including viral infections.) were used.

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The situation is slightly different from transplant patients since HIV is still present in the body of the person, it has not been eradicated but it is controlled thanks to the action of his memory NK cells and his gamma-delta CD8 T lymphocytes. . These control mechanisms are different from those already seen in ‘elite controllers’, those people living with HIV (about 1 in 200) whose immune systems can control the virus without treatment. (She also experienced an acute phase of primary infection.)

Further studies will be needed to understand the success of this new therapy in this patient. Researchers do not currently know if this therapeutic strategy is applicable to other people living with HIV. It also failed in all the other participants in the initial trial.

These successes, while important to the advancement of HIV eradication research, should not cause us to lose our temper. First, for these few successes, these strategies have experienced dozens of failures. And faced with this handful of cures and functional remissions, there are still 38 million people who are waiting for a definitive cure for their HIV infection.

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