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“A miracle of the human immune system”, it is in these terms that Dr. Xu Yu, an immunologist at the Ragon Institute in Boston, describes the case of a young woman diagnosed with HIV in 2013, now cured of the disease. have received any treatment: she and her team were unable to find viable HIV in this woman’s body, even after using highly sophisticated and sensitive tests to scan more than a billion of her cells. This is the second documented case of a sterilizing cure that relies solely on the natural immunity of the patient.
Dr. Yu is also the lead author of a study published in Nature in August 2020, the purpose of which was to examine a sample of individuals with spontaneous control of HIV-1, dubbed “the elite controllers.” These people are among less than 0.5% of HIV positive people whose immune system is somehow able to reduce virus replication to very low levels without antiretroviral drugs.
This second case of “sterilizing cure” is the subject of an article in the Annals of Internal Medicine. The mechanisms that led to the total elimination of the virus in this young woman remain to be known. “How can this happen? And how can we reproduce this therapeutically in everyone? Asks Dr. Steven Deeks, an HIV specialist at the University of California, San Francisco, who was not involved in the study. These special cases of recovery provide hope to the approximately 38 million people living with HIV worldwide.
No intact viral sequence in more than 1 billion cells
HIV is particularly difficult to remove from the body, because during infection, this virus places copies of its genome in the DNA of cells, creating what is called a “viral reservoir” in which it becomes infected. It is immune to drugs and the body is immune system. New virus particles are constantly forming from this reservoir. Antiretroviral drugs can prevent the production of new viruses, but they cannot remove the reservoir; that is why infected people must take daily treatment to suppress the virus.
In “elite controllers”, the situation is different: viral reservoirs are still present in the body and can produce more virus, but the T cells of your immune system can suppress the virus on their own. need for any treatment! In their previous study, Yu and his colleagues found that the immune system of these individuals appeared to have preferentially destroyed infected cells capable of producing new viable copies of the virus; only infected cells remained in which the viral genetic code had been assembled in a kind of “dead zone” of cellular DNA and, therefore, could not replicate.
One of the patients in the study cohort, Loreen Willenberg, a 67-year-old Californian who was diagnosed with HIV in 1992, stood out from the crowd for her immune system, which apparently wiped out the virus altogether. Even after sequencing billions of their cells, the scientists could not find any intact viral sequences. The patient in question today, a 30-year-old Argentine, was first diagnosed with HIV in 2013 and exhibits fairly similar immune prowess.
Yu’s team looked for traces of viable HIV in 1.2 billion of her blood cells and then 500 million cells of placental tissue after she gave birth to an HIV-negative baby in March 2020. Even with sequencing techniques More sophisticated, the researchers once again found no intact viral sequences in this “elite controller” patient.
Particularly powerful T lymphocytes
Their study establishes that the patient does not have proviral DNA capable of replicating in her cells. Dr. Yu speculated that each of these women may have developed a particularly potent killer T-cell response – complete immune pressure – that researchers may one day replicate in the form of drug therapy. The identification of this second case suggests, in any case, that it may be possible to develop a sterilization therapy.
There are also a number of documented cases of people who, after stopping their antiretroviral therapy, have not seen their viral load recover for years, particularly if the therapy was started shortly after contracting the virus. Today, scientists are trying to cure HIV infection in various ways, including gene therapy; Some methods aim to remove the virus from its reservoir, others involve blocking it forever in cells.
To date, researchers have successfully cured two other people with complex stem cell transplants. An American, Timothy Ray Brown, and a Londoner, Adam Castillejo, received stem cell transplants to treat a cancer they had simultaneously (acute myeloid leukemia and Hodgkin’s lymphoma, respectively). The donors had a rare genetic defect that made their immune cells resistant to HIV. But this approach is considered too dangerous to try to eliminate HIV in a person who also does not have a treatable cancer through a stem cell transplant.
Scientists are also trying to develop vaccines to enhance the body’s immune response to the virus. Moderna’s laboratory has also just launched a clinical trial of a messenger RNA vaccine against AIDS; the results of the first phase are expected in 2023. Currently, 38 million people in the world are living with the AIDS virus and there are two million new patients. every year. According to the WHO, in 2020, 680,000 people died from the disease.
Annals of Internal Medicine, G. Turk et al.
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