2023-05-10 20:00:00
These rare cases, known as ‘after-treatment controllers’, generated more autologous neutralizing antibodies, exerting greater selective pressure on the virus.
People who contract the AIDS virus (HIV) must take lifelong treatment with antiretroviral drugs to keep the infection at bay and avoid transmitting it to other people. However, in some patients the virus does not reappear when treatment is stopped. Those minority cases are known among researchers in the field as aftertreatment controllersand its study is essential to find clues that can, in the future, advance in curative treatments of the infection.
Post-treatment controllers are patients who start antiretroviral therapy very early and whose immune system is capable of control the infection by itself when treatment is discontinued. A recent example is the case of the patient from Barcelona who, after more than 15 years of suspending antiretroviral medication, has maintained autonomous control of HIV replication, presented at the World AIDS Conference in Montreal last July. .
Today is published in Science Translational Medicine more information about the immunological characteristics of this type of patients. The research, whose first signatory is Elmira Esmaeilzadeh, a scientist in the laboratory of virologist Jonathan Li, at Brigham and Women’s Hospital and Harvard University, in Boston, focuses on the antibodies of these individuals.
Scientists have compared six post-treatment controllers and six other patients who discontinued therapy without getting to control the virus. When examining plasma samples, they saw more autologous neutralizing antibodies in the controllers, as well as less genetic diversity of the virus, which contributed to these antibodies exerting greater selective pressure on HIV.
The researcher at the Seville Institute of Biomedicine (IBiS) at the Virgen del Roco University Hospital, Ezequiel Ruiz-Mateos Carmona, points out that “normally, neutralizing autologous antibodies fade quickly and fail to control the virus, but in this study they observe that with treatment the antibodies mature until they are effective against the virus”. The expert from the AIDS Study Group (Gesida) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Seimc) highlights the study that shows how “antibodies exert a greater neutralization force in post-treatment controllers. In addition, this is associates that the viral sequences are more homogeneous, from which it can be inferred that the presence of neutralizing autologous antibodies with greater viral inhibition capacity is associated with more pathogen containment and, therefore, less replication capacity and diversity”.
These traits combined may constitute “a biomarker that indicates in patients treated early the possibility of safely discontinue treatment“. Ezequiel Ruiz-Mateos clarifies that the current criteria is to start treatment as soon as the patient is diagnosed, “for many reasons at the immunological and clinical level.” Hence the interest in having “biomarkers or factors that indicate in whom can be suspended therapy without the risk of the virus rebounding, allowing them to be off treatment for years and, in some cases, perhaps even becoming long-term controllers of the virus.”
On the other hand, this work also shows traits at the immunological level that could potentially help reproduce the ability to control the virus in other individuals with the infection.
Treatment ‘matures’ the immune system
Another finding of the study that this scientist highlights is that “the treatment modifies the ability of the immune system to control the virus. Even if patients have not started therapy immediately, perhaps when they have been treated for a long time, due to the characteristics of their immune system, they achieve that ability to corner the virus in regions of the genome where it is more difficult to replicate. Perhaps we will now find more controllers among the treated patients; there may be more people cured than we think,” she predicts.
With this premise, Ezequiel Ruiz-Mateos works at IBiS in a line of research on controllers. A few years ago, along with other Spanish researchers, he reported the case of another type of infection controller, the so-called elite, patients who manage to keep the virus at undetectable levels without ever taking antiretrovirals. Specifically, in that work carried out by several Spanish centers, and published in Scientific Reportsa follow-up was carried out on three patients (one man and two women) who contracted the infection between 1988 and 1992, but who had the virus under control despite never having received treatment.
Along with the controllers (aftertreatment and elite), anecdotal cases of HIV cure Worldwide. These are patients with the infection who, due to a hematological disease, such as leukemia, upon receiving a transplant of hematopoietic progenitors (bone marrow) with a certain genetic mutation, incorporate the ability to reject the virus.
However, despite the interest that this handful of cure cases may arouse, the reality is that now they can contribute little to the majority of patients with HIV, since they are based on a treatment that is not exempt from significant risks and that is acceptable for everyone. all people with HIV. Instead, Ezequiel Ruiz-Mateos points out, “identifying the traits of post-treatment and elite controllers can provide extrapolated data that could help many patients.”
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