Study reveals how some HIV patients curb infections after stopping antivirals

People who contract the AIDS virus (HIV) must be on lifelong treatment with antiretroviral drugs to keep the infection at bay and avoid transmitting it to others.. However, in some patients the virus does not reappear when treatment is stopped.. These minority cases are known among researchers in the field as post-treatment controllers, and their study is essential to find clues that can, in the future, advance curative treatments for the infection..

Post-treatment controllers are patients who start antiretroviral therapy very early and whose immune system is able to control the infection on its own when treatment is stopped. 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.

More information on the immune characteristics of these types of patients is published today in Science Translational Medicine. 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.

The scientists have compared six post-treatment controllers and six other patients who discontinued therapy without managing 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) of the Virgen del Rocío University Hospital, Ezequiel Ruiz-Mateos Carmona, points out that, “normally, autologous neutralizing antibodies fade quickly and fail to control the virus, but in this study they observe that With treatment, 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 associated with the fact that viral sequences are more homogeneous, from which it can be inferred that the presence of autologous neutralizing antibodies with greater viral inhibition capacity is associated with greater containment of the pathogen and, therefore, with less replication capacity and diversity”.

These combined traits may constitute “a biomarker that indicates in early treated patients the possibility of safely discontinuing treatment”. Ezequiel Ruiz-Mateos clarifies that the current criterion 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 therapy can be suspended without the risk of the virus rebounding, which would allow them to be without treatment for years and, in some cases, perhaps even become a controller.” long-term of the virus”.
On the other hand, this work also shows features at the immunological level that would 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 this ability to corner the virus in regions of the genome where it is more difficult for it to replicate.. Perhaps we will now find more controllers among the treated patients; there may be more people cured than we think,” predicts.

With this premise, Ezequiel Ruiz-Mateos works at the IBiS in a line of research on controllers. A few years ago, together 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 having taken antiretrovirals.. Specifically, in that work carried out by several Spanish centers, and published in Scientific Reports, 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 not having have never received treatment.

Alongside controllers (aftercare and elite), anecdotal cases of HIV cures have also been reported around the world.. 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 cases of cure 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 all people with HIV. On the other hand, Ezequiel Ruiz-Mateos points out, “identifying the traits of post-treatment and elite controllers can provide extrapolated data that could help many patients.”