Combining immunotherapy and antiretrovirals could help eliminate HIV

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They show that people who have just been diagnosed with HIV infection who start immunotherapy at the same time as antiretroviral treatment clear the virus better and their immune response is enhanced.

There is currently no cure for HIV (human immunodeficiency virus) infection, but thanks to antiretroviral therapy, those affected can lead a normal life even if they have to continue treatment for life to prevent the virus from reactivating. Now a clinical trial has shown that administering immunotherapy together with antiretroviral treatment at the beginning of said treatment would help eliminate the virus and stimulate the immune response that is responsible for suppressing infected cells and reducing the HIV reservoir.

The study, specifically, proposes a possible strategy to control HIV and prevent its persistence without the need for treatment, which consists of administering an antibody called 3BNC117 right at the start of antiretroviral treatment, and not later on, as previously believed. Research has shown that patients with viruses sensitive to the antibody used can control the virus better and longer in the absence of treatment compared to those who have not received immunotherapy or those who had viruses resistant to treatment.

The clinical trial has been led by the Aarhus University Hospital (Denmark) and has had the participation of the IrsiCaixa AIDS Research Institute – promoted by the “la Caixa” Foundation and the Department of Health of the Generalitat de Catalunya. The results show that administering immunotherapy based on this antibody helps eliminate HIV in the blood and improves the immune response that eliminates infected cells. People included in the study with viruses sensitive to the antibody used were able to control HIV for a longer time throughout the 12 weeks in which treatment was interrupted.

“These new results tell us, for the first time, that performing the intervention just when treatment is started would limit the persistence of HIV”

In the studies of immunotherapy with antibodies that have been carried out so far, people who have been receiving antiretroviral treatment for a long time have always participated. “These new results tell us, for the first time, that carrying out the intervention just when treatment begins would limit the persistence of HIV and this opens a new door for all of us who are dedicated to researching the eradication of this virus,” he said. explained Javier Martínez-Picado, ICREA researcher at IrsiCaixa and co-author of the article, which has been published in Nature Medicine.

Lower viral load and increased ability to clear HIV

The researchers conducted a phase 1b/2a clinical trial with 55 people who had just been diagnosed with HIV and were starting antiretroviral therapy; 15 of them were given this treatment alone, and the rest received the antiretroviral regimen together with the 3BNC117 antibody, alone or in combination with romidepsin – a drug that has not shown a significant effect in this situation – for one year.

The results showed that HIV was cleared from the blood more quickly in the group of patients who had received antiretroviral treatment and the 3BNC117 antibody, compared to those who received only treatment without immunotherapy. In addition, in people with viruses sensitive to the antibody, the number of infected cells with the ability to produce new viruses is reduced. “Thanks to a technique designed and patented by IrsiCaixa called VIP-SPOT, we can detect and quantify these cells which, in fact, are possibly responsible for the viral rebound suffered by patients when they abandon treatment”, pointed out María Carmen Puertas, researcher of IrsiCaixa and co-author of the article.

This could be explained in part by an increase in protective cells directed specifically against HIV, a key response of the immune system to control the infection. To test whether immunotherapy had any effect on virus control when antiretroviral therapy was not administered, 20 participants discontinued treatment one year after starting it.

The results of the trial have revealed that practically all individuals (5 out of 6) with virus sensitive to the antibody and who had received antiretroviral treatment and immunotherapy remain, for 12 weeks, with controlled levels of viral load. In contrast, people who had received antiretroviral treatment without immunotherapy, or had virus resistant to the antibody, needed to restart treatment sooner.

The goal of scientists doing research on HIV infection is to find a way to control the virus without requiring the patient to take lifelong treatment. “Results such as those obtained in this study show us possible ways to achieve this goal, that is, functional healing. Despite the good news, further research is needed to design strategies that demonstrate their effectiveness in the entire population living with HIV”, concludes Martínez-Picado.

Sources: IrsiCaixa and “la Caixa” Foundation

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