Paolo Rossi Castelli 1 July 2021 7 min read

New drug blocks the HIV virus in advance

Tests in the United States with a monoclonal antibody that ‘inhibits’ the protein used by the virus to enter cells. The results appeared in the journal Nature Communications.

New hope of blocking the HIV virus, responsible for AIDS, as a preventive measure comes from tests on macaques carried out by Oregon Health & Science University (the HIV virus in non-human primates, like macaques, is very similar to the human one).

As the scientific journal Nature Communications reports, researchers have used a monoclonal antibody called leronlimab which managed to prevent the virus from ‘locking’ onto its target cells (T CD4 lymphocytes, fundamental elements in the immune system) and infecting them. Testing on humans will be started in the coming months.

Leronlimab is part of what is called pre-exposure prophylaxis (PrEP) in the United States, recommended for people who have sexual intercourse with people considered at risk.

Other drugs are also used for preventive purposes in both the United States and the European Union, not without some controversy, but their ‘main’ use is the treatment of people who have already contracted the disease. Leronlimab could open a new path, with significantly fewer side effects, compared to the others.

How does this monoclonal antibody work?

It is an antibody very similar to natural ones, but it was created using advanced genetic engineering techniques.

It should be remembered that the HIV virus needs a protein found on the surfaces of cells in the ‘host’ organism to infect them (as also happens with the SARS-CoV-2 virus, responsible for Covid 19). In HIV, the virus locks onto a protein called CCR5, found on the external wall of T CD4 lymphocytes.

Well, leronlimab blocks this protein, thus preventing the virus from linking to, and entering the cells of the organism.

A lucky circumstance

The protein CCR5 had been studied for some time because of its role as a ‘front door’ for the HIV virus.

Its importance was confirmed, in particular, when a patient, Timothy Ray Brown, was completely cured of HIV after receiving a bone-marrow transplant to treat a blood cancer.

Purely by chance, Brown had received bone-marrow from a donor with a rare genetic defect which prevented the expression (‘production’) of CCR5, and this had eliminated the infection. His case received worldwide attention inspiring many researchers and driving them to consider CCR5 as a possible target.

The researchers from Oregon Health & Science University used three groups of six macaques each, administering two different doses of monoclonal antibody or no treatment, for the study published in Nature Communications. All the animals were then exposed to contact with the primate’s HIV virus (similar, as we said above, to the human one). The macaques receiving the highest dose (50 mg per kilo of weight, every two weeks) showed total protection while two which received the lower dose (10 mg/kg) became infected, just like all those in the control group.

Tests on humans

The next step is tests on humans, probably with lower doses of antibodies because, in human beings, the CCR5 protein is expressed less compared to that in monkeys. In actual fact, testing on humans is ongoing even now, with positive results but on people who are already ill. In this case, the monoclonal antibody was administered with the classic antiretroviral treatment against HIV, showing effective.

Given the positive result, CytoDyn, the company which developed leronlimab, also sent the dossier to the American Food and Drug Administration (FDA, the agency that regulates the use of medicines in the United States) and it could ask for an extension to the indications for use for leronlimab, also on its own, in the near future.

The monoclonal was developed for easy self-administration at home, at longer intervals compared to the daily use of other treatments. However, it will be the FDA that, as always, gives it the green light.

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Paolo Rossi Castelli

Journalist since 1983, Paolo has been dealing with scientific divulgation for years, especially in the fields of medicine and biology. He is the creator of Sportello Cancro, the site created by corriere.it on oncology in collaboration with the Umberto Veronesi Foundation. He collaborated with the pages of the Science of Corriere della Sera for several years. He is the founder and director of PRC-Comunicare la scienza.