What we know about HIV remission mechanisms – 01/27/2024 – Science

Last year, the news of a sixth case of HIV (human immunodeficiency virus) remission in the world brought hope to patients and doctors, but also raised doubts about the risks involved in the procedure.

This is because, as in the five previous cases, the remission of the virus that causes AIDS occurred after a bone marrow transplant to treat blood cancer. By receiving bone marrow from a donor, the patient was able to produce new immune cells free of the virus, confirmed more than a year after the remission was announced.

It is worth noting that remission is when there is no longer a focus of the virus in the body, while cure is when remission remains for five years after therapy.

But what happens to people with the virus who don’t have blood cancer? Are we still far from a cure for HIV?

According to Spanish virologist Asier Saez-Cirion, a researcher at the Pasteur Institute in France, it is important to highlight that there are several cases of patients with considered undetectable levels of HIV, and studies on these cases can help to get closer to the long-awaited cure.

“The cases of remission after transplantation are spectacular, but we also have remission in patients who go months without antiretroviral treatment and remain undetectable for years. There are hundreds of cases like this, and we are investigating their characteristics to better understand the remission of the virus” , he said, in an interview with Sheet at the end of November from his laboratory in Paris.

One of the lines of research underway at Pasteur is people who live for years with undetectable HIV without needing treatment. “We compared the three remission groups in a clinical trial: those who received a bone marrow transplant, individuals who naturally control the infection [por HIV] and finally people who manage to keep the virus undetectable years after stopping treatment. And we are still trying to understand the mechanisms behind natural infection control,” she said, adding that the study is still ongoing.

Patients who receive bone marrow transplants generally have an advantage because not only do they eliminate all infected cells from the body, they also prevent the infection of new cells if some copies of the virus are dormant in cells and cannot be eliminated.

This occurred in 5 of the 6 cases because the donors carried a mutation known as delta 32 of the CCR5 gene, which prevents HIV from entering cells. The CCR5 gene acts as an HIV receptor on the cell surface, but this variant prevents this binding, which is why it ends the infection.

The sixth case did not contain this mutation — in this case, it is likely that the transplant managed to eliminate all infected cells. Scientists now hope to be able to create gene therapy to modify genes in people without the need for transplants, which could expand access to treatment.

“We now know that people can live normally carrying this mutation, it is a good research lead to try an effective method of natural remission”, he explains.

In addition to cases involving gene therapy and bone marrow transplantation, Saez-Cirion recalls that there are other ways to reduce HIV viremia in the body, achieving a state in which the virus does not cause disease and cannot be passed on to others.

One of these is through early treatment with the antiretroviral cocktail. “We also know today that the sooner the patient starts antiviral treatment, in 5% to 6% of people they will be controlled for the rest of their lives. Controlling HIV means exactly that, not developing it, not transmitting it, basically, not having a signal of the virus. So now we are investigating what these individuals have in common, if there is something in them that could indicate a possible cure,” he said.

The ability to instruct the immune system, in particular cells known as NK (natural killers), to identify and attack HIV early may be behind this success. “In some of these individuals we found genetic traits associated with the formation of killer cells, and we are now developing a clinical trial to prove this association. If this is true, then it will be possible to think of targeted therapies to help the immune system of people who do not control the virus to fight it more effectively”, he states.

Another front of study is the use of CAR-T cells, which are immune system cells genetically modified outside the body and then reintroduced to attack the invader.

The researcher states that in the last 40 years, however, knowledge and treatment of HIV/AIDS have evolved a lot, mainly increasing patient survival. Gene therapies, immunotherapy, bone marrow transplants, antiretroviral drugs and even CAR-T are ways to combat the virus during or after the initial infection. There are also therapies that help prevent infection, such as PrEP (pre-exposure prophylaxis).

Anti-HIV vaccines are still a long way off, recalls the virologist, largely because of the complexity of the virus, since the same individual can carry dozens of different variants of the invader. As vaccines contain parts of the virus or the entire inactivated virus in their formulation, the different copies of the virus in the body would be able to escape protection. “There are some research groups investigating mRNA vaccines that induce protective neutralizing antibody responses, but they are very rare, and more complicated.”