Vaccines, cell therapy, and definitive solutions: what does the future hold for HIV treatment?

By Fernanda Bassette, from the Einstein Agency - In the 1990s, receiving a diagnosis of HIV infection (the virus that causes AIDS) was like a "death sentence." There were no treatments available, and this was the natural progression of the disease. But as soon as the first medications against HIV appeared, the scenario began to change, and Brazil became a pioneer and a world reference in public policies for treating the disease.

According to David Lewi, an infectious disease specialist at the Albert Einstein Israelite Hospital, HIV treatment has evolved significantly since the arrival of the first medication, the famous AZT, which is currently obsolete. “AZT had a very successful history in combating the disease, but over the years, drugs have improved in terms of safety and toxicity, side effects have decreased, and nowadays most patients take only one pill a day. Abroad, there are already cases of patients taking monthly injections,” explains the doctor, who is also a retired professor from the Federal University of São Paulo (Unifesp).

Currently, antiretroviral therapy aims to make the viral load undetectable—which doesn't eliminate HIV, but interrupts the transmission of the virus. For the treatment to be truly effective, continuous and uninterrupted use of the medication is necessary; otherwise, the latent virus will circulate again.

This happens because existing medications only work on viruses circulating in the blood – they cannot reach those that are in a latent state inside cells. “When the virus is dormant in the cells, without activation, it is not causing damage to the immune system and the medication cannot reach them. If the patient stops taking the medication, eventually these viruses that are 'hibernating' will start circulating again,” the doctor explains.

A cure in the future?

Since poor adherence to medication is one of the biggest challenges in the fight against HIV, researchers have been searching for a treatment that is for a limited time, rather than for life, over the last decade. “Instead of taking the medication indefinitely, the goal is to expel the latent virus from its 'sanctuary' and, once it enters the bloodstream, eliminate it through the medication. Then, in the future, we could stop the medication and the patient would be effectively cured,” explains Lewi.

Another attempted cure is the complete elimination of the virus – as occurred in the case of the so-called "Berlin patient." Timothy Ray Brown, considered one of the very few people cured of HIV infection, was diagnosed with acute myeloid leukemia and, in 2007, received a bone marrow transplant from a donor with a genetic mutation that would guarantee resistance against the virus.

“The doctors chose a compatible bone marrow donor who had the genetic deletion that prevented the HIV virus from entering the cells. And it worked. Since then, there have been a few more cases like this in the world, but nobody is thinking of establishing this as clinical practice because, in addition to being an expensive procedure, bone marrow transplantation itself carries a risk of mortality,” he says.

The use of cell therapy against the disease is also being studied. In research conducted by Unifesp, in conjunction with the Istituto Superiore di Sanità in Rome (Italy), scientists performed genetic sequencing of the virus circulating in the cells of each patient. These cells were then processed and reinfused, as in an autologous bone marrow transplant (where the patient's own cells are collected and used later). Two of the study participants had undetectable viral RNA in the experimental protocol, showing a possible path for personalized cell therapy against HIV, taking into account both the patient's immune system and the individual's viral profile. The results were published in [publication name missing]. scientific magazine AIDS Research and Therapy.

HIV vaccine

Developing an HIV vaccine is another endeavor for researchers. “HIV is a virus that undergoes numerous mutations, and to date, no center has managed to create an antibody through a vaccine that could eliminate it. HIV creates loopholes against these antibodies. Unfortunately, all vaccines attempted so far have not induced sufficient immunity against HIV,” explains Lewi.

According to the infectious disease specialist, several centers worldwide are searching for a cure for HIV, but, for him, the most promising development is that of a definitive treatment. “What I want to highlight today is the ease with which patients take the medication, with increasingly simple regimens and very few side effects. At this very moment, it is still fundamental that the patient adheres to the treatment. But I foresee that, in the future, perhaps in about five years, we can talk about a definitive treatment, for a pre-determined time, until the patient can stop taking the medication and consider themselves cured,” he concluded.

AIDS in Brazil 

Even though the number of new cases is falling in Brazil, it remains very high. The most recent data from epidemiological bulletin from the Ministry of Health Studies indicate that in the last five years, the annual average of cases is around 36,8 new diagnoses and is increasing among young men. Worldwide, there are approximately 1,5 million new cases per year.

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