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Virus in the basement

Team explains how HIV hides itself and why the scheduled interruption of treatment against Aids does not always work

MIGUEL BOYAYANLaboratory technician Janaína Maria Alves, from the team from Unifesp, purifies the HIV’s genetic material, to understand how the virus escapes from the medicines.MIGUEL BOYAYAN

In the last few years, the team led by Ricardo Diaz, from the Federal University of São Paulo (Unifesp), has followed up step by step the changes that are taking place in the HIV’s genetic material in a relatively short space of time (three months), when the victims of forms of the virus that are resistant to the medicines adopt the strategy of a scheduled interruption in the treatment – they stop taking the medicines for 12 weeks and then take up the therapy again. One of the members of the group, Wilson Pereira Silva, discovered the mechanism that allows the resistant virus to escape from the scheduled interruption, planned precisely to reduce the resistance to medicines.

Up until now, international research indicated that taking the medicines away could bring about alterations capable of reducing the population of resistant viruses, while the non-resistant ones, in evolutionary terms closer to the viruses found at the beginning of the infection, should have more favorable conditions for growth – next, the more viruses more sensitive to the medicines would be eliminated with the reintroduction of the medicines. The three-month interval also ought to be sufficient for the defense system to recycle the lymphocytes, the target cells for HIV, replacing the contaminated ones with the genetic material of the virus by other healthy ones. That what not was seen to happen.

In a study that is part of a thematic project coordinated by Ricardo Diaz, Wilson Silva found that the virus can remain alive for more time – in an inactive form – in populations of lymphocytes that are to be found in a sort of hibernation. The resumption of the treatment appears to arouse these dormant cells, which start to produce viruses that are resistant to the medicines. Analyzing a gene responsible for producing part of the HIV capsule, Diaz’s team confirmed that the viruses awakened with the removal of the medicines had accumulated fewer alterations and were therefore genetically closer to those that had started the infection.

Reduced resistance
In another study coordinated by Diaz, Domingos Matos dos Santos, from the Federal University of Pará (UFPA), assessed how 35 patients with HIV resistant to medicines responded to the scheduled interruption of the treatment. The strategy was effective – eliminating the resistance of the virus to medicine – in only 34% of the cases. For the other patients, the benefits were small or nonexistent. But the news also has some positive aspects.

In the light of these results, Santos decided to see what was special about these 12 people for whom the interruption had worked well. He saw that, in these cases, the quantity of virus in the blood was low, and the number of lymphocytes high, even before the beginning of the treatment – or, as the doctors say, the initial profile of the infection was good. “These results indicate that scheduled interruption should only be adopted when the initial picture of the disease is favorable”, says Santos. “It is a strategy that calls for an individualized assessment and for the doctor to know in detail how the infection has evolved in the patient.”