The side effects of antiretroviral therapy (ART) for HIV can be quite annoying, especially considering that it is a therapy that lasts for life: among these can occur the elevation of cholesterol and triglycerides, liver damage, redistribution of fats (lipodystrophy).
A study by immunologists from the US National Institutes of Health, published in Nature Medicine, shows what happens when antiretroviral therapy is stopped – under close medical supervision, of course. In particular, highlighting two cellular mechanisms that allow the immune system of HIV patients to keep the virus under control for long periods after the interruption of therapy.
The study will help develop pharmaceutical solutions to allow the remission of the virus even when antiretroviral therapy is suspended, so as to alleviate the problems caused by side effects.
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The study followed two HIV patients who started ART therapy immediately after contracting the virus, and continued with therapy for over six years. After discontinuing, under medical supervision, the patients were followed one for four and the other for five years, with regular check-ups every two weeks.
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The first patient was seen to be able to suppress the virus, with intermittent relapses, for about three and a half years. In the patient, the researchers found a high level of CD8 + T cells that specialize in destroying HIV-infected cells. The second patient, who instead suppressed the virus for almost four years before being reinfected by a different HIV strain, instead showed a weaker response of CD8 + T lymphocytes, but a very strong response of neutralizing antibodies over the whole period. time from discontinuation of therapy until viral “rebound” four years later. And it is believed that it was this powerful antibody response that nearly eradicated the virus.
We interviewed Tae-Wook Chun, head of the immunovirology section of the American Niaid (National Institute of Allergy and Infectious Diseases), co-author of the study together with Anthony Fauci.
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Professor Chun, how did the two patients you considered in the study manage to control the virus for such a long time?
“There are many factors that may have contributed to virologic suppression in our study participants in the absence of ART therapy. For the first patient, we believe that anti-HIV CD8 + T cells played an important role. For the second patient, however, there has been a crucial role for autologous neutralizing antibodies against HIV “.
What are the main differences between immunological defense based on neutralizing antibodies and that based on CD8 + T cells?
“Neutralizing antibodies mainly suppress HIV by binding to the virus and thus preventing re-infection. CD8 + T cells, on the other hand, suppress HIV mainly by destroying infected CD4 + T cells.”
What caused the virus to return in these two patients?
“When antiretroviral therapy is stopped, a variety of HIV-infected CD4 + T cells (often referred to as HIV reservoirs) can allow HIV to replicate. For one of the patients, however, a new infection was key.”
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Does your study give us any new direction to investigate to improve current HIV treatment?
“In the study we demonstrated that neutralizing antibodies in HIV-infected individuals who initiated ART therapy during the acute / early phase of infection could play an important role in virological suppression after discontinuation of ART therapy. Neutralizing antibodies, in the light of studies like ours, could bring interesting news for these patients. Furthermore, our study has shown the importance of frequent antiretroviral tests in patients who are presumably off therapy, and the possibility of superinfection as a reason of a sudden virological rebound after prolonged periods of virological suppression “.
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