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Why and when does HIV rebound after ‘remission' ?

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Scientists have found a way of predicting the clinical progression of HIV in infected individuals by measuring the levels of HIV-1 (Human Immunodeficiency Virus Type 1) DNA in white blood cells. The technique might be used to calculate how long it takes for the virus to return once treatment has been suspended.

Results are published in the journal eLife by Dr John Frater and colleagues at the University of Oxford (UK), University College London (UK), Imperial College London (UK), and The Kirby Institute of New South Wales (Australia).

HIV is currently an incurable, chronic infection that is manageable on antiretroviral treatment (ART). However, once a patient stops receiving this treatment the virus almost always returns. At present, the standard way of measuring the progression of the disease within a patient is by measuring the amount of HIV within a small sample of blood, a measure known as the viral load. High viral loads are predictive of a more rapid disease progression.

The next step in advancing our ability to potentially cure HIV is to find a way to predict how long it will take for the virus to rebound in patients on ART treatment when therapy is interrupted. In their paper, the team suggests that by measuring HIV-1 DNA -- some of which has been integrated into the genetic material inside patients’ cells -- it is possible to gain a clearer picture of this timeline.

To find the link between HIV-1 DNA levels and clinical progression of the disease, the group measured HIV-1 DNA levels in the white blood cells (CD4 T cells) of 154 HIV-positive individuals before anti-HIV therapy, at the point of stopping therapy, and at regular time intervals after therapy. They then compared these levels with known markers of clinical progression.

They found that the level of HIV-1 DNA within a patient’s white blood cells corresponded directly with the time taken for persistent, detectable levels of HIV in the blood to return, having been undetectable as a result of the therapy. The researchers hope to be able to use this finding to predict how long it will take the virus to rebound once a patient has stopped antiretroviral medication.

“Many researchers are striving to find a cure for HIV infection. Although still a distant goal, our data suggest that some people might be more curable than others, and that it might be possible to design a series of tests to use in the clinic to help identify them,” said John Frater, MRC Senior Clinical Fellow at Oxford University and co-senior author. “In this way we might be able to advise as to who should stay on their current treatment and who might be a candidate for either a trial of stopping therapy or even a new treatment in the future.”

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