The proliferation of the virus persists even when RNA is undetectable ...
Studying the challenges of previous beliefs about HIV remain asleep and the graphics a "path to a cure"
CHICAGO - A team of international scientists led by Northwestern University found that HIV is still replicating in lymphatic tissue, even when it is undetectable in the blood of patients on antiretroviral drugs.
The results provide a new critical perspective on how HIV persists in the body despite potent antiretroviral therapy (ART).
A WAY TO HEALING
"We now have a path to a cure," said the corresponding authorDr. Steven Wolinskychief of infectious diseases in theNorthwestern University Feinberg School of Medicineand a doctor of the Northwestern Medicine."The challenge is to deliver drugs in clinically effective concentrations where the virus continues to replicate within the patient."
The article on new ways to cure HIV was published in 27 in January in the journal Nature.
Combinations of potent antiretroviral drugs rapidly suppress HIV to undetectable levels in the bloodstream of most patients, but HIV persists in a viral reservoir within the lymphoid tissue in the body. The virus quickly rebounds in the blood if patients stop their medications. This suggests that latently infected cells and / or low levels of HIV replication in progress maintain these viral reservoirs.
So far, most scientists believed that the reservoir only contained long-lived infected cells in resting state rather than newly invented cells for various reasons. First, no one had seen viruses with the new genetic mutations that inevitably arise when HIV concludes growth cycles. Second, most patients do not develop resistance mutations to medications that may appear likely if HIV is raised in the presence of drugs.
Low level replication of HIV in lymphoid tissue
The team examined viral sequences in serial samples of lymph node and blood cells from three HIV-infected patients at the University of Minnesota who had no detectable virus in their blood. Scientists found that the viral reservoir was, in fact, constantly replenished by replication of low-level virus in lymphoid tissue with infected cells, passing from these protected sanctuaries to the blood.
Because infected cells in drug sanctuaries within the lymphatic tissue can still produce new viruses, infect new target cells and replenish the viral reservoir, it was not possible to purge the entire body of latently infected cells and eradicate the virus.
A mathematical model traced the amount of virus and the number of infected cells as they grew and evolved in the drug sanctuaries, then moved through the body. The model explains how HIV drug can grow in sanctuaries in lymphoid tissue where the concentrations of antiretroviral drugs are lower than in blood and that viruses with mutations that create resistance to high level drug does not necessarily emerge.
The results provide a new perspective on how HIV persists in the body despite potent antiretroviral therapy. The study also explains why the development of drug resistance is not inevitable when virus growth occurs in a place where drug concentrations are very low.
Provision of high concentrations of antiretrovirals
More importantly, this new understanding highlights the importance of delivering high concentrations of antiretroviral drugs in all parts of the body where HIV can grow. Drugs that enter the newly discovered sanctuaries will be a prerequisite for the elimination of the viral reservoir and ultimately a step toward a cure.
"The study is exciting because it really changes the way we think about what is happening in the treated patients," said co-author Angela McLean, mathematical biology professor at the University of Oxford, who supervised the mathematical modeling. "This helps explain why some strategies that tried to clean the reservoir failed."
Other authors of the paper include Ramon Lorenzo-Redondo, Eun-Young Kim and Sudhir Penugonda of Northwestern University; Helen R. Fryer of the University of Oxford, Oxford, UK; Jeffrey Chipman, Timothy W. Schacker and Ashley T. Haase of U of M, Minneapolis; Trevor Bedford of Fred Hutchinson Cancer Research Center, Seattle; Sergei L. Kosakovsky Pond of Temple University, Philadelphia; Yoon-Seok Chung of the National Institutes of Health of Korea, Korea; Courtney V. Fletcher of the University of Nebraska Medical Center, Omaha; Michael H. Malim of King's College London; Andrew Rambaut of the University of Edinburgh, Edinburgh, UK; and John Archer of the Center for Research on Biodiversity and Genetic Resources University of Porto in Portugal.
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Editor's note: After my wife reviewed the article she came up to me with a simple question:
"Cau! How and why do these drugs deepen in the cells? "
I told her the obvious:
-"I do not know!"
And I do not know. But it occurred to me and I commented with it what I share with you:
This reservoir, Mara, do you know what I think?
I look at it and see that it is such a complex, so _timidated_ thing that seems almost to be *** well planned? ... ***
Send to your friends [dqr_code post_id = "133562"]
The study was supported in part by DA033773 grants AI1074340 and GM110749 the National Institutes of Health, grant G1000196 by the Medical Research Council, grants 278433-PREDEMICS the Framework Program for Research and Technological Development, grants 260864 by the European Research Council, Oxford Martin School, All Souls College and the Royal Society.