In a promising experiment in rhesus monkeys (translator's note - it is important to stress that the blood of these animals is very similar to ours and it was from studies of these monkeys was possible to create differentiating factors that made ultimately on the blood transfusion in a safe thing, based on the factor "RH +" and "RH", RH is that the Rhesus species name), Emory University scientists have used in Atlanta version adapted to the monkeyEntyvio Vedolizumab (), A drug used to treat intestinal inflammation, to produce persistent control of viral load and restoration of T cells in monkeys that were removed from the anti-retroviral therapy (ART).
The control and viral immune recovery persisted for weeks 30: 14 weeks after the monkeys were withdrawn from ART, but kept in similar Vedolizumab - Sending and for more 16 weeks after it is removed.
Translator's note, sought by Vedolizumab entry in wikipedia and found, I delved a little deeper and found a document in PDF whose link is this. From there I just brought relevant to understanding the text: Entyvio is a medicine that contains the active substance Vedolizumab. It is used in the treatment of adult patients with ulcerative colitis (a condition causing inflammation and ulcers in the intestinal lining) or Crohn's disease (a disease that causes inflammation of the digestive tract) in fact, the viral load control seemed to further improve the throughout the period when the monkeys were off all therapy.
Researchers are uncertain "About why the drug act"But seen an increase in a particular type of natural killer known (NK) cells that appear to be enabled by the drug in order to be able to treat HIV infection better and better immune response to the viral envelope protein of HIV that it resembles one of the answers in the study of trialthe RV144 HIV vaccine.
A small study in Vedolizumab human is already underway. [Editor's Note: This is rather a study that excites me, because it passes to humans. It is the observation phase of the action and any complications that the administration of a particular drug could have in a kind of organism infected with a virus or living on another condition]
Vedolizumab or α4β7mAbIt is a monoclonal antibody that binds to a cell surface molecule called α4β7. This molecule makes cells more susceptible to HIV infection and also binds to another protein in the lining of the small blood vessels that permeate the gastrointestinal tissues. One of the characteristics of the infection by HIV is the beginning of a massive and never completely restored destruction of immune cells in the gut: even the start of antiretroviral therapy can prevent this from happening. These immune damage can be a major mechanism ofimmune exhaustion progressive viewed in treating HIV infection.
The mechanism of drug action reduces intestinal inflammation in Crohn's disease and ulcerative colitis; It was licensed as a remedy for these conditions in 2013 in the US and Europe 2014. The hope is that we can do the same against HIV. Researchers raise hypothesis formulated α4β7mAb that can prevent HIV-infected cells reach the gut immune causing damage.
Experiments in monkeys have already shown that α4β7mAb had a promise as a drug to prevent HIV infection: In some animals that prevented infection while others were still infected but developed low viral loads.
In this experiment, reported in the journalScience, 18 rhesus were infected with SIV, the simian virus that causes AIDS, and therefore equivalent to HIV. Five weeks after infection, they all underwent ART. Four weeks later, in eleven patients were initiated a series of eight semes to three infusions per week α4β7mAb adapted to rhesus monkeys. Antiretroviral therapy was stopped after 13 weeks (18 weeks after infection). Infusions of α4β7mA b continued without ART until 32 weeks after infection (14 weeks without HAART). Then therapy was withdrawn from the "subject" of the experiment which continued until 50 weeks after infection (16 weeks of therapy at all).
The other eight monkeys with unspecific control protein infusions of immunoglobulin G (IgG), one of the proteins that provide the basic structure of antibodies but immunologically inactive.
Initially, all animals had after being infected with SIV (...) a high viral load SIV about one million copies / ml, but had their viral loads totally completely removed by the ART and after HAART be removed, viral loads quickly jumped to previous values in the eight monkeys study control.
In eleven monkeys that received the α4β7mAb three developed an anti α4β7mAb antibody response; in other words, their bodies rejected α4β7mAb and become resistant to their effects.
In the other eight, three monkeys suppressed CV (viral load below 50 copies / ml) for all 30 weeks without HAART. The other five were initially viral rebounds transient seen.
The average viral load in the eight monkeys 6300 copies / ml during the first four weeks after withdrawal of HAART between weeks 18 and 22 and ranged from undetectable and 200 copies / mL subsequently to 42ª week of the experiment. However in the last three samples taken at 44ª, and 46ª 50ª weeks, none of the eight monkeys had higher viral load 50 copies / ml (undetectable viral loads in this standard studies - it should be noted that in Brazil, the measurement of viral load could demonstrate 10 RNA copies because our tests are more accurate and not only "see viral load" if it is below 40. the DNA was not detected SIV (Simian Immunodeficiency Virus) intracellular in any animal in the period in which they were cut off from all processing.
Count cells CD4 in monkeys treated with α4β7mAb increased from a level of about 500 cells / mm3 almost 2000 cells / mm3 (!!!), which was the level before infection inoculated. There was a particularly strong and relative increase in types of T cells called "memory cells".
A PET scan of the monkeys showed that something unexpected happened.
It had been assumed that, as in the treatment of Crohn's disease, α4β7mAb would stop the traffic T cells to the intestine. And, instead, what was seen it was a T cell repopulation general uninfected essentially across the immune tissue including gut. The researchers made the observation that "did not know" if the viral load was being controlled by a more effective response of T cells, or the viral load controlled T cell allowed the repopulation of the gut by T cells (Editor's note: Looking so for his own abdomen, it does not seem noticeable improvement; it until you find out that all unfolded and extended intestinal tissue covers about one hectare and this, swapping kids, is the area of an official football field (...))
However there α4β7mAb suggestions that might have produced an interesting range of immunologic abnormalities protecting intestinal T cells of other infections. These changes included an increased a particular type of natural killer (NK) cells called cells secreting cytokines (Cytokineis an employee generic term to denote a large group of molecules involved in transmission of signals between the cells for the initiation of immune responses): these also express α4β7e this may have been enhanced to produce a more effective immune response by having the lock by α4β7. The protection of certain cytokines (circulating immune cytokine chemical mediation) rose, including retinoic acid, and interleukin-10, while an entire pane of inflammatory cytokines including D-dimer, interleukin 1β, a protein induced by γ Interferon and two chemicals associated with "intestinal leaks" all decreased.
immune reactivity tests showed that animals treated all had immune responses to a part of the surface of the HIV protein called loop V2 considering that only three of the control animals did too, but they were weak answers. Interestingly, a similar specific immune response was seen as a protective response seen in the study of RV144 HIV vaccine.
Implications and reactions
The researchers say they are still puzzled by immune responses seen and its effect on the achievement of new experiences. However, a small study of human Vedolizumab in 20 people have started at the National Institutes of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland.
Importantly, the results of immune modulating drugs in monkeys have not always been replicated successfully in humans. The monkeys were treated in early infection, whereas the human study is happening in chronically infected people who can present more of a challenge. The immune response anti-HIV views was impressive, but not as particularly strong. And there is the problem that three of the monkeys mounted an immune response to the very similar Vedolizumab, making it ineffective.
this alsonota complete cure: the blipes viral load seen outside of HAART suggest that α4β7mAb was suppressing SIV, but did not necessarily released the fully monkeys, and how long the effect would last beyond 16 weeks during therapy is still unknown.
However, this is a surprising result. In an official comment, theScienceIt states that the reactions of other scientists have ranged from "Fascinating" to "a first step complete" or "too incredible to be real."
NIAID Director Anthony S. Fauci said that "the results affected us" and they were impressive. "
Researchers cure HIV were all intrigued; Rafick-Paul Sekaly at Case Western University in Cleveland said: "That news will guide research in completely new direction." But Sharon Lewin of the University of Melbourne has issued the warning that "may be just a whim of the simian model."
In a separate article, the pioneer in research on HIV, Robert Gallo, speaks of the need for HIV healing approaches that lead to viral load down, instead of stimulating the body's response to HIV, calling them "calm and approaches snooze "instead of"Kicking and kill". he quotesthe trial of the Didehydro-cortistatin The inhibitor tatfor example.
The study with Vedolizumab might be an example of the same thing.
The verdict of Anthony S. Fauci?
"We'll find out soon enough if all this is a bunch of crap or really works."
Published: 14 October 2016
Translated from the original in aidsmap in Crohn's disease drug produces undetectability viral long-lasting and T-cell restoration off treatment in monkeys by Claudio Souza in 17 October 2016