Much remains to be done to find a cure for AIDS
Healing of HIV infection will involve combinations of various drugs and approaches, with only the treatment of HIV is not possible, the delegates heardTowards the Cure workshop held in advance ofAIDS2016 conferencein Durban.
The reason is the same, too: HIV can easily develop resistance to the individual agents, as sophisticated as broadly neutralizing antibodies and editing enzyme gene.
Dr. Anthony S. Fauci, head of the National Institute of Allergy and Infectious Diseases, told delegates that research for the cure of HIV is about the same HIV treatment phase as 1990; as with the first drug against HIV as AZT "zidovudine", it became clear that individuals or isolated strategies can have only a limited effect over and combinations of double therapies were starting to show a little more promising.
Most cutting-edge research for the cure is still undergoing laboratory blade-glass and / or in animal models of research model and human trials will inevitably have to be postponed for long.
Disappointment for an experimental combination
Even combinations that work they lack a crucial step in the sequence of events would have to happen for HIV-infected cells were purged from the Human Body. The workshop for healing and the main conference heard of disappointing results of a compound experimental design of three drugs;
drugs, immune modulatory vorinostat chosen because it can "wake up" long-term cell reservoir where HIV hides; hydroxychloroquine antimalarial drug, chosen to contain the effects of vorinostat as immune stimulant and prevent loss to HIV infection; and maraviroc entry inhibitor, chosen because it has the potential to stop the spread of HIV to new cells, since the cell reservoir is awake. This combination of 'WHV' was given to ten people living with HIV who had been diagnosed within two to four weeks of infection, immediately treated with antiretroviral therapy (ART) and maintained in HAART for at least two years.
It was hoped that the 'kick' given by this regime would induce the immune system of the body spontaneously eliminate the HIV-infected cells that had become visible to him, or naturally convert to a type of short-term virus would die. He hoped that the combination could extend the period in which people
could remain off HAART and / or impoverish the size of its viral reservoirs. However, if the viral load drop as fast in the "VHM recipients" receiving only as the ART and there was no change in the amount of HIV-infected cells in the reservoir.
The presenter Jintanat Ananworanich said at the workshop that the reason VHM not work was "probably" because, as other studies in the "kick and kill," found that it was not enough to "take the reservoir of cells infected with HIV out of hiding . It was revealed that natural immune processes of the body did not respond to these "called the killing" and that a "killer" component or a toxin that actively interfere with the newly awakened target cell reservoir would have to be added.
The study was also a reminder that the experimental healing regimens can not be totally harmless; the VHM combination affected kidneys and cause clotting problems blood and a participant had to stop because of kidney failure and low platelet count.
Two antibodies are better than one ...
Anthony S. Fauci spoke about his own laboratory work. He is focusing on the idea that with infusions called "antibodies widely
Neutralizing (bNAbs). These unusual antibodies have been discovered in the blood of some people chronically infected with HIV, where they have no effect against the virus because this has already developed resistance to them. But they have a potent suppressive effect against the virus in some individuals with short-term infection and can be used as injectable long-term drug, as both treatment and / or Prep. The hope is that a cocktail of bNAbs may eventually have enough suppressive power to allow people to remain off the conventional antiretroviral therapy for prolonged periods and the ultimate goal is for a vaccine or gene therapy that induces the body to make its own bNAbs.
Anthony S. Fauci showed study data of a called VRC bNAb01 that was given to HIV positive people three weeks before they stop antiretroviral therapy and then again at six-monthly intervals. People who had their antiretroviral therapy interrupted had viral load growth rose above 100 copies / ml or its CD4 count fell more than 30%.
The VRC01 was able to extend the time in which people could get out of antiretroviral therapy, on average, though not for long; compared with those on ART, given only an interruption of treatment, the viral rebound time averaged 30 days instead of eleven days. However as time to recover in one patient was only a week in two patients with viral rebound time it was four to five months respectively. (Note from the editor: These data make incongruous therapy and, in my jargon, would be like playing dice with my therapy, to "see what happens")
What makes the difference is the old big bugs of HIV treatment, resistance. Many people have taken pre-existing resistance to specific bNAbs and if this leads to VRC01 infusion of antibodies produced only 40% more viral control when compared to doing nothing. (The editor again: "rolling the dice").
There are, however, bNAbs newly discovered that are fifty to one hundred times more potent than VRC01. There are also "drug-accessory" that can be used to prolong the half-life of bNAbs blood - Add in a cancer drug called motavizumab, itself an antibody prolongs the half-life of bNAbs (the time for the blood levels of bNAbs fall 50%) five weeks to six months. (Editor's Note: Although the data - or roulette, for those who prefer)
However, ultimately, only bNAbs more infusions fail because HIV will develop resistance to them. bNAbs combination work better, would last longer and would be given in much smaller doses.
... And so are two pairs of "gene scissors"
Also in the healing workshop, another study showed that the principle that two drugs worked better than one that applies the technique of hi-tech edition of
gene also.Aidsmap reported in March (Editor's note: simply no time to we translate this article and it if it had been translated would "espinafrado" like so many others who encouraged us indeed)A technique in which literally "edited genetic information to cells infected by HIV. It involves infecting cells with RNA lengths composed of two components, a guide RNA derived from a natural CRISPR named compound, and endonuclease, a gene for a destructive enzyme cas9.
The guide RNA are able to drive the cas9 to the exact point where the external viral DNA is inserted so that the cutting and cas9 action of re-entry only removed the foreign DNA and did not cause collateral damage in genes nearby.
However,AIDSMAPs as reported later six SemansThe power of "gene" CRISPR / cas9 is short and it is vivid as HIV develops resistance to it very quickly - so quickly that it was feared this might have been "a worm-the-dead" with a "healing technique" .
However Monique Nijhuis at the University of Utrecht, which, in the Netherlands, showed in a healing workshop this fortunately was not the case. His team has developed eight different editors CRISPR gene / cas9 that target different parts of the genetic sequence of HIV. None of these worked well when used alone. However, when cells were infected with three specific pairs - the so-called editors genes MA3, IN5 and PR2 - and were then infected with HIV, a very low infection followed by complete viral suppression was the result, or if MA3 + PR2 no sign of infection, at least for the 55 days laboratory study lasted.
Here the gene probes were preventing HIV infection essentially arming cells with machinery HIV advocacy; Nijhuis commented that viral suppression, although so far not so deep, was seen where cells were infected with HIV first and then with the CRISPR / cas9s; They were then introduced as a treatment.
Gene therapy is a very early stage of development and, in the case of HIV, has not attempted even in animals: Nijhuis commented that many challenges remained, including the fact that they do not know why some pairs of probes gene worked better the other pair, and how to perform the task much more difficult to infect all cells completely from the body than simply infect all cells in a laboratory glass slide. It is also likely to be an expensive and difficult approach to adapt to low-income settings. However, it is encouraging that simply using two probes instead of one gene has restored power, which could be a way to remove the need incredibly HIV in the human body.
Published: July 20 2016
Translated by Claudio Souza Original in AidsmapentitledHIV will only be cured with combinations too, conference delegates hearreviewed by Mara Macedo21 in July 2016 AD
Ananworanich J.Effect of vorinostat, hydroxychloroquine and combination therapy on maraviroc viremia Following treatment interruption in Individuals initiating ART During acute HIV infection.Towards a Cure 2016 workshop, Durban, South Africa. Abstract OA3-5LB.
- This was Also presented the abstract at TUAX0101LB at the main aids216 conference - seehttp://programme.aids2016.org/Abstract/Abstract/10535
Fauci A.Addressing HIV Persistence: Challenges and Opportunities.Keynote address, Towards a Cure 2016 workshop, Durban, South Africa.
Nijhuis M.Combinatorial CRISPR / Cas9 approaches targeting different steps in the HIV life cycle can Prevent the selection of resistance.Towards a Cure 2016 workshop, Durban, South Africa. Abstract OA3-3. 2016.
- This was Also presented the abstract at WEPEA022 at the main AIDS conference 2016 - seehttp://programme.aids2016.org/Abstract/Abstract/4228