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It Can Be Hard to Find the Healing of HIV, and the Healing of AIDS

Looking for the cure of AIDS is much like seeking the cure of Cancer: Quite difficult - Part 1 3


In recent years, a symposium specializing in the research of cura da AIDS Preceded the International AIDS Society (IAS) Conferences and this was no exception with a 1,5 Days Forum at the Curie Institute of Paris over the weekend of 9 IAS Conference on HIV Science (IAS 2017) Open.

Editor's note: And much good was said, revealed, discovered. And when reaching certain horizons, we find even broader horizons and that is how science, day after day, works in the search for an end to this pandemic ... Yes, yes, it is a pandemic and Brazil, who once was an example, today walks On the other hand, in spite of the fact that the state is secular, there is strong pressure from the religious group on the prevention policies that in Brazil are strictly null and void and I am developing a text where I narrate my horror when reading a story in one of these " , Where the person who writes about something she visibly has no idea what it is ...

This time there was a difference; This was called the IAS HIV Cure and Cancer Forum(Sodiety Internships for the Healing of AIDS and Forum for the search of the cure of the Cancer). This is due to the nascent recognition thatof AIDS and cancer cures have aspects in common, and that established or experimental cancer drugs may also play a role in curing HIV.

AIDS and Cancer: similarities and differences

cura da aids

There are many differences, of course, as Monsef Benkirane of the French Institute of Human Genetics said in an opening speech. HIV is caused by a viral infection and cancer due to spontaneous misbehavior by cells (although in some cancers this can be caused by infections). However, at the heart of the cell, this question is the same: cancer cells and HIV-infected cells have a genetic material that causes cells to grow uncontrollably (so cancer) or overturns the immune system. HIV). This means that both are difficult to cure: potentially, Only one cell infected with HIV ou A cancer cell Can lead to relapse.

It also means that the same tools that are now leading to dramatic improvement in cancer cure and remission rates, including sophisticated drugs that target specific markers for cancer cells, can be used to HIV cure.

Monsef Benkirane at the Forum for the Cure of HIV, the Cure of AIDS and the cure of Cancer, IAS 2017. Photo of Marcus Rose / IAS

HIV-infected cells and those with cancer in development share a deadly trick. Cells with their devious DNA can "To differentiate" When they are under attack, either by drugs or by the immune system. This means that they retreat (or regress) to an earlier stage of cell evolution where they are invisible to the immune system.

Benkirane said:

"When you treat, you actually create new cancer stem cells."

In HIV, something similar occurs: energized and enslaved immune cells, which actively "Burn", But a proportion returns to a quiescent state, ready to go into action again as soon as antiretroviral therapy (ART) pressure is relieved.NT:This is exactly why you should avoid losing doses. A doctor from the AIDS House told me that some patients, more specifically young people, are struggling to become undetectable. Then they disappear. What the unfortunate do not know, that this abandonment will surely lead to the loss of the Status of Undetectable, that as many people are as bad as they are intrinsihsible (I offer this text to those who think that being undetectable can be a license to fuck without a condom - "Viral blipes". On the other hand there are "experts" saying that the condom is only 97% efficient. I offer these two links:

  1. The Truth About Condoms

This is "HIV reservoir", And its identification and destruction (for a complete cure) or reduction / containment (for long-term remission) is the central barrier to be overcome if we are to find a cure.

The line of attack most sought after by AIDS cure researchers used HDACs (histone deacetylase), drugs that "pull" the sleeper genes in the reservoir cells back to wakefulness. The whole strategy was called "kick and kill," as it was hoped that reservoir cells, once reactivated and visible to the immune system, could be killed naturally by immune responses or purged by drugs based on antibodies that direct them.

Healing of AIDS

But repeated experiments with different HDACs have shown that while they certainly arouse the cells in the reservoir and turn them into productive short-lived viruses, they are unable to prevent new cells from being "seeded" with HIV and then returning to a quiescent state . The size of the reservoir cells therefore does not change significantly.

Immune Control Point Inhibitors

The drug targets we really need to work on are the cellular molecules that cause the cell to stop the immune work it is doing and revert back to its quiescent state. Both cancer cells and cells infected with the AIDS virus are particularly rich in these receptors called checkpoint immune. It is thought that its function is when the body is facing a hostile environment ranging from viral proliferation to chemical attack, or the sequestration of a proportion of the immune system, so that not everything is permanently damaged.

There are several molecules of different immune checkpoints. Cells already cited by some anticancer drugs include CTL-4 (4 protein associated with cytotoxic T lymphocytes), PD-1, where PD stands for "Scheduled Death" (one of the things the PD-1 can do is make cells Self-Destruction), TIGIT (T-cell immunoreceptor with Ig and ITIM domains) and JAK (Janus kinase). These are all inhibitory molecules, touching cells in the reservoir state, although some such as the TLR (toll-type receptor) family are excitatory and the TLR agonists (stimulators) continue to be investigated as Cell activators.

Agent in the cure of the cancerAs with HDACs, a number of CTL4, PD-1 and JAK inhibitors already exist as anticancer drugs. These include the ipilimumab CTL-4 antagonist (prescribed under the brand name Yervoy®for advanced melanoma), the 1 PD-nivolumab antagonists (Opdivo) And pembrolizumab (Keytruda) Which are used for advanced melanoma, small cell lung cancer and kidney and bladder cancer, and the JAK baricitinib inhibitors (Olumiant) And ruxolitinib (Jakafi), Which are used against rare bone marrow cancer called myelofibrosis and also against autoimmune diseases such as rheumatoid arthritis and psoriasis. Some of these drugs have shown life-prolonging effects on cancers that used to be rapidly terminal.

The Healing and Cancer Forum heard about various experiences using these agents in patients with cancer with HIV. Timothy Henrich of the University of California, San Francisco, an investigator who previously produced periods of no HIV detection outside ART in two patients who received bone marrow transplants , Gave data from three patients with lung cancer and HIV who received multiple doses of pembrolizumab.

In all three patients, T cell activation measures decreased and in one patient, who was in ART, the amount of intracellular DNA (a measure of how many cells in the "reservoir" are infected) fell transient. In a third patient, who was not in ART, both their general T-cell function decreased as well as their viral load in the blood plasma.

Brigitte Autran of the Pitié Salpêtrière Hospital in Paris gave data from 12 patients with non-small cell lung cancer who received nivolumab. They were a diverse group. One was a cisparo and the other was a transgender woman, the others were gay men. They had ages between 40 and 77 and had been diagnosed between 1980 and 2005. The counts of CD4 ranged between 60 and 700 cells / Mm3. Most had viral loads below 20 copies / ml, although in two cases they were detectably detectable, with 34 and 53 copies / ml.

In one patient, the one with the lowest CD4 count, there was a significant increase in T cells and an increase in the proportion of cells with HIV-specific immune response. In another, an increase in the specific HIV immune response was accompanied by a significant decrease in intracellular HIV DNA. However, he was the only one who showed signs of a shrinking HIV reservoir and other immunological effects on him and other patients seemed transient.

Christina Gavegnano of Emory University in Atlanta, Georgia, presented data from animal studies of baracitinib in newly infected monkeys and found that, compared to lamivudine treatment, there was a reduction of 700 times in the number of non-dividing latent CD4 T cells established on body. The drug could be used as an addition to ART that would slowly shrink the HIV reservoir until the point at which a discontinuation of treatment could be considered. A human ruxolitinib test in adult 60 (A5336) is underway.

The results with PD-1 and CTL-4 antagonists and JAK inhibitors have so far not been impressive, with only a minority of patients demonstrating strong or long-lasting responses, if any. Sharon Lewin of the University of Melbourne said that interpreting studies of PD-1 blockers in people with cancer is already difficult because cancers are heterogeneous and people with HIV who are suffering from cancer may not be representative of other HIV- Positive results.

"We need to do studies on HIV-positive patients without cancer," she said. "And we need to study combination therapies. But combinations of immune control point inhibitors, while proving more powerful results in some cancers, are very toxic for use with people who only have HIV. "

In some studies of patients with melanoma, approximately 50% of patients suffered serious or life-threatening side effects or even drug-related deaths.

Reservoir-cell signal found

One thing that would help efforts to cure HIV and the use of new types of drugs to eradicate HIV-infected cells would be if the cells in the reservoir could be identified more easily. The proportion of central-stem cells that are infected with HIV - the cells in the reservoir - ranges from one per thousand to one per million. So far, however, we have had no clear way of identifying them - and that means there is no way to target these cells alone and no other cells with drugs, which is the way to reduce toxicity.

Translated by Claudio Souza's originalWhy Curing HIV May Be Like Curing Cancer - and it may be difficult,

Written by Gus Cairns and Published: 03 August 2017.

Reviewed by Mara Macedo

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