Saturday, April 1, 2023

How Close To Hiv Cure

‘i Am Not The Sort Of Person Who Gets Hiv’

HIV Cure Close: Breakthrough after virus vanishes in mans bloodstream

Just as young people see it as an older person’s illness, many see the virus as something affecting gay men only.

Worldwide, just over half of people with HIV are women – and it is the biggest killer of women of reproductive age, according to Christine Stegling, of charity Frontline Aids.

But few women she speaks to are aware of their risk.

“It’s a very important data point to engage with, because women who are in that age group and women who might want to become pregnant have to have difficult conversations about unprotected sex,” Ms Stegling says.

While huge progress has been made, the misinformation still circulating can leave people without jobs, relationships, the right treatment or even a diagnosis in the first place.

Everybody Is Racing To See If They Can Find A Cure

I end my conversation with Fauci by asking one more question. Every time we run a story about a potential cure for HIV, someone will inevitably make a comment on our Facebook along the lines of: That will never happen. Drug companies make too much money from keeping people on medication!

Given the history of gay men, HIV and pharmaceutical companies, such wariness is perhaps understandable.

Has Fauci himself experienced the frustration or impatience felt by many when it comes to finding a cure?

I can tell you that if a drug company found the cure for AIDS, they would be more rich than any other company that has any other drug, he says emphatically.

People are really trying to find a cure. Theyre not not going to find a cure because they want to keep selling their drugs everybody is racing to see if they can find a cure.

Unc Hiv Cure Center Awarded $262 Million Over The Next 5 Years

The National Institutes of Health will award $53 million annually to 10 research organizations over the next five years to continue working toward curative therapies for HIV. The Collaboratory of AIDS Researchers for Eradication , led at the UNC HIV Cure Center by David Margolis, MD, is one of two programs to have received funds for all three five-year grant cycles since 2011.

CHAPEL HILL, NC The National Institutes of Health has awarded approximately $53 million in annual funding over the next five years to 10 research organizations in a continued effort to find a cure for HIV. The new awards for the Martin Delaney Collaboratories for HIV Cure Research program, initiated in 2011, further expand the initiatives 2016 renewal from six institutions to 10, and represent a funding increase of approximately 75 percent. Additionally, one of the new grants is focused specifically on HIV cure research in infants and children.

The Collaboratory of AIDS Researchers for Eradication , which will receive $5.2 million for each of the next five years, was one of the two original collaboratory programs funded since the beginning, along with UC San Francisco. CARE is led by David Margolis, MD, professor of medicine at the UNC School of Medicine, director of the UNC HIV Cure Center.

Read more about the collaboratory and the organizations funded this round at the NIAID website.

UNC Contact: 919-923-0959

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Eliminating The Virus Completely

The other main approach to curing HIV is called viral eradication, which means ridding the body completely of the virus, including the proviral DNA in latently infected cells. This is also called a sterilizing cure, because it eliminates the infection, as well as a classic cure, that is, a cure in the truest sense of the word. The strategies being explored in this category have fanciful names like shock and kill and block and lock, among others.

Reversing latency, trashing the reservoir. In the shock-and-kill scenario, scientists are exploring strategies that use drugs to goose the latently infected cells of the HIV reservoir to express HIV proteins on their outer surface. Once those resting cells start producing viral proteins, they can be spotted by an enhanced immune systemor by drugsthat destroy the infected cell. Currently, several latency-reversing drugs are being evaluated in the laboratory and in human clinical trials.

Fortifying immune cells against HIV. Left untreated, HIV destroys the immune system of most PLWH, leading over time to opportunistic infections, HIV-related cancers, and death. A small fraction of PLWH, however, maintain viral suppression even without ART. Somehow, their immune systems are protected naturally from the virus and its ravages.

Viral Clearance Or Control

Researchers Hopeful New Treatment Leads To HIV Cure

If and when scientists are able to purge the viral reservoirs, the next step would be to either clear the viruses before they can reestablish reservoirs or control the viruses so that both latent HIV and circulating HIV are below levels where they can cause immune injury .

Antiretroviral therapy on its own will not likely accomplish that, given that it can’t stop the reestablishment of reservoirs. To this end, most scientists agree that multiple agents will be needed.

Among some of the approaches currently under investigation:

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Glaxosmithkline To Begin Human Trials For Hiv Cure

GSK is aiming to find a cure for HIV while also developing longer-acting drug treatments and preventive therapies.

GlaxoSmithKline, the British pharmaceutical company is planning to conduct human trials to find a cure for HIV, Money Control reported.

A Kaiser Family Foundation study recently found that in 2019, 38 million people globally were living with HIV. Thus, the trials by the pharmaceutical company would be a ground-breaking effort to find a cure to a common disease. The company would try to wake up a latent HIV virus within the participant’s immune system through therapies. Efforts would then be made to neutralise the virus once it’s activated in the body.

Dr Kimberly Smith, head of research and development at GSK’s HIV health division ViiV healthcare, said, “The idea is that you have to wake up the latent virus and try to get rid of it.”

The British Daily reported that a similar trial on non-human primates was successful in making the cells identify themselves.

While treatments have been discovered for HIV, there is yet a cure to be found, since treatments allow the patients to live a longer life with the virus. GSK already offers injection therapies as a treatment for HIV, where patients can just inject themselves once a month instead of taking pills every day. The company wants to make their injection therapies long-lasting, which would require their patients to inject themselves once every six months.

The Challenge Of Curing Hiv

Because of the nature of HIV, discovering a cure comes with some specific challenges. The most significant of these challenges is the viruss ability to hide itself and lay dormant in pockets of host cells that are unrecognised as harbouring HIV by the immune system. Even if an individual has successfully suppressed their HIV through ARV treatment, the hidden HIV, called the latent reservoir, can re-emerge if ARV treatment is stopped.

Because of this underlying barrier, examples of HIV cure have been few and far between throughout the entire history of the HIV epidemic. In fact, there have been only two instances of confirmed HIV cure, in which HIV cannot be found in in blood or biopsies of two PLHIV , and these patients went on to successfully stop daily ARV treatment and did not experience a rebound in their HIV. 1

These individuals were cured of their HIV after treatment for their separate cancer diagnosis, which required a series of difficult and intensive treatments. While their treatments were extremely high risk and not amenable to wide scale implementation, these instances of cure bring hope of what is possible in our efforts to end the HIV epidemic.

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Can The Cost Be Reduced

“Gene therapies are astonishingly expensive.”

As mentioned above, although genetic medicine shows enormous promise, the complexity and expense of its techniques means that at present it is unlikely to benefit most people who really need it.

Hans-Peter Kiem said that currently about 60 million people have conditions that could benefit from gene therapy. The vast majority of these either have HIV or haemoglobinopathies blood-malformation diseases such as sickle-cell anaemia and thalassaemia that are also concentrated in the lower-income world .

Dr Jennifer Adair, one of the first researchers to have proposed collaboration on gene therapies for HIV with African institutes, said that gene therapies have already been licensed for conditions such as thalassaemia, spinal muscular atrophy, T-cell lymphoma and a form of early-onset blindness.

But they are astonishingly expensive. The worlds most expensive drug tag goes, depending on which source you read, either to Zynteglo, a genetic medicine correcting malformed beta-haemoglobin and licensed in the US for thalassaemia, or Zolgensma, a drug licensed in Europe and given to children to correct the defective gene that results in spinal muscular atrophy.

Both cost about £1.8 million for a single dose. The price is not just due to the cost of the complex engineering used to make them, but because they are used to treat rare diseases and so have a small market.

Fifty Years Of Hiv: How Close Are We To A Cure

How Close Are We to HIV Cure?

Its half a century since the first known HIV-related death and two patients appear to have been cured of the virus. What does this mean for the 37 million still living with it?

Nobody knew what killed Robert Rayford. The African American boy was just 15 years old when he presented at St Louis city hospital in late 1968, but the medical team drew a blank.

Unexplained swelling in Rayfords genitalia soon spread throughout his body. Chlamydia bacteria, usually localised at the point of entry, coursed through his bloodstream. A small purple lesion on the inside of his thigh signalled cancer, but of a form usually found in elderly Ashkenazi Jews and Italians, not teenage black boys who had never left Missouri.

The teenager hardly spoke during the 18 months in which he received treatment at three separate hospitals. He was the typical 15-year-old who is not going to talk to adults, especially when Im white and hes black, one of his doctors would tell the St Louis Post-Dispatch almost two decades later. He told them he had sex with a girl from his neighbourhood, but gave little else away.

Tragically, pneumonia ended Rayfords young life during the night of 15 May 1969, but his body had been compromised some time before. Illnesses that a healthy body would ordinarily expunge met with no resistance. Rayfords clinicians, puzzled by his decline, persuaded his family to submit his body to an autopsy and preserved samples for inspection at a later date.

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All Attempts At Eradicating The Virus Have Not Been Successful

When asked about a cure, Fauci is understandably reluctant to raise anyones hopes again.

Weve got to be very careful. There have been so many attempts at a cure every single one of them, ultimately, rebounded, apart from a single patient the famous Berlin patient who had to do very, very expensive, Draconian manipulations, including stem cell transplantation, radiation and immune-suppression.

The so-called Berlin Patient is Timothy Brown, from Seattle, Washington. Doctors have been unable to detect the presence of HIV in his system after he underwent stem cell transplantation in 2007 to treat leukemia.

But that treatment, as pointed out by Fauci, has entailed other complications and has not been successfully repeated. In short, its simply easier to take anti-retroviral treatment.

All attempts at eradicating the virus have not been successful, says Fauci. There have been two approaches to a cure, and it really becomes a semantic issue of what you mean by a cure.

If what you mean by a cure is to truly eradicate the virus from the body, that is very difficult given the nature of the ability of the virus to integrate itself into the chromosomes of cells. Attempts to totally flush out the virus have been unsuccessful.

Fauci points out that NIAID has recently successfully observed this in animal studies. The monkeys studied showed no increase in viral load after 1-2 years of being off ART after successful treatment.

How A Functional Cure Might Work

One of the biggest challenges facing researchers is that HIV circulates in the blood and quickly embeds itself into cells and tissues throughout the body where it is shielded from detection by the immune system and can persist even in the face of complete viral suppression.

Since the virus is not actively replicatingbut is rather carried along passively as the host cell replicatesit is largely unaffected by antiretroviral drugs .

In order for a functional cure to be achieved, not one but multiple barriers have to be overcome to put the virus into remission. In recent years, scientists have dubbed this the “kick-kill” strategy, for which two primary aims need to be achieved.

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What Are The Challenges

While research on a cure is promising, there are some challenges. One is that we donât fully understand how HIV reservoirs work. Scientists are learning how to find, measure, and destroy them.

What about stem cell therapy? The CCR5 mutation that protects you from HIV is very rare, so itâs hard to find donor cells. Also, stem cell therapy is risky. People can reject donor cells and become very ill. Scientists are trying to find therapies that make a personâs own cells resistant to the virus, so they wonât need donor cells.

Another challenge is that males are the subjects of most HIV clinical trials, but about half of people with the virus are female. We need more studies to look at whether treatments will work on women and girls.

Even though research is very promising, it could be a few years before these treatments are tested to be sure they work well and are safe to use in many people who have HIV. âHIV Treatments: The Basics.â

National Institute of Allergy and Infectious Diseases: âHIV Cure.â

amfAR: âThe Countdown to a Cure for AIDS,â âPathways to an HIV Cure,â âMaking Sense of the Three Types of HIV Cure: The Berlin Patient, the Mississippi Child, and the VISCONTI Cohort.â

Fred Hutchinson Cancer Research Center: âWorld AIDS Day: Stepping up the search for a cure.â

Delaney Cell and Genome Engineering Initiative: âDefeat HIV: Scientific Overview.â

Evidence In Support Of A Functional Cure

Cure For HIV/AIDS 2019, Chinese Scientists are near to ...

While research into a functional cure has been on the table for some years, there were two events that provided the foundational proof of concept.

The first was Timothy Brown , who was the first of only a small handful of people “cured” of HIV. An HIV-positive American living in Berlin, Brown was given an experimental bone marrow transplant in 2009 to treat acute myeloid leukemia. Doctors selected a stem cell donor with two copies of a genetic mutation called the CCR5-delta-32, known to resist HIV in a rare population of elite controllers.

The resulting cure provided evidence that HIV could, in fact, be fully eradicated from the body. Even so, the procedure was too costly and dangerous to be considered a viable option.

A year later, in 2010, scientists were able to isolate two BnAbs called VRC01 and VRC02 from several elite controllers that were able to neutralize over 90% of HIV variants in lab studies.

The findings offered scientists hope that the same antibody defense that naturally occurs in elite controllerswho account for one of every 500 people with HIVmay one day be replicated in non-elite-controllers.

Insights from these and similar cases have provided scientists with the template by which functional cure research is largely based.

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Antibodies To The Rescue

Perhaps the most promising avenue of all in HIV research, McNamara says, is that of broadly neutralizing antibodies. These naturally occur in the immune systems of asmall fraction of HIV patients whose infection never progresses to AIDS. Researchers are studying how to harness them to treat other patients.

HIV is mutation-prone, which allows it to thwart the immune system and retroviral drugs that are made to target specific versions of the virus. For most patients with HIV, this means their immune system is always in hyperdrive, struggling to ward off a moving target. Its a nonstop war between the virus and the immune system, McNamara says.

But some patients have a special type of antibody that is continually effective. When it comes to broadly neutralizing antibodies, the virus is never able to win, McNamara says. The antibodies have it check-mated.

Though latent reservoirs are still an obstacle to them, broadly neutralizing antibodies show a lot of promise when it comes to keeping the virus at bay in particular, ensuring that the infection never progresses to AIDS and that its transmission risk is low. Some researchers are examining how they can be used both to treat and prevent HIV, while others are looking at how a combination of neutralizing and non-neutralizing antibodies may even have some effectiveness against latent cells.

Researching An Hiv Cure: The Main Approaches

  • ‘Activate and eradicate’ aims to flush the virus out of its reservoirs and then kill any cells it infects.
  • Gene editing changing immune cells so they cant be infected by HIV.
  • Immune modulation permanently changing the immune system to better fight HIV.
  • Stem cell transplants replacing a persons infected immune system with a donor immune system.
  • Although the stem cell approach has had some success in the past, its very dangerous for the patient. It would only be considered a viable option, if the person needed a stem cell transplant to treat another more deadly condition, such as very advanced leukaemia which, unlike HIV, doesnt have as many other safe and effective treatment options available.

    While there is promising research being carried out in these areas, there is no viable cure on the horizon.

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