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.
How Is Hiv Treated
Basics
There are many treatments that can help people with HIV, and current treatments are very effective and safe. As a result, most people with HIV are living long and healthy lives. Treatment is recommended for everyone with HIV infection, and generally should be started as early as possible.
Medicines slow the growth of the virus or stop it from making copies of itself. Although these drugs don’t eliminate the virus from the body, they keep the amount of virus in the blood low. This protects the health of the person with HIV and also can prevent HIV from passing to sex partners.
The amount of virus in the blood is called the viral load, and it can be measured by a test.
There are several types of anti-HIV drugs. Each type attacks the virus in a specific way.
Pop question: True or false. HIV medicines eliminate virus from the body.
TrueFalse
Pop question: True or false. HIV medicines eliminate virus from the body.
Answer: FALSE. HIV drugs cannot eliminate HIV virus from the body, but they can reduce it to very, very low levels. The main goal of HIV drugs is to reduce viral load as much as possible for as long as possible.
Promising New Research May Soon Help Treat And One Day Cure The Chronic Disease
Just over a decade ago, researchers announced a first: They had cured a patient of HIV. Known as the Berlin patient, Timothy Ray Brown had needed a bone marrow transplant to treat his acute myeloid leukemia. Doctors used the opportunity to replace his bone marrow using stem cells from a donor with gene-based HIV immunity. It worked: Browns leukemia was cured, as was his HIV. More recently, in 2019, a second patient, this time being treated for Hodgkins lymphoma, was similarly cured in London.
But although these are the most famous stories where patients have been cured from HIV, their treatments represent just one option of many new approaches for tackling the virus and one of the least widely applicable. Its too invasive and too risky to conduct a bone marrow transplant on someone who doesnt already have cancer that requires the procedure especially considering most patients with an HIV diagnosis and access to care can effectively control the disease with drugs. In fact, a patient on antiretroviral therapy, or ART, today has the same life expectancy as a person without HIV.
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Could This Cure Mean The End Of The Hiv Epidemic
Unfortunately, there are societal and personal obstacles outside of the literal cure being scaled up and made available.
The HIV epidemic in North America continues to have worse outcomes across racial lines, and overlaps with a severe opioids epidemic in socio-economically worse off areas.
While Black people make up 13% of the US population, they are 43% of HIV-related deaths in 2018. These entwined factors create a difficulty of treatment for medical care is expensive, inaccessible and stigma continues to exist about having HIV in the first place.
Currently, the UK have made it possible for people living with HIV to access the COVID vaccine without declaring their medical status.
Dr Errol Fields, Johns Hopkins University School of Medicine, said: The racial disparities that so rapidly emerged with COVID-19 are a reminder that until these inequities are addressed, disparities in HIV and COVID-19 outcomes will persist and ending the HIV epidemic will remain elusive.
Across the world, HIV is a huge problem for women and girls who have to trade themselves sexually in exchange for access to resources like food, water and medicine.;
While many infectious diseases like HIV/AIDS do not have a direct link to the environment in their transmission patterns or vectors, disasters such as drought can still have a significant influence on the social conditions that shape and enhance vulnerabilities, said the researchers.
Reversing Hiv Latency And Destroying The Hiv Reservoir
Scientists are looking into strategies that induce latently infected cells to express HIV proteins on their outer surface so that an enhanced immune system or therapeutic agents can recognize these proteins and kill the infected cell. This strategy is sometimes called kick and kill or shock and kill meaning latent HIV is drawn out by latency-reversing agents, allowing the latently infected cells to be targeted for destruction by the immune system or other anti-HIV therapy. Currently, several latency-reversing agents are under investigation in the laboratory and in human clinical trials.
Once the latent HIV begins to replicate after the kick stage, components of the immune system or therapeutic agents kill the HIV-infected cells to ensure a complete eradication of the latent HIV reservoir. In 2015, a team of researchers at NIAID developed a double-headed protein called VRC07-CD3, which is a kind of bispecific T-cell engager, or BITE. One arm of this protein binds to a receptor on HIV-infected CD4 T-cells, prompting that cell to display HIV proteins on its outer membrane. In a separate step, the other arm of VRC07-CD3 then binds to these HIV membrane proteins while the original arm attaches to a killer T-cell in order to activate it and bring it in proximity to the infected cell. The activated killer T cell then kills the infected cell.;
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Hiv Hides In The Body
Scientists had hoped giving strong treatment medications so soon after birth would get rid of the virus or prevent it from spreading and doing damage.
The fact that the HIV virus eventually turned up in the âMississippi babyâ isn’t unexpected, says Robert Siliciano, MD, PhD, professor of medicine in the infectious diseases department at Johns Hopkins University School of Medicine. It supports the theory that HIV cells stay in the body, just out of view in a hidden “reservoir.”
“Curing HIV infection is going to require strategies to eliminate this reservoir,” he says.
How Does The Hiv Cure Work
The cure is not a drug that can be manufactured and administered like the COVID-19 vaccine.
Scientists have extracted stem cells from people who are resistant to HIV, then transplanting these cells into Mr Castillejo, who revealed his identity recently. The HIV-resistant cells then replace the non-resistant cells in the patient.
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What Is The Treatment
Stem-cell transplants appear to stop the virus being able to replicate inside the body by replacing the patient’s own immune cells with donor ones that resist HIV infection.
Adam Castillejo – the now 40-year-old “London Patient” who has – has no detectable active HIV infection in his blood, semen or tissues, his doctors say.
It is now a year after they first announced he was clear of the virus and he still remains free of HIV.
Lead researcher Prof Ravindra Kumar Gupta, from the University of Cambridge, told BBC News: “This represents HIV cure with almost certainty.
“We have now had two and a half years with anti-retroviral-free remission.
“Our findings show that the success of stem-cell transplantation as a cure for HIV, first reported nine years ago in the Berlin Patient, can be replicated.”
But it will not be a treatment for the millions of people around the world living with HIV.
The aggressive therapy was primarily used to treat the patients’ cancers, not their HIV.
And current HIV drugs remain very effective, meaning people with the virus can live long and healthy lives.
Prof Gupta said: “It is important to note that this curative treatment is high-risk and only used as a last resort for patients with HIV who also have life-threatening haematological malignancies.
“Therefore, this is not a treatment that would be offered widely to patients with HIV who are on successful anti-retroviral treatment.”
Is It Hard To Take These Drugs
The HIV medicines that currently are recommended are usually very simple and easy to take. Several drug combinations are available that package 3 separate medicines into only 1 pill, taken once a day, with minimal side effects.
For the great majority of people, HIV medicines are tolerable and effective, and let people with HIV live long and healthy lives. For some people, the drugs may be difficult to take every day, and for a small number, they cause serious side effects or don’t work well.
Once patients are on medications, they must work with their health care providers to find solutions for side effects and monitor how well the drugs are working.
The good news is that there are many excellent HIV medicines. Finding the right combination of medicines for each person is usually possible–a combination that controls the virus but does not cause side effects.
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Strategies To Cure Hiv
Whilst a person living with HIV can suppress the virus with antiretrovirals, there is no cure. A cure for HIV would be the total eradication of;the virus from the body. However, this is not the only option that scientists are looking into. Here are some of the strategies scientists are looking into for an HIV cure.;
Light Painting | JonathanCohen via Photopin
What Are The Types Of Hiv/aids Medicines
There are several different types of HIV/AIDS medicines. Some work by blocking or changing enzymes that HIV needs to make copies of itself. This prevents HIV from copying itself, which reduces the amount of HIV in the body. Several medicines do this:
- Nucleoside reverse transcriptase inhibitors block an enzyme called reverse transcriptase
- Non-nucleoside reverse transcriptase inhibitors bind to and later change reverse transcriptase
- Integrase inhibitors block an enzyme called integrase
- Protease inhibitors block an enzyme called protease
Some HIV/AIDS medicines interfere with HIV’s ability to infect CD4 immune system cells:
- Fusion inhibitors block HIV from entering the cells
- CCR5 antagonists and post-attachment inhibitors block different molecules on the CD4 cells. To infect a cell, HIV has to bind to two types of molecules on the cell’s surface. Blocking either of these molecules prevents HIV from entering the cells.
- Attachment inhibitors bind to a specific protein on the outer surface of HIV. This prevents HIV from entering the cell.
In some cases, people take more than one medicine:
- Pharmacokinetic enhancers boost the effectiveness of certain HIV/AIDS medicines. A pharmacokinetic enhancer slows the breakdown of the other medicine. This allows that medicine to stay in the body longer at a higher concentration.
- Multidrug combinations include a combination of two or more different HIV/AIDS medicines
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A Woman May Have Been Cured Of Hiv Without Medical Treatment
In dozens of other patients who suppress the virus without drugs, it seems to have been cornered in parts of the genome where it cannot reproduce, scientists reported.
A woman who was infected with H.I.V. in 1992 may be the first person cured of the virus without a risky bone-marrow transplant or even medications, researchers reported on Wednesday.
In an additional 63 people in their study who controlled the infection without drugs, H.I.V. apparently was sequestered in the body in such a way that it could not reproduce, the scientists also reported. The finding suggested that these people may have achieved a functional cure.
The research, , outlines a new mechanism by which the body may suppress H.I.V., visible only now because of advances in genetics. The study also offers hope that some small number of infected people who have taken antiretroviral therapy for many years may similarly be able to suppress the virus and stop taking the drugs, which can exact a toll on the body.
It does suggest that treatment itself can cure people, which goes against all the dogma, said Dr. Steve Deeks, an AIDS expert at the University of California, San Francisco, and an author of the new study.
Even among viruses, H.I.V. is particularly wily and difficult to eradicate. It inserts itself into the human genome and tricks the cells machinery into making copies. H.I.V. naturally prefers to lurk within genes, the most active targets of the cells copiers.
Shock And Kill Technique
HIV hides in reservoir cells in the body and can remain silent as long as a patient takes antiretroviral therapy. As soon as a patient stops taking ARTs, the reservoir virus wakes up and starts replicating all around the body again.Shock and Kill would wake up these reservoirs to activate the silent virus. Whilst counter-intuitive, the idea is to wake up every single virus and kill all the activated cells, destroying the reservoir in one go. If one virus survives then there is always a risk that it will be able to duplicate and the virus will return.Currently, scientists have identified drugs that will shock or wake up the silent reservoir cells. The next challenge is to identify a drug or method that can subsequently destroy these infected cells and avoid healthy cells. When destroying cells in the body, there is always a risk that drugs will target healthy cells, so this research moves carefully to avoid unnecessary damage.;Pharmacological reactivation of virus as a cure strategy ;;
Locks and Lockers | Eyad Elbayoumi via Photopin
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What Else Do I Need To Know About Taking Hiv/aids Medicines
It’s important to take your medicines every day, according to the instructions from your health care provider. If you miss doses or don’t follow a regular schedule, your treatment may not work, and the HIV virus may become resistant to the medicines.
HIV medicines can cause side effects. Most of these side effects are manageable, but a few can be serious. Tell your health care provider about any side effects that you are having. Don’t stop taking your medicine without first talking to your provider. He or she may give you tips on how to deal with the side effects. In some cases, your provider may decide to change your medicines.
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.
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We Should Applaud These Groundbreaking Discoveries But Were Not At The Finish Line Yet
This is why the Global Fund, the organization that receives 100% of money generated by partners, is so important. While the medical community continues to work on finding a safe, cost-effective cure for HIV/AIDS, Global Fund programs in over 100 countries are focused on scaling up access to daily antiretroviral medicationthe current, closest thing to a cure for people living with HIV. These programs also provide prevention services, care, treatment and education to the people most affected by HIV, which are crucial to limiting the spread of the virus.
Given the devastating impact of the current COVID-19 pandemic on the fight to end AIDS, supporting the Global Fund is more crucial now than ever before. Join and help ensure those living with HIV can continue to access essential programs and services.
After 40 Years Of Progress Its Time To End The Hiv Epidemic
Cross-posted from the HHS Blog
Despite the progress weve made over four decades, HIV persists as a serious public health challenge globally. Fortunately, ending the HIV epidemic is now within our reach.As we mark the 40th anniversary of the first official report about AIDS on June 5th, 1981, we pause to honor the more than 32 million people who have died from AIDS-related illnesses globally, including 700,000 people in the U.S.
Reflecting on those we have lost to HIV and AIDS, and standing alongside the HIV community, we recommit ourselves to ending the HIV epidemic, continuing the work that must be done, reengaging people with lived experience and a wide variety of stakeholders from all sectors of society, and to reenergizing our efforts to accelerate progress and ensure equity.
To move us forward towards this goal, on May 28, 2021, the White House published President Bidens Budget of the United States Government for Fiscal Year 2022, which includes a request for $670 million for continued implementation of the Ending the HIV Epidemic in the U.S. initiative .
Right now, 38 million people including 1.2 million here in the U.S. are living with HIV. While we still dont have a cure, we have made tremendous strides. Biomedical and scientific research advances have led to the development of HIV tests, many successful HIV treatments, prevention strategies, and improved care for persons with HIV.
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