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.
So Where Are We Now And Is It Worth It
If an effective HIV vaccine is that hard to create, will we ever get there? Thats a really tough question, said Jefferys. In science, there can always be surprises, good and bad. Its possible that Janssens will have protective power.
Hes referring to a vaccine from Janssen, a Johnson & Johnson subsidiary, that has recently been in a phase 3 trial among cisgender men who have sex with men and transgender people in Latin America, Europe, and the U.S., alongside a phase 2b trial among cisgender women at high risk for HIV in several African countriesand that was due to be analyzing results in July. Its not an mRNA vaccine, but a so-called vector vaccine, which uses a modified version of a different virus to deliver important info to human cells on fighting off HIV. The vaccine isnt able to induce broadly neutralizing antibody responses, but rather creates other kinds of immune responses that researchers think may have a chance of preventing HIV infection.
If the Janssen results are negative, Feinberg cautioned, that may be the last attempt to create a vaccine that sparks these types of immune responses. Future trials, he said, would only have the B-cell wing of the immune system left to concentrate on. But, cautioned Feinberg, “broadly neutralizing antibodies have to go through multiple steps of evolution to get to the structure that can bind to HIV,” meaning that creating such a vaccine will itself be a slow, multi-step process.
Tim Murphy
When Will An Hiv Vaccine Be Available
Scientists have swung from optimism to pessimism about the chances of developing an effective vaccine over the past thirty years. Scientists are becoming optimistic again after the results of recent studies.
Even if the large trials underway produce positive results after 2023, it will take several years for the results to be fully analysed and submitted for regulatory approval. Vaccine manufacturing will need to be scaled up and money will need to be pledged by donors to pay for HIV vaccination campaigns in lower-income countries. Also, further studies may be needed to check that vaccines effective in one clinical trial show similar efficacy in other populations.
Even if vaccine studies produce positive results in the next few years, this will not mean that the need for HIV vaccine research will stop. Further research will be needed to improve the efficacy of vaccines, to make vaccines easier and cheaper to manufacture, and to find out how to deliver them to the largest number of people in different regions of the world. Having an effective vaccine is one challenge, but another major challenge will be to make sure that everyone who is at risk of HIV can be vaccinated.
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Aids: Why Is A Cure So Difficult To Find
We look at the struggle to find a cure for AIDS that works
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The current strategy of HAART is to simultaneously administer several drugs to attack HIV at different stages of its life cycle. The most common drug regimes administer reverse transcriptase inhibitors to try to avoid the initial infection of cells in combination with drugs such as protease inhibitors which inhibit the production of new viruses in already infected cells. Some more recently developed drugs try to prevent infection by blocking the initial stage of fusion of HIVs envelope with the membrane of the target cell. However, in many instances HIV becomes resistant to drugs and individuals living with HIV have to regularly modify the particular combination of drugs they take. Why is HIV so persistent?
Root Causes That A Vaccine Cannot Cure
AIDS is clever. After all this time we still dont have a vaccine to prevent the virus. Thats not to say that developing prevention strategies hasnt kept people up at night.
Indeed, the inability to develop an effective vaccine has given rise to the field of HIV prevention medicine. This version of prevention relies on the use of anti-HIV treatment drugs to prevent an individual from either acquiring or transmitting HIV: stopping mother-to-child transmission test and treat to identify and medically manage people with HIV post-HIV exposure prophylaxis and pre-HIV exposure prophylaxis .
Unfortunately, this prevention approach, which relies on anti-HIV treatment drugs, creates additional anti-HIV treatment availability shortages and contributes to drug resistance already on the rise. Also, with the exception of PMTCT, anti-HIV drugs are not available to the vast majority of the global population.
I, and many others, have spent much of our adult lives trying to figure out how to prevent the spread of HIV in the absence of a vaccine, without relying on anti-HIV treatment drugs. I can say unequivocally that we have failed to put a significant dent in the number of new HIV cases that occur each year.
Its not that there havent been success stories along the way. Syringe exchange programs have been around for over 30 years, yet remain rare and underfunded. Condoms came out from under the covers and sparked a hunger for conversations about sex and sexuality.
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What Has Been Learnt So Far About How To Produce An Effective Hiv Vaccine
Vaccine researchers have learnt much from animal studies, from investigations of people who have been exposed to HIV without becoming infected, and from clinical trials of experimental HIV vaccines.
broadly neutralising antibodies
A neutralising antibody is an antibody that fully defends its target cell from an antigen. A broadly neutralising antibody is a neutralising antibody that has this effect against a wide range of antigens. A number of broadly neutralising antibodies have been isolated from persons living with HIV. Some of them are being studied and, in some cases, used in clinical trials, to defend humans against HIV infection, treat HIV infection, and kill HIV-infected CD4+ T cells in latent reservoirs.
Numerous approaches to vaccine design have been tested to learn more about how to protect against HIV and how to produce strong immune responses against HIV. Vaccine trials have investigated the following questions:
- How can a vaccine introduce HIV genes or proteins into the body safely?
- How many doses of vaccine are needed to make a strong immune response?
- Might a combination of vaccines, given in a specific sequence, produce a stronger response?
- What combination of HIV proteins produces the strongest response?
- How broad is the immune response does it work against all types of HIV?
- How long do the responses last?
So Why Is That So Hard To Do With Hiv
First of all, said Jefferys, lack of interest and funding are no longer really among the reasons. There was a period in the early 1990s when you could argue that HIV vaccine research was underfunded, he said. But by now, its a substantial budget. According to an analysis by the Resource Tracking for HIV Prevention Research & Development Working Group, a project of the HIV vaccine advocacy group AVAC, nearly $15.3 billion was spent on HIV vaccine research between 2000 and 2019. The money comes from philanthropic, public, and private groups like the Bill & Melinda Gates Foundation.
And if that money hasnt led yet to an effective vaccine, it has led to an enormous amount of information about both HIV and the immune system that led, in part, to the rapid development of COVID vaccines. HIV research helped reveal the importance of creating a vaccine using modified forms of invaders outer spike proteins to generate immune responses. HIV vaccine research also led to the perfection of mRNA as a vaccine method conceptused successfully for COVID, not so much for HIV.
Why the disparity? The short answer is that HIV is one of the wiliest, most slippery viruses known to modern science. And that answer breaks down into many factors.
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Why Cant Current Drugs Cure Hiv Infection
Until 1996, a diagnosis of HIV was a death sentence. Nearly all patients succumbed to AIDS within about 10 years after infection. But starting in that year, combination antiretroviral therapy, the so-called HIV cocktail, was introduced into clinical practice. It was one of the medical miracles of the 20th century.
HIV causes AIDS by infecting and killing a type of cell called a helper T cell, essential for a proper immune response to infectious agents. The slow but inexorable loss of these cells leaves the body unable to defend itself against a long list of bacteria and viruses, and it is infection with these opportunistic agents that eventually kills the patient.
HIV is a retrovirus, which means that it integrates its genetic information into a host cells own DNA. The viral DNA is then used by the host cell as if it were its own genes, and in turn directs the cell to make viral RNA , and more virus. In an untreated HIV infection, about a billion helper T cells are infected by the virus and killed every day, with an average time from infection to cell death of one to two days.
A small percentage of infected helper T cells do not die right away, but instead go into a resting, or latent, state in which the viral DNA they carrynow called a provirusis silent and no new RNA or virus is made.
If drug therapy is interrupted, the virus inevitably returns, and progression picks up where it left off at the time the patient started taking the drugs.
Status Of The Clinical Trial
On August 11, 2020, AGT announced approval by the FDA to begin Phase 1, the first human clinical trial for AGTs lead HIV program. AGT will conduct its Phase 1 study at clinical sites in the Baltimore/D.C. area. AGT expects that these sites will begin enrollment in the Fall of 2020.
AGT’s Phase 1 study clinicaltrials.gov identifier number is NCT04561258 and the study ID is AGT-HC168. For information about the ongoing Phase 1 study of AGT103-T, and information on the trial sites, click the button below.
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How Was A Covid
09 February 2021
As COVID-19 vaccination begins around the world, UNAIDS spoke to Peter Godfrey-Faussett, UNAIDS S
As COVID-19 vaccination begins around the world, UNAIDS spoke to Peter Godfrey-Faussett, UNAIDS Senior Science Adviser and Professor of International Health and Infectious Diseases at the London School of Hygiene and Tropical Medicine, about what is holding up an HIV vaccine.
Many people are asking, How was a COVID-19 vaccine found so quickly?
The SARS-CoV-2 virus, which is the virus that causes COVID-19, jumped from animals into humans in 2019. Whereas for HIV, that jump occurred 100 years ago in around the 1920s, and it became a problem in the 1980s when it started spreading among humans to a much greater extent.
The reason weve seen such a push on the COVID-19 vaccine is because of the urgency. In 2020, COVID-19 has infected almost 100 million people on the planet. COVID-19 has already killed 2 million people in 2020.
So, this urgency comes about, despite the fact that weve seen dramatic changes in everybodys life, with changes to travel and social distancing and masks and hand washing and sanitizer, and yet we’ve still seen a rapid rise in infections. This produces a huge urgency to make a vaccine. And, of course, it has a massive economic impact.
HIV and SARS-CoV-2 are quite different, right?
How much money is being invested in HIV vaccines?
COVID-19 has taken the headlineswhat about other infectious diseases?
Off Treatment And Still Undetectable
One approach to curing HIV is called treatment-free remission, or ART-free remission. This approach is also called a functional cure, because it would render HIV harmless without eliminating HIV from the body completely.
ART does a great job at eliminating HIV from the circulating blood of a PLWH, which is what keeps those on ART healthy and makes it impossible for those who are virally suppressed for at least six months to transmit HIV to their sexual partners . But even with viral suppression by ART, HIV remains hidden in a so-called HIV reservoir made up of immune system cells that contain HIV in the form of HIV DNA . Such HIV is called latent, because it hides from detection by the immune systemand these cells are called resting, because they are not actively producing new copies of the virus.
When latently infected, resting immune cells are reactivated, they begin to churn out new copies of fully active HIV. This explains why PLWH need to remain on ART throughout their entire lifeif ART stops, detectable virus comes back.
Finding ways to prevent the latent reservoir from becoming productive after stopping ART is thus a major focus of research into a cure for HIV today. This kind of sustained ART-free remission, sometimes called a functional cure, would allow a PLWH to keep latent virus suppressed without daily medication. Researchers are investigating a number of different strategies for achieving ART-free remission of HIV.
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If These Mrna Vaccines Are So Great Why Dont We Have One For Hiv Yet
Contributing Editor MicroPixieStock via Artem_Egorov via
One thing Ive heard a lot of in the past year or so from friends both IRL and on social media, is: How could we get multiple COVID-19 vaccines in less than a year, while weve known about HIV for nearly 40 years and we still dont have an HIV vaccine? The pharmaceuticals must be stopping it because theyre making too much money off the HIV drugs!
To which I always want to reply, Well, yes, its true, drugmakers do make a lot of money from HIV drugsabout $30 billion in 2020 alone , in factbut thats not the main reason we dont have an HIV vaccine yet. Making an HIV vaccine is really hard!
But then I always forget the details of exactly why its hard. But then I recently read about how drugmaker Moderna plans to take the mRNA technology they successfully applied to a vaccine for COVID and extend it to efforts at a vaccine for things like Zika, cancer, fluand, yes, HIV. So I decided to break down just why an HIV vaccine is so challenging.
I reached out to two terrific experts to do itRichard Jefferys, the Basic Science, Vaccines, and Cure Project director at Treatment Action Group , and Mark Feinberg, M.D., Ph.D., president and CEO of the International AIDS Vaccine Initiative , a nonprofit that develops vaccines and antibodies for HIV, tuberculosis, emerging infectious diseases, and neglected diseases.
Why Is Hiv So Evasive What Is The Hiv Reservoir
Although HIV can be controlled by antiretroviral therapy, it cannot be eliminated from the body. This is because HIV evades the normal immune system mechanisms for getting rid of cells infected by viruses.
HIV integrates itself into the DNA of human immune system cells and only replicates when the cell is stimulated to respond to an infection. These cells are called latently-infected cells. These cells are not recognised as infected by the immune system and killed off, allowing them to persist for as long as the cell lives.17
Some of the cells infected by HIV are very long-lasting memory T-cells. Reservoirs of latently- infected cells become established in the lymph nodes, the spleen and the gut. HIV also infects cells in the brain, but it is unclear if HIV can pass from the brain to other parts of the body. HIV may also persist for many years in macrophages immune cells found largely in tissues and in dendritic cells, which recognise infectious agents and alert other immune cells to remove them.
Latently-infected cells can proliferate without being activated and HIV may also pass from cell to cell within tissues in the gut and other reservoirs. 18 This means they evade the immune system and are not suppressed by antiretroviral drugs before infecting other cells.
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Millions With Hiv Die For Lack Of Access To Aids Drugs Mps Say
Millions of people with HIV die because they cannot get access to Aids drugs, according to a cross-party group of MPs.
As of this summer, 13.6 million people were taking combinations of antiretroviral drugs that keep HIV levels so low in the blood that people stay well and do not infect others.
But, says the all-party parliamentary group on HIV and Aids, that means two-thirds of adults with HIV, and three-quarters of the children, are not on treatment.
Its report says the global effort to get the drugs to children and adults in low and middle-income countries and save lives is still falling short, in part because of high prices charged by pharmaceutical companies and cuts in donor funding.
It is a modern tragedy of epic proportions, according to Pamela Nash, the MP who chairs the committee. This is a stark warning to governments, including the UK, that if we fail to address the barriers to access we will ultimately lose the battle to control and end the epidemic, she said.
The committees report, Access Denied, says it is expected that 55 million people will need HIV treatment by 2030. Last year, 1.5 million people died of HIV-related illnesses.
Two groups in particular are in jeopardy children, for whom there are inadequate drug formulations, and people who need second-line drug combinations because the basic first-line medicines have stopped working as drug resistance has set in.
People need to come before profits, she said