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Why Havent Researchers Developed An Hiv Vaccine Or Cure Yet
A blood test for analysis of HIV.
Last week, top experts on HIV/AIDS convened in Amsterdam for the 22nd International AIDS conference, and the mood was not great. Even though remarkable advances in treating HIV have led to effective management for many people living with the disease, and its overall incidence has declined, there are signs that the virus could make a troubling comeback.
“In a perfect world, we’d get a vaccine like the HPV vaccine that was 100% effective and I think that’s ultimately what we’re going to strive for.”
Growing resistance to current HIV drugs, a population boom in Sub-Saharan Africa, and insufficient public health resources are all poised to contribute to a second AIDS pandemic, according to published reports.
Already, the virus is nowhere near under control. Though the infection rate has declined 47 percent since its peak in 1996, last year 1.8 million people becamenewly infected with HIV around the world, and 37 million people are currently living with it. About 1 million people die of AIDS every year, making it the fourth biggest killer in low-income countries.
Leapsmag Editor-in-Chief Kira Peikoff reached out to Dr. Carl Dieffenbach, Director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, to find out what the U.S. government is doing to develop an HIV vaccine and cure. This interview has been edited and condensed for clarity.
What is the general trajectory of research in HIV/AIDS today?
How Does It Work
CCR5 is the most commonly used receptor by HIV-1 – the virus strain of HIV that dominates around the world – to enter cells.
But a very small number of people who are resistant to HIV have two mutated copies of the CCR5 receptor.
This means the virus cannot penetrate cells in the body it normally infects.
Researchers say it may be possible to use gene therapy to target the CCR5 receptor in people with HIV.
It is the same receptor the now jailed Chinese scientist He Jiankui worked on when he created the world’s first gene-edited babies.
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Why Is It So Difficult To Find An Hiv Cure
AGT, On:
More than 32 million people have died from AIDS-related illnesses since the start of the epidemic in 1981, making HIV/AIDS one of the greatest public health threats the world has known. Since it was first identified nearly 40 years ago, trillions of dollars have been spent by governments and private individuals on efforts to find effective treatments, vaccines, and a cure. The virus itself is surprisingly small and simple, and researchers know a great deal about the way HIV is contracted and makes its way through the body. However, to date, the only effective treatment is antiretroviral therapy , which halts the progress of the virus.
Its true that the use of ART has slowed the spread of HIV infection and reduced the number of deaths since the peak in 2004, there are still 38 million people living with HIV in the world today. While ART prevents AIDS and prolongs life in those infected with HIV, it does so at a significant cost in quality-of-life. In short, they are not a cure. With so great an effort on a global scale, why has it been so difficult to find an HIV cure?
Here are five reasons an HIV cure remains elusive:
Retrovirus & Mutation
T Cells
Latent Reservoirs
Cure vs Eradication
Differing Definitions of HIV Cure
AGT sponsored this article to highlight the importance of continuing HIV cure research until a cure is found. AGTs HIV Cure Program lead candidate for a functional cure is moving into clinical trials in 2020-2021.
Testing Hiv Vaccine Candidates
To date, there have been only a handful of clinical trials to test the efficacy of potential HIV vaccines in people. Of the six trials that scientists saw to completion, only one vaccine candidate proved effective at preventing infection.
That lone successful trial, known as RV144, used a prime-boost strategy in which participants received a total of six shots. The four prime jabs contained a canarypox virus that is incapable of replicating in cells and carries the genetic instructions for select HIV proteins. The participants cells make those viral proteins and develop an immune response against them.
Then participants also received two boosts, an injection of an HIV protein fragment that is essential for the virus to enter cells. The hope was that participants would develop a strong, wide-ranging immune response, giving those people broad protection against a variety of HIV subtypes.
Ultimately, that vaccine strategy lowered the risk of infection by 31.2 percent in vaccinated participants compared with the unvaccinated group. Although the shot showed only modest efficacy, those results changed the field by homing in on what type of immune response people needed to prevent infection, Zolla-Pazner says.
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Reported Cases Of Hiv Cure Or Remission
The first rigorously investigated case of a cure was Timothy Ray Brown, who underwent a stem cell transplant to treat leukaemia in 2006, stopped antiretroviral treatment during cancer treatment and has subsequently shown no trace of HIV on numerous highly sensitive tests. Researchers think he cleared HIV because the cancer treatment eliminated HIV-infected T-cells and the stem cell transplant repopulated his body with cells resistant to HIV infection. The stem cell donor had naturally occurring resistance to HIV infection due to the lack of CCR5 receptors on their immune system cells. Timothy Ray Brown died in 2020 following a recurrence of leukemia.
Researchers stress that these are unusual cases and attempts to replicate them in other people undergoing cancer treatment have failed to date. Stem cell transplants are risky for the recipient and not a suitable form of treatment for people without cancer.
remission
The disappearance of signs and symptoms of a disease, usually in response to treatment. The term is often used in relation to cancer, indicating that there is no evidence of disease, although the possibility of cancer remaining in the body cannot be ruled out. In HIV, remission is an alternative term for functional cure. A sustained ART-free remission would boost the immune system to induce long-term control of HIV, allowing a person living with HIV to maintain an undetectable viral load without daily medication.
Why Is It So Hard To Make An Hiv Vaccine
The history of HIV vaccine development has been marked by numerous setbacks and disappointments, with each apparent “breakthrough” presenting even more challenges and hurdles to overcome. Oftentimes it seems that for one step forward researchers take, an unforeseen obstacle sets them back by one and even two steps.
In some ways, its a fair assessment, given that we have yet to see a viable vaccine candidate. On the other hand, scientists have, in fact, made enormous strides in recent years, gaining greater insight into the complex dynamics of HIV infection and the bodys response to such infection. So stirring are these advances that some now believe a vaccine may be possible within the next 15 years .
Whether such a vaccine will be affordable, safe, and easy to administer and distribute to a worldwide population remains to be seen. But what we do know for sure is that a number of key barriers will need to be resolved if any such candidate will ever move beyond the proof-of-concept stage.
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Will There Ever Be A Cure For Hiv
Researchers and scientists believe we can find a cure for HIV. We know a lot about HIV, as much as certain cancers. Scientists are researching two types of cure: a functional cure and a sterilising cure.
There is no ‘natural cure’ or ‘herbal cure’ for HIV. Antiretroviral treatment is the only medication that is proven to effectively control HIV.
Ethical Considerations For Hiv Cure Research
The ethical principles that underpin trials exploring a cure for HIV infection, naturally pose another challenging requirement for scientists to meet.
Antiretroviral treatment is highly effective if taken consistently and side-effects of modern ART are limited. Treatment prevents onward transmission when taken consistently. People who started treatment fairly soon after infection are likely to have a near-normal life expectancy.
Against these well-established facts, participants in cure research trials especially those involving interruptions in ART need to be informed of the potential risks. Prolonged interruptions in treatment are associated with a higher risk of serious non-AIDS-defining illnesses such as heart disease in people with high viral load. The health implication of treatment interruptions in people who appear to be in remission are unknown. A treatment interruption may pose a risk of onward transmission if viral load rebounds suddenly. Potential treatments to clear the HIV reservoir or boost the immune system may have serious or unpredictable side-effects.
Participating in cure research may have psychological uncertainties, such as a concern about the risk of onward transmission to partners. Coming off ART in such trials may cause anxiety. Although a functional cure may deliver a remission from HIV treatment, people are still likely to test positive for HIV antibodies, so people would not consider themselves fully cured.49
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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.
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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Have There Been Any Breakthroughs
One reason to hope for a cure for HIV is that experimental treatments seem to have worked in a handful of people already.
The Berlin Patient: In 2008, a man with HIV named Timothy Ray Brown was effectively cured while living in Germany. Researchers treated his blood with a stem cell transplant for leukemia, but the treatment also cured his HIV. His stem cell donor carried a mutation of an HIV-related gene called CCR5. This mutation makes a person almost completely resistant to infection. Brown was the only person to be cured of HIV until 2019, when two others were effectively cured with a similar stem cell therapy.
Visconti Cohort: In 2010, a baby born with HIV in Mississippi began ART soon after birth and was in remission for 2 years after they stopped, but the virus did come back. A trial called the Visconti Cohort studied 20 people with HIV in France. They also started ART within weeks of infection. They were able to stop taking the drugs and still have low levels of HIV years later. Another trial of 15 children with HIV in Thailand had similar results. Itâs important to remember that these were controlled studies if you have HIV, you should never stop ART without talking to your doctor.
These are positive signs, but the studies are very small. We need more research on these potential cures to be able to develop treatments that would safely work on many people, not just a small number.
The Challenge Of The Replication Cycle
Instead of being able to focus on a single strain of HIV, researchers have to account for the fact that it replicates so quickly, which can cause mutations and new strains. The replication cycle of HIV takes a little more than 24 hours.
And while the replication process is fast, it’s not the most accurateproducing many mutated copies each time, which then combine to form new strains as the virus is transmitted between different people.
For example, in HIV-1 , there are 13 distinct subtypes and sub-subtypes that are linked geographically, with 15% to 20% variation within subtypes and variations of up to 35% between subtypes.
Not only is this a challenge in creating a vaccine, but also because some of the mutated strains are resistant to ART, meaning that some people have more aggressive mutations of the virus.
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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.
Treatment Reduces The Amount Of Hiv In The Blood
- The amount of HIV in the blood is called viral load.
- Taking your HIV medicine as prescribed will help keep your viral load low and your CD4 cell count high.
- HIV medicine can make the viral load very low . Viral suppression is defined as having less than 200 copies of HIV per milliliter of blood.
- HIV medicine can make the viral load so low that a test cant detect it .
- If your viral load goes down after starting HIV treatment, that means treatment is working. Continue to take your medicine as prescribed.
- If you skip your medications, even now and then, you are giving HIV the chance to multiply rapidly. This could weaken your immune system, and you could become sick.
- Getting and keeping an undetectable viral load is the best way to stay healthy and protect others.
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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.”
The Development Of Hiv Vaccines
HIV virions CDC Public Health Image Library
At a time when many infectious diseases were being brought or kept under control with global vaccination efforts in the 1990s, the human immunodeficiency virus , only identified in 1984, infected millions worldwide. From 1990 to 2014 the number of people living with HIV rose from 8 million to 36.9 million since the beginning of the HIV/Acquired Immune Deficiency Syndrome epidemic, AIDS has claimed more than 34 million lives.
HIV is a major public health concern not only because it cant yet be prevented by vaccination, but also because those it infects are infected for life with a virus that targets their immune system – making them more prone to other infections. The virus kills immune T helper cells called CD4+ cells, which are the coordinators of the human immune system. This is where the Acquired Immune Deficiency Syndrome name comes from: when HIV kills enough CD4+ cells, the infected persons immune system is unable to fight off infections it could ordinarily control. When the number of CD4+ cells drops below a certain point, a person is considered to have progressed from HIV infection to AIDS. People with AIDS are more susceptible to many types of infections, including those it could normally fight off, including types of pneumonia, tuberculosis, and shingles, as well as certain cancers.
This particular virus, however, poses unique challenges to vaccine development.
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