Tag Archives: hiv

The FDA finally approved a condom for anal sex. Here’s why it’s a good thing

Whether you’re in a committed relationship or prone to the throws of lust (or both, we’re not judging), you need to protect yourself and your partner — which usually means using a condom.

Still, as humans tend to be, we’re not always careful. We like to experiment, we sometimes falter — and pick up sexually-transmitted diseases (STDs). Whatever the reason, condoms are a great way to stay safe and can be used by people of the appropriate age just about anywhere–and they can also be lots of fun. Now, there’s a new type of condom on the block.

A victory for all genders and denominations

There’s never been an approved condom specifically for anal intercourse. Until now, condoms on the market were only approved for vaginal intercourse, which omits a large section of our society.

Condoms for vaginal sex currently on the market are recommended for use during anal or oral intercourse by the Center for Disease Control – meaning they’re legally backed by a drug agency for one activity and informally deemed effective for another in what is known as ‘off-label’ use. But the US Food and Drug Administration (USFDA) has finally approved the first condom for anal sex: the ONE Male Condom.

The approval is seen as a victory for sexual health and especially important for the LGBTQ community, who, until now, have not had a condom aimed specifically at them. Courtney Lias, director of the USFDA’s Office of GastroRenal, Obstetrics-Gynecological, General Hospital, and Urology Devices, says:

“The risk of STI transmission during anal intercourse is significantly higher than during vaginal intercourse. The FDA’s authorization of a condom that is specifically indicated, evaluated, and labeled for anal intercourse may improve the likelihood of condom use during anal intercourse.” 

What’s different with this condom

The newly approved condom is a natural rubber latex sheath that covers the penis. It’s available in three different versions: standard, thin and fitted. The fitted condoms, available in 54 different sizes, incorporate a paper template to find the best condom size for each user to minimize leakage. Global Protection Corp, which makes the condom, stresses that during anal intercourse, users should employ a compatible lubricant with their condom and all other brands.

“We want people to have lots of sex — but we also want them to be empowered and informed,” said Davin Wedel, president of Global Protection Corp.

Scientists studied the safety and efficacy of the condom in a clinical trial comprised of 252 men who prefer sex with men and 252 men who prefer intercourse with women. All volunteers were between 18 and 54 years of age. 

Results show the total condom failure rate was 0.68% for anal sex and 1.89% for vaginal intercourse. Researchers defined the condom failure rate as the number of slippages, breakage, or both slippage and breakage events over the total number of sex acts recorded in a diary by participants.

Disappointingly, the trial didn’t calculate the STD baseline as too many variables (such as not wearing a condom) could cause infection during the trial. Therefore, the rate of STDs was not measured at the beginning of the study and compared with later data. Despite this, the trial center did allow participants to self-report any genital-based infections which could have resulted from the use of a different condom brand before or during tests.

The researchers from Emory University who were behind the study said an essential reason for the trial’s success was that volunteers used lubricant, which prevents slippage and breakage, and the inclusion of instructions.

Taken together, these findings suggest that health bodies should provide lubricant along with the billions of condoms distributed as part of HIV and STD prevention efforts to minimize failure. 

The USFDA will help get more condoms like these on the market

The USFDA is responsible for controlling and supervising food, tobacco, dietary supplements, prescription drugs, blood transfusions, medical devices, cosmetics, and animal & veterinary products. They achieve this by inspecting manufacturing premises and reviewing the safety and effectiveness of a product before a business can sell it on the market after it has undergone extensive clinical trials that can last for over a decade.

A rigid classification, under the terms of a De Novo, the submitting company, must prove that their product presents a ‘medium risk’ to humans. In contrast, under the 510(k) submission, an organization only has to show their device presents no more risk to human health than the approved equivalent product – even where the marketed product has been deemed dangerous. De Novo submissions are also more expensive than the cheaper 510(k).

Surprisingly, even though the ONE condom is already approved by the USFDA using the flexible 510(k) category for vaginal sex, the agency has cleared the new product for anal sex through the De Novo pathway. This fact certainly raises questions regarding the lack of equivalency between condoms used for vaginal sex and anal sex.

On a positive note, they have established special controls so that other devices can now show equivalence to the ONE condom using a 510(k) classification to receive quicker clearance without the need for clinical trials. 

In its press release, the USFDA said the green light could pave the way for more condom makers to apply for faster approval if they show equivalent results. They add that they expect authorization of the ONE Male Condom to help reduce the transmission of STDs, including HIV/AIDS in both anal and vaginal intercourse.

All approved condoms are an easy way to protect yourself

Experts remind all sexually-active couples that they can still use other approved condoms on the market during anal sex:

“This isn’t a groundbreaking advancement in my opinion. All condoms can (and should!) be used to make anal sex safer, so just because this one brand has FDA approval doesn’t make it any better than other condom brands on the market,” says obstetrician-gynecologist and author Jennifer Lincoln who wasn’t part of the trial, for PopSci. “Don’t let the ‘FDA approved’ label sway you when you are at the grocery store—the best condom to use for safe sex is the one you have access to and the one you will actually use.”

Still, this is a galvanizing moment for the LGBTQ movement.

“This authorization helps us accomplish our priority to advance health equity through the development of safe and effective products that meet the needs of diverse populations. This De Novo authorization will also allow subsequent devices of the same type and intended use to come to the market through the 510k pathway, which could enable the devices to get on the market faster,” Lias added in the USFDA statement.

It remains to be seen whether this will trigger a longer-term movement. In the meantime, stay safe.

The fascinating science behind the first human HIV mRNA vaccine trial – what exactly does it entail?

In a moment described as a “potential first step forward” in protecting people against one of the world’s most devastating pandemics, Moderna, International AIDS Vaccine Initiative (IAVI), and the Bill and Melinda Gates Foundation have joined forces to begin a landmark trial — the first human trials of an HIV vaccine based on messenger ribonucleic acid (mRNA) technology. The collaboration between these organizations, a mixture of non-profits and a company, will bring plenty of experience and technology to the table, which is absolutely necessary when taking on this type of mammoth challenge.

The goal is more than worth it: helping the estimated 37.7 million people currently living with HIV (including 1.7 million children) and protecting those who will be exposed to the virus in the future. Sadly, around 16% of the infected population (6.1 million people) are unaware they are carriers.

Despite progress, HIV remains lethal. Disturbingly, in 2020, 680,000 people died of AIDS-related illnesses, despite inroads made in therapies to dampen the disease’s effects on the immune system. One of these, antiretroviral therapy (ART), has proven to be highly effective in preventing HIV transmission, clinical progression, and death. Still, even with the success of this lifelong therapy, the number of HIV-infected individuals continues to grow.

There is no cure for this disease. Therefore, the development of vaccines to either treat HIV or prevent the acquisition of the disease would be crucial in turning the tables on the virus.

However, it’s not so easy to make an HIV vaccine because the virus mutates very quickly, creating multiple variants within the body, which produce too many targets for one therapy to treat. Plus, this highly conserved retrovirus becomes part of the human genome a mere 72 hours after transmission, meaning that high levels of neutralizing antibodies must be present at the time of transmission to prevent infection.

Because the virus is so tricky, researchers generally consider that a therapeutic vaccine (administered after infection) is unfeasible. Instead, researchers are concentrating on a preventative or ‘prophylactic’ mRNA vaccine similar to those used by Pfizer/BioNTech and Moderna to fight COVID-19.

What is the science behind the vaccine?

The groundwork research was made possible by the discovery of broadly neutralizing HIV-1 antibodies (bnAbs) in 1990. They are the most potent human antibodies ever identified and are extremely rare, only developing in some patients with chronic HIV after years of infection.

Significantly, bnAbs can neutralize the particular viral strain infecting that patient and other variants of HIV–hence, the term ‘broad’ in broadly neutralizing antibodies. They achieve this by using unusual extensions not seen in other immune cells to penetrate the HIV envelope glycoprotein (Env). The Env is the virus’s outer shell, formed from the cell membrane of the host cell it has invaded, making it extremely difficult to destroy; still, bnAbs can target vulnerable sites on this shell to neutralize and eliminate infected cells.

Unfortunately, the antibodies do little to help chronic patients because there’s already too much virus in their systems; however, researchers theorize if an HIV-free person could produce bnABS, it might help protect them from infection.

Last year, the same organizations tested a vaccine based on this idea in extensive animal tests and a small human trial that didn’t employ mRNA technology. It showed that specific immunogens—substances that can provoke an immune response—triggered the desired antibodies in dozens of people participating in the research. “This study demonstrates proof of principle for a new vaccine concept for HIV,” said Professor William Schief, Department of Immunology and Microbiology at Scripps Research, who worked on the previous trial.

BnABS are the desired endgame with the potential HIV mRNA vaccine and the fundamental basis of its action. “The induction of bnAbs is widely considered to be a goal of HIV vaccination, and this is the first step in that process,” Moderna and the IAVI (International AIDS Vaccine Initiative) said in a statement.

So how exactly does the mRNA vaccine work?

The experimental HIV vaccine delivers coded mRNA instructions for two HIV proteins into the host’s cells: the immunogens are Env and Gag, which make up roughly 50% of the total virus particle. As a result, this triggers an immune response allowing the body to create the necessary defenses—antibodies and numerous white blood cells such as B cells and T cells—which then protect against the actual infection.

Later, the participants will also receive a booster immunogen containing Gag and Env mRNA from two other HIV strains to broaden the immune response, hopefully inducing bnABS.

Karie Youngdahl, a spokesperson for IAVI, clarified that the main aim of the vaccines is to stimulate “B cells that have the potential to produce bnAbs.” These then target the virus’s envelope—its outermost layer that protects its genetic material—to keep it from entering cells and infecting them.  

Pulling back, the team is adamant that the trial is still in the very early stages, with the volunteers possibly needing an unknown number of boosters.

“Further immunogens will be needed to guide the immune system on this path, but this prime-boost combination could be the first key element of an eventual HIV immunization regimen,” said Professor David Diemert, clinical director at George Washington University and a lead investigator in the trials.

What will happen in the Moderna HIV vaccine trial?

The Phase 1 trial consists of 56 healthy adults who are HIV negative to evaluate the safety and efficacy of vaccine candidates mRNA-1644 and mRNA-1644v2-Core. Moderna will explore how to deliver their proprietary EOD-GT8 60mer immunogen with mRNA technology and investigate how to use it to direct B cells to make proteins that elicit bnABS with the expert aid of non-profit organizations. But readers should note that only one in every 300,000 B cells in the human body produces them to give an idea of the fragility of the probability involved here.

Sensibly, the trial isn’t ‘blind,’ which means everyone who receives the vaccine will know what they’re getting at this early stage. That’s because the scientists aren’t trying to work out how well the vaccine works in this first phase lasting approximately ten months – they want to make sure it’s safe and capable of mounting the desired immune response.

And even though there is much hype around this trial, experts caution that “Moderna are testing a complicated concept which starts the immune response against HIV,” says Robin Shattock, an immunologist at Imperial College London, to the Independent. “It gets you to first base, but it’s not a home run. Essentially, we recognize that you need a series of vaccines to induce a response that gives you the breadth needed to neutralize HIV. The mRNA technology may be key to solving the HIV vaccine issue, but it’s going to be a multi-year process.”

And after this long period, if the vaccine is found to be safe and shows signs of producing an immune response, it will progress to more extensive real-world studies and a possible solution to a virus that is still decimating whole communities.

Still, this hybrid collaboration offers future hope regarding the prioritization of humans over financial gain in clinical trials – the proof is that most HIV patients are citizens of the third world.

As IAVI president Mark Feinberg wrote in June at the 40th anniversary of the HIV epidemic: “The only real hope we have of ending the HIV/AIDS pandemic is through the deployment of an effective HIV vaccine, one that is achieved through the work of partners, advocates, and community members joining hands to do together what no one individual or group can do on its own.”

Whatever the outcome, money is no longer a prerogative here, and with luck, we may see more trials based on this premise very soon.

‘Kick and kill’ approach cures HIV in 40% of mice

New research on mice is paving the way against the human immunodeficiency virus (HIV), the cause of AIDS.

Image via Pixabay.

Although the team did not manage to completely eliminate the virus from all the mouse hosts, they showcase an effective way of engaging with it. According to the results, the approach eliminated the virus from 40% of the mice used in the study. With more work to perfect it, such an approach could one day form the basis of an effective and reliable treatment against HIV.

Cornerstone

Currently, people infected with HIV have the option of using antiretroviral therapy to slow down the virus’ progression. However, we have no way to attack the pathogen and clear it out of a victim’s body. HIV can infect human immune cells — helper T cells, or ‘CD4+ T’ cells, to be precise — and lay dormant within them. Although our bodies have the ability to destroy HIV, this process leaves it hidden and protected from our immune response — because it’s in the cells that largely direct that response.

Any effective strategy against the virus, then, should start with forcing the virus out of hiding. This is the first part of the so-called “kick and kill” strategy, which was piloted by the same researchers that led the present study — a team at the University of California, Los Angeles — back in 2017.

In the last few years, the team has refined their approach. In 2017, they were able to clear HIV from 25% of the mice they worked with; in the present study, they report eliminating it from 40% of the mice, an almost double success rate.

The process involved first administering antiretrovirals to the mice, together with a synthetic molecule known as SUW133. This duo forces HIV out of the cells it is hiding in throughout the body. SUW133 in particular works to activate the virus in infected cells; up to one quarter of infected cells died during the time SUW133 forced this activation process to happen, the team explains.

The next step consisted of giving the treated mice injections with natural, healthy cytotoxic T white cells, which would go on and kill infected cells and virus particles.

In order to test the effectiveness of their approach, the team investigated the spleens of each mice. This organ is a common hiding place for HIV-positive cells. If no HIV was detected here, the team concluded that it had been successfully eliminated from the animal’s body.

The team notes that the compounds above worked better in combination than they did when administered independently.

Their goal for the future is to eliminate HIV from all the mice in their experiments and then progress their research into the preclinical stage by performing the same procedure on nonhuman primates, which better resemble human biology.

As of 2020, 38 million people worldwide are infected with HIV, and almost 36 million have already lost their lives to AIDS and related complications.

The paper “Latency reversal plus natural killer cells diminish HIV reservoir in vivo” has been published in the journal Nature Communications.

STEM cells could lead the way towards an effective cure against HIV/AIDS

Stem cells might finally give us the tools to fight off the human immunodeficiency virus (HIV), the pathogen responsible for AIDS, according to a new paper. Although the findings are still quite early, and based on an animal model, the authors are confident that the findings will translate well to human biology.

Image credits Miguel Á. Padriñán.

Researchers at the University of California Davis report that a specialized type of stem cell — mesenchymal stem cells (MSCs) — can boost the body’s immune response against SIV, the simian immunodeficiency virus, in primates. SIV is the equivalent of HIV but only infects non-human primates.

The discovery, they explain, makes it possible for us to establish a realistic roadmap for a multi-pronged HIV eradication strategy.

STEMing the infection

“Impaired immune functions in HIV infection and incomplete immune recovery pose obstacles for eradicating HIV,” said Satya Dandekar, senior author of the paper and the chairperson of the Department of Medical Microbiology and Immunology at UC Davis. “Our objective was to develop strategies to boost immunity against the virus and empower the host immune system to eradicate the virus”.

“We sought to repair, regenerate, and restore the lymphoid follicles that are damaged by the viral infection.”

Lymphoid tissue in the gut is a key site for HIV replication during the early stages of an infection, the team explains, and later forms viral reservoirs that make removing the pathogen very difficult. Previous research has shown that once it gets a foothold here, HIV causes a severe decrease in immune cells in the gut’s mucosal tissues (its lining) and attacks its epithelial barrier lining, causing a leaky gut.

This lymphoid tissue houses structures known as follicles, whose job is to mount long-term counterattacks against pathogens in our bodies by producing antibodies against them. This, unfortunately, means that an HIV infection impairs the same structures that are meant to defeat it.

Antiretroviral drugs are effective in suppressing HIV’s ability to replicate, but they don’t repair the damage the virus already caused to these follicles. So they can keep the infection suppressed, but on their own, they can’t form an efficient treatment against the disease.

However, the team reports that bone marrow-derived MSCs can. They carried out their experiment using a rhesus macaque model that had impaired immunity and disrupted gut functions due to an SIV infection. These cells were able to modulate, alter, and remodel the damaged mucosal site — in essence, they could repair the virus-caused damage.

“We are starting to recognize the great potential of these stem cells in the context of infectious diseases. We have yet to discover how these stem cells can impact chronic viral infections such as AIDS,” Dandekar said.

Following the procedure, the authors saw a rapid rise in antibodies and immune T cell levels, both of which engaged with the infection.

Ideally, such approaches would be used in conjunction with current HIV treatments. They can repair our bodies’ natural defenses, while antiretroviral compounds keep the infection in check. That being said, the MSCs were able to improve the hosts’ response against the infection even by themselves.

The paper “Gut germinal center regeneration and enhanced antiviral immunity by mesenchymal stem/stromal cells in SIV infection” has been published in the journal JCI Insight.

We finally have a vaccine that works against HIV (in early tests)

Hope against HIV, the human immunodeficiency virus, is closer than any time before. A new vaccine against this virus has shown promise in Phase 1 trials, leading to the production of efficient antibodies in 97% of participants.

Image credits Asian Development Bank / Flickr.

HIV and AIDS, the condition it causes, are undoubtedly some of the most terrifying medical diagnoses one can hear today. Not only the horrendous symptoms, but also the fact that they’re incurable, make them so. But perhaps not incurable for much longer, as new research shows a promising way forward against this deadly disease and the pathogen that causes it.

Immunity at last

“We and others postulated many years ago that in order to induce broadly neutralizing antibodies (bnAbs), you must start the process by triggering the right B cells – cells that have special properties giving them potential to develop into bnAb-secreting cells,” explained Dr William Schief, a professor and immunologist at Scripps Research and executive director of vaccine design at IAVI’s Neutralizing Antibody Center, where the vaccine was developed.

“In this trial, the targeted cells were only about one in a million of all naïve B cells. To get the right antibody response, we first need to prime the right B cells. The data from this trial affirms the ability of the vaccine immunogen to do this.”

This vaccine, the product of a collaboration between the Scripps Research institute and non-profit IAVI draws on a novel vaccination approach to help patients develop antibodies against HIV. This approach involves triggering “naive B cells” in our bodies to produce broadly neutralizing antibodies that, in turn, fight the pathogen. It is hoped that these ‘bnAbs’ can attach to proteins called spikes alongside the surface of the HIV virus. These spikes stay very similar in structure and function across different strains of the pathogen, meaning the vaccine could be broadly efficient against it.

This ability to function across strains is a major selling point of this vaccine. HIV affects over 38 million people worldwide but a cure has not yet been forthcoming because the virus has a very fast mutation rate, meaning it can adapt to our immune system and traditional treatment approaches.

The vaccine is meant to be the first in a multi-step vaccination program that aims to coax our bodies into producing a wide range of bnAbs’s, potentially helping against other viruses that have been eluding us so far, according to Europeanpharmaceuticalreview.

The Phase 1 trial included 48 healthy adults who received either a placebo or two doses of the vaccine compound along with an adjuvant developed by GlaxoSmithKline. By the end of the trial, 97% of the participants in experimental groups (i.e. that didn’t receive a placebo) had the desired type of antibody in their bloodstream.

This is the first time we’ve been successful in inducing secretion of broadly-neutralizing antibodies against HIV, the team explains, with lead investigator Dr. Julie McElrath, senior vice president and director of Fred Hutch’s Vaccine and Infectious Disease Division calling it “a landmark study in the HIV vaccine field”.

“This study demonstrates proof of principle for a new vaccine concept for HIV, a concept that could be applied to other pathogens as well,” says Dr Schief.

“With our many collaborators on the study team, we showed that vaccines can be designed to stimulate rare immune cells with specific properties and this targeted stimulation can be very efficient in humans. We believe this approach will be key to making an HIV vaccine and possibly important for making vaccines against other pathogens.”

Needless to say, since this was only a Phase 1 trial, we’re still a considerable way away from seeing this vaccine in a shot. However, the results do pave the way towards a Phase 2, and (hopefully) a Phase 3 for the drug. For the next step, the team is going to collaborate with biotechnology company Moderna to develop and test an mRNA-based vaccine for the same task as their current compound — if successful, this would considerably speed up the process.

Still, for now, the compound works as a proof of concept. It shows that our immune systems can be primed and prepared to face even terrifying pathogens. “This clinical trial has shown that we can drive immune responses in predictable ways to make new and better vaccines, and not just for HIV. We believe this type of vaccine engineering can be applied more broadly, bringing about a new day in vaccinology,” concludes said Dr. Dennis Burton, professor and chair of the Department of Immunology and Microbiology at Scripps Research, scientific director of the IAVI Neutralizing Antibody Center and director of the NIH Consortium for HIV/AIDS Vaccine Development.

The same approach can also be used to try and create new vaccines for other stubborn diseases like influenza, dengue, Zika, hepatitis C, and malaria, the team adds.

New injectable drug both prevents and treats HIV infections

Credit: Pixabay.

Researchers affiliated with the University of Utah have devised a peptide-based injectable drug that prevents HIV from infecting cells. Unlike other drugs available on the market, the novel therapy offers long-lasting protection and has few side effects. Experiments on non-human primates also showed that the drug can be used to dramatically reduce the amount of HIV circulating in the bloodstream when the infection is already present. 

“This is an exciting new HIV therapeutic option for both prevention and treatment, with a unique mechanism of action compared to other approved drugs,” Michael S. Kay, a senior author of the study and a professor of biochemistry at the University of Utah, said in a statement. “It has great potential to help patients who suffer from drug resistance as well as those who would benefit from a longer-acting, injectable anti-HIV drug cocktail.”

Better preventive medicine for HIV?

The human immunodeficiency virus (HIV) is one tough nut to crack. Its M.O. is to attack the very immune cells that are designed to target invaders such as HIV. When enough of these T helper cells are destroyed by the virus, the body is defenseless against HIV itself, as well as other infections. When this happens, the HIV-infected person develops acquired immune deficiency syndrome (AIDS).

Scientists first discovered HIV and AIDS in the early 1980s. By 1987, there were 32,000 people infected with HIV in the United States alone, more than half of whom had died.

Today, there are more than 38 million people currently living with the infection. Fortunately, these people can now take modern antiretroviral therapy (cART), a cocktail of drugs that dramatically enhance survivability and prevent the onset of AIDS. HIV drugs also stop people who have the virus from passing it to their partner during sex.

On the flipside, cART is very expensive, can have serious side effects that negatively impact quality of life, and requires patients to take pills daily.

While it’s remarkable that we now have drugs that can manage HIV infections, there’s always room for improvement. And Kay and colleagues believe their new HIV therapy is a promising avenue of research.

Their therapy is based on a drug called CPT31, which is based on D-peptides that target a crucial mechanism in the HIV fusion machinery that rarely mutates.

Proteins and most naturally occurring peptides are composed of amino acids in the L-configuration. D-peptides are basically the mirror version of L-peptides, sort of like your left hand and right hand — they’re both the same but in different configurations.

Since D-peptides are so analogous to natural peptides, they are largely ignored by the immune system, preventing unwanted immune reactions that are often a side effect of traditional HIV drugs. Additionally, CPT31 lasts longer in the body compared to natural peptides, making them particularly suitable for long-acting injectable formulations.

“As a D-peptide, our hope is that CPT31 will provide extended viral suppression with a lower dose and reduced side effects,” said Brett Welch, a co-author of the study and senior director of technology and strategy at Navigen, Inc., the company that manufacturing CPT31 and is currently managing upcoming clinical trials.

The researchers injected CPT31 into healthy macaque monkeys several days prior to exposing them to a hybrid simian-human form of HIV called SHIV. Although the monkeys were exposed to a very high dose of SHIV, they never developed any obvious signs of infection.

These experiments allowed the researchers to determine the minimum dose of CPT31 that is required for effective therapy, which will help inform upcoming clinical trials.

“We think this drug could be used by itself to prevent HIV infection because initial HIV exposure typically involves a relatively small amount of virus,” Kay says. “This study showed that the vast majority of circulating HIV strains from around the world are potently blocked by CPT31.”

Additionally, the researchers also injected CPT31 into monkeys that were already infected with SHIV and had received no prior treatment. Over the span of 30 days, the drug significantly lowered the presence of SHIV in the bloodstream. Unfortunately, the viral levels rebounded two to three weeks after the shot was administered.

“Such a simplified ‘maintenance therapy’ could present patients with a new option for viral control that is more cost-effective, convenient to take, and has fewer side effects,” Kay says.

Navigen is also working on a longer-acting formulation of CPT31. The goal is to have people take an injection once every three months.

 “Long-acting injectable formulations appear to be greatly preferred by both patients and physicians compared to current daily drug regimens that can be challenging to maintain,” Welch says. “Additionally, the steady therapeutic drug levels provided by such a formulation would reduce the risk of drug resistance caused by missed daily pills, as well as reduce side effects.”

The findings appeared in the Proceedings of the National Academy of Sciences (PNAS).

Scanning electron microscope image of a human immunodeficiency virus (HIV-1). Credit: Public Domain.

HIV sequencing from archived tissue suggests the virus crossed to humans in early 1900s

Scanning electron microscope image of a human immunodeficiency virus (HIV-1). Credit: Public Domain.

Scanning electron microscope image of a human immunodeficiency virus (HIV-1). Credit: Public Domain.

The general consensus is that HIV crossed from chimps to humans at some point in the 1920s in what is now the Democratic Republic of Congo. Experts believe this happened as a result of people hunting and eating chimps carrying the Simian Immunodeficiency Virus (SIV), a virus closely related to HIV. A new study performed by researchers at the University of Arizona confirms this timeline after extracting a nearly complete genetic sequence of an HIV virus from a 50-year-old lymph node.

The tissue belonged to a 38-year-old man in what is now the Democratic Republic of Congo and had been sealed with paraffin inside a repository at the University of Kinshasa for decades. For the last five years, Michael Worobey and colleagues at the University of Arizona have been working to extract the genetic sequence from the HIV-1 virus found in the tiny lymph node. it’s the oldest genetic code for HIV-1 that scientists have recovered thus far, making a decade older than the previous record holder.

Sequencing a complete genome from an archived tissue is an impressive technical feat. Only a decade ago, Worobey and colleagues were able to extract a mere fragment of HIV RNA — not the whole genetic code — from the lymph node belonging to a 60-year-old woman in 1960. Since then, the researchers have been fine-tuning their method to extract even more information.

According to the study, which hasn’t yet been peer-reviewed but which is publicly available on the preprint server bioRxviv, the HIV virus was already extremely genetically diverse in 1960. This means that the viruses had already been transmitting among humans for a while. The only way this could have happened is if the virus had at least a couple of decades to evolve prior to 1960. Ultimately, the researchers concluded that based on these viral sequences, HIV must have diverged from a common source in the early 1900s or perhaps in the late 1800s.

” Inferring the precise timing of the origin of the HIV/AIDS pandemic is of great importance because it offers insights into which factors did—or did not—facilitate the emergence of the causal virus. Previous estimates have implicated rapid development during the early 20th century in Central Africa, which wove once-isolated populations into a more continuous fabric. We recovered the first HIV-1 genome from the 1960s, and it provides direct evidence that HIV-1 molecular clock estimates spanning the last half-century are remarkably reliable. And, because this genome itself was sampled only about a half-century after the estimated origin of the pandemic, it empirically anchors this crucial inference with high confidence,” the authors wrote.

 

End of AIDS in sight — existing treatment prevents transmission of HIV

A groundbreaking advancement has been made in the fight against HIV: a study on HIV-carrying men found that the risk of viral transmission is zero if the virus is suppressed by antiretrovirals. The study suggests that offering proper treatment to everyone carrying HIV would end virtually all HIV transmission.

HIV-infected T cell. Image credits: NIAID.

The landmark European study followed nearly 1,000 gay male couples, where one partner had HIV and the other was taking antiretroviral drugs to suppress it. The couples had sex without condoms or other forms of protection. After eight years of medical checks and follow-ups, the study found no HIV transmission at all within couples.

A key point of the study was the fact that it did find HIV infections in 15 men among the 972 gay couples, but genetic analysis showed that their infections were with strains of HIV from another sexual partner. In other words, people did contract HIV, but only from partners who had not taken the antiretroviral treatment.

“Our findings provide conclusive evidence for gay men that the risk of HIV transmission with suppressive ART is zero,” said Alison Rodger, a professor at University College London who co-led the research.

Rodgers could barely contain her enthusiasm for the results, saying that it represents a huge step forward for HIV-infected people.

“It’s brilliant – fantastic. This very much puts this issue to bed,” said Prof Alison Rodgers from University College London, the co-leader of the paper published in the Lancet medical journal.

“This powerful message can help end the HIV pandemic by preventing HIV transmission, and tackling the stigma and discrimination that many people with HIV face,” she continued.

Of course, while this shows that an end to HIV transmissions might be in sight, actually achieving that goal is a whole different ball game. HIV and AIDS are currently in a rather weird phase. Since the epidemic began in the 1980s, more than 77 million people have become infected with HIV, and almost half of them have been killed by it. There is no true cure to eliminate the virus, but antiretroviral treatments have become very efficient at keeping it under control. Out of the people taking proper treatment, 97% have an undetectable level of the virus, meaning they cannot pass it further. However, the number of new infections stubbornly remains at around 1.8 million cases worldwide per year. Furthermore, there are significant concerns regarding the virus potentially developing resistance to current treatments.

It seems that HIV might be entering a make-or-break phase. While this study offers renewed hope to contain the virus, there’s still a long way to go and we need sustained efforts to be able to finally deal with this devastating virus.

HIV + tuberculosis, a deadly combination, affects over 1 million people

Some 1.2 million people worldwide are infected with both viruses. Now, researchers describe a new mechanism through which these viruses help each other, posing greater risks for patients.

Nanotubes linking two macrophages in humans infected with HIV-1 in a TB-associated micro-environment. Image credits: Shanti Souriant.

Throughout the centuries, tuberculosis has been present in many different countries and geographic areas. There is evidence that the pharaoh Akhenaten and his wife Nefertiti both died from tuberculosis, and anthropological studies at a site in Germany have shown that the disease affected people since the Neolithic. Tuberculosis became much more prevalent with the increase of urbanization, and at the end of the 19th century, it was one of the most urgent health problems. Thankfully, advances in treatment, vaccination, and overall sanitation drastically reduced the impact of tuberculosis — although the disease still remains highly prevalent, infecting 10 million people every year and killing 1.6 million in 2017.

Meanwhile, HIV spread dramatically during colonialist times in the 20th century. Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, but with modern antiretroviral treatment, HIV rarely progresses to AIDS, and is regarded as a generally manageable condition in the developed world. It is still one of the most dangerous viruses in the world.

As if having one of the two viruses wasn’t bad enough, quite a lot of people have both — 1.2 million, according to an international team led by researchers at the CNRS and Inserm. The team also reports that in this case, the two viruses work together to do even greater damage than they would individually.

In the presence of tuberculosis, HIV-1 (the most widespread form of HIV) moves from one cell to another via nanotubes which form between macrophages, drastically increasing the percentage of infected cells.

Macrophages, a type of cell in the immune system that engulfs and digests unwanted pathogens, can serve as hosts for both tuberculosis and HIV-1 (the most widespread form of HIV). In the presence of tuberculosis, macrophages form tunnel-like nanotubes, which HIV can use to transfer from one cell to another, drastically increasing the percentage of infected cells.

This also produced a snowball effect: the more severe the TB, the more nanotubes were formed, which allowed HIV to infect more cells, generating more macrophages, more nanotubes, and so on.

But there is a silver lining to all this: the specific type of macrophage can be assessed through soluble markers in the blood, which means that diagnosis and treatment of patients suffering from both illnesses can be facilitated. Scientists were also able to use existing treatment to inhibit the formation of these macrophages, thus reducing viral transfer and HIV-1 production.

The study “Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages” has been published in Cell.

 

A third patient might also be HIV-free

After the Berlin Patient and the London Patient, a third patient might also be HIV-free following a transplant: the Düsseldorf patient.

HIV Free

More than 10 years ago, medical researchers in Berlin made headlines with the announcement that for the first time in history, an HIV patient appeared to have been virus free following a stem cell transplant (via bone marrow) meant to treat a separate condition — leukemia.

Since then, no one has ever managed to eliminate the HIV virus until very recently: a few days ago, researchers announced that another patient, this time in London, also managed to get rid of the virus, also following a stem cell transplant meant to treat a different condition. Although doctors were skeptical to use the word ‘cure’, the second patient has been HIV-free for 18 months and counting.

Credits: NIH.

Now, a separate group of researchers has announced a third instance: the Düsseldorf patient. The Düsseldorf patient has been announced at the Conference on Retroviruses and Opportunistic Infections in Seattle. This patient has only been HIV-free for 3.5 months and therefore calls for even more skepticism. However, being off of antiviral drugs and HIV-free is still a promising accomplishment, even if more time is necessary for proper confirmation.

A cure?

With three patients becoming HIV-free after undergoing the same type of transplant, this is no longer a coincidence and the word cure flows almost naturally — but this is by no means a scalable treatment.

There are several common denominators for all three patients, all of which offer little in the way of scalability. For starters, there are two main variants of HIV, one of which is much rarer than the other — and all three patients had the rare variant. Secondly, they were all ‘cured’ following a bone marrow transplant, which is not only difficult and painful but also very risky. The three patients suffered from another serious condition which justified the bone marrow transplant. Most HIV patients are not suitable at all for a bone marrow transplant — it’s usually recommended as a last-ditch effort to fight cancer. Lastly, the marrow donors had a particular mutation which eliminated HIV’s ability to attach to host cells.

Essentially, the HIV patients needed the bone marrow transplant to fight cancer, not HIV — and they got really lucky. This is not a large scale cure by any means. But that doesn’t mean that researchers can’t use these rare cases and adapt them.

Invigorating the HIV fight

There have been many advancements in the fight against HIV, but there’s still no cure in sight. The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs in an attempt to keep the infection at bay. This has been successful in most parts of the world, dramatically increasing HIV survivability. HIV has become a chronic condition in which progression to AIDS is increasingly rare.

However, there are also growing concerns regarding current treatments. Drug resistance is one of the main concerns. Some viruses have exhibited the natural ability to develop drug-resistance and people not taking antiretrovirals properly can help speed up that process and pass drug-resistant strains to others. The drugs can also have serious negative side effects.

Lastly, while treatment costs have gone down dramatically, cost is still a crucial issue in some parts of the world. For instance, combination therapy has been introduced in South Africa for as little as $10 per patient per month, but a similar treatment might cost over $20,000 in the US, and countries that need the treatment the most are least able to afford it.

So researchers hope that they can learn something from these rare cases and adapt it to a scalable treatment. Replicating the HIV-eradicating effects seen in the Berlin Patient has been attempted several times, but confirmation has been lacking until now. It’s still early days, but with the results being confirmed, this opens up a promising avenue for finally eliminating HIV. We’re not there yet, but we’re zooming in.

There are currently around 37 million people living with HIV worldwide, and the virus claims around 1 million lives annually.

Defeating HIV: second patient in history goes into sustained remission after stem cell transplant

After the famous ‘Berlin patient’ ten years ago, a second person has now experienced remission from HIV. After a stem cell transplant (intended to treat cancer), the patient appeared to be HIV-free and has remained so for 18 months so far. The patient, whose case is presented in the journal Nature, is a man in the UK who has chosen to remain anonymous.

It’s a case of the “happy side effect” in a very unfortunate situation: after the patient was diagnosed with HIV in 2002, he was also diagnosed with advanced Hodgkin’s lymphoma in 2012. To treat the cancer, researchers at the University of Cambridge and University of Oxford carried out a stem cell transplant. However, just like in the case of the ‘Berlin patient’, the stem cell transplant came from donors with a protein mutation known as CCR5. HIV uses the protein to enter immune cells, but the mutated version renders the virus unable to attach itself to the cell walls — essentially protecting the body from the HIV.

The transplant proceeded without major complications. The patient also underwent chemotherapy, which can be somewhat effective against HIV as it kills cells that are dividing, but the key aspect here is the CCR5 receptor, which prevents HIV from rebounding after the treatment.

After 18 months, the patient appeared to be virus-free, although researchers are still skeptical of using the word ‘cured’.

It’s still only a sample size of two, but it’s the first time the ‘Berlin patient’ results have been replicated.

“By achieving remission in a second patient using a similar approach, we have shown that the Berlin Patient was not an anomaly, and that it really was the treatment approaches that eliminated HIV in these two people,” said the study’s lead author, Professor Ravindra Gupta (UCL, UCLH and University of Cambridge).

The study is even more exciting as reactions from the research community were very positive.

“This is good quality research and the authors used the best available technology to demonstrate with the highest degree of certainty currently possible that the patient is free of the virus,” says Prof. Áine McKnight, Professor of Viral Pathology at Queen Mary University of London.

“This is a highly significant study. After a ten year gap it provides important confirmation that the ‘Berlin patient’ was not simply an anomaly.”

Unfortunately, this is not really a scalable treatment option for HIV. Large-scale stem cell transplants would be impractical and risky. However, it represents something that might be incorporated into future treatments. Some teams are examining whether gene-therapy techniques to induce mutations on the immune system could be an option. However, there are also considerable risks, particularly when it comes to affecting other genes in detrimental ways.

Furthermore, the patient had a rare variant of HIV. There are two main variants: one uses the CCR5 co-receptor and the other uses the CXCR4 co-receptor. The vast majority of cases are in the first category, whereas this British patient fell in the second category.

“The authors clearly point out that the technique will not necessarily be effective for all HIV infected individuals, specifically those infected with CXCR4 viruses. However, the principal of targeting co-receptors may be of universal benefit,” adds McKnight.

There are currently around 37 million people living with HIV worldwide, and the only available treatment is to suppress virus — but even this treatment is only reaching 59% of the patients, and drug-resistant HIV is a growing concern. Almost one million people die annually from HIV-related causes.

“At the moment the only way to treat HIV is with medications that suppress the virus, which people need to take for their entire lives, posing a particular challenge in developing countries,” said Professor Gupta.

The study ‘HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation’ was published in Nature.

Nanoparticle HIV vaccine.

Promising new vaccine technology might finally end HIV-AIDS

A new approach seems poised to make the HIV vaccine a reality.

Nanoparticle HIV vaccine.

A model (left) of the HIV vaccine nanoparticle the team developed and its subunits (center, right).

Researchers at Scripps Research have successfully overcome past technical hurdles to creating a new HIV vaccine; the compound was shown to stimulate a powerful anti-HIV antibody response in animal models.

Enveloping attack

The team based their vaccine on a new strategy (which they describe in their paper). They drew on HIV’s envelope, Env, which is a complex, shape-shifting molecule. Env has previously thwarted vaccine-production efforts since it’s difficult to produce in vaccines in a way that induces useful immunity to HIV.

In order to stabilize Env into a shape that’s useful for the diverse strains of HIV, the team broke it down into several components. Afterward, they stitched them back together on virus-like particles (meant to mimic a whole virus). Stabilized in this fashion, the Env proteins elicited strong anti-HIV antibody responses in mice and rabbits.

“We see this new approach as a general solution to the long-standing problems of HIV vaccine design,” says principal investigator Jiang Zhu, associate professor in the Department of Integrative Structural and Computational Biology at Scripps Research.

One of the main functions of the Env molecule is to grab onto host cells and break through their membrane to initiate infection. Given its vital role, and the fact that this part of the virus has the most exposure to a host’s immune system, Env has been the main target for HIV vaccine efforts. The usual approach was to inoculate people with Env proteins (or bits of them) to coax their bodies into producing Env-binding antibodies. These antibodies would then keep HIV from infecting further cells in the future.

Up until now, that hasn’t work out. The current prevailing hypothesis is that for an HIV vaccine to be effective, it needs to present the Env proteins in a way that closely resembles the original virus. This, however, is a huge challenge. Env protrudes from the viral membrane in tight clusters of three — called trimers — which can take radically different shapes before and after infecting cells. Researchers have failed to find a broadly applicable method for stabilizing Env trimers in the pre-infection shape.

“The trimer-stabilization solutions that have been reported so far have worked for a few HIV strains but have not been generalizable,” Zhu says. “Env trimer ‘metastability’, as we call it, has really been a central problem for trimer-based HIV vaccine design.”

The team drew on Zhu’s previous work, in which he showed that altering a short section of ENV (called HR1) might force Env to stay in the pre-infection (closed) shape. The new paper shows that this strategy does indeed work for diverse HIV strains from all over the world. This “uncleaved prefusion-optimized” (UFO) approach allows researchers to produce Env trimmers in their closed shape with surprising ease and little need for purification starting from pretty standard cells (from a biotech manufacturing point of view). Zhu’s team reports successfully applying the UFO process to “30 to 40 different HIV strains” so far. In most cases, “it has worked like a charm,” Zhu says.

The researchers further refined the vaccine by genetically linking 60 such stabilized Env trimmers to individual nanoparticles that mimic the shape of a virus. The resulting vaccine molecule cannot replicate like a real virus but looks enough like one to the immune system to coax it into action.

Lab tests on mice showed that treatment with these faux viruses led to the production of antibodies that successfully neutralized HIV in only eight weeks. Even better, the HIV strain used to confirm the vaccine’s effectiveness was of a type that prior candidate vaccines generally have failed against.

“This is the first time any candidate HIV vaccine has induced this desired type of antibody response in mice,” Zhu says. Similarly unprecedented results were obtained in rabbits, demonstrating that the nanoparticle-based approach is clearly superior to the use of isolated Env proteins — it elicits a significantly stronger response and does so much more quickly.

Further tests are now underway in 24 monkeys at the National Institutes of Health-sponsored Southwest National Primate Center in San Antonio, Texas.

“We’re now testing two candidate vaccines based on Env trimers from different HIV strains, plus a third candidate vaccine that is a cocktail of three Env-based vaccines,” says Ji Li, CEO of Ufovax, a startup company that has licensed Zhu’s vaccine technology. “We think this new approach represents a true breakthrough after 30 years of HIV vaccine research.”

The paper “HIV-1 vaccine design through minimizing envelope metastability” has been published in the journal Science Advances.

Rice paddy.

GMO rice may hold the key to fighting HIV on the cheap

How’s that for internal conflict, eh, soccer moms?

Rice paddy.

A rice paddy in the Kerala province, India.
Image credits muffinn / Flickr.

An international team of researchers, with members from Spain, the U.S., and the U.K., plans to fight HIV using only cereal; namely, rice. In a new paper, they describe how they developed a strain of the plant that produces HIV-neutralizing proteins, and how the resulting rice can be used to prevent the spread of this disease.

Rice 2.0

“Our paper provides an approach for the durable deployment of anti-HIV agents in the developing world,” the team writes.

HIV isn’t the death sentence it used to be. Researchers and doctors have had quite a lot of success in developing treatments for people infected with HIV and — at least in more developed countries — death rates associated with HIV have declined significantly. The real prize is to develop a functional vaccine against the virus, an endeavor which has so far borne no fruit.

Still, since we don’t yet have such a vaccine ready, oral medication has been developed that can keep an infection at bay for a limited amount of time. However, such treatments are still expensive — prohibitively so for the many areas in third world countries that are struggling under high rates of HIV infection. Compounding the problem is that production of such drugs — involving a process known as recombinant protein manufacturing — is technologically-intensive and time-consuming, meaning that any production facilities these countries could put together wouldn’t come anywhere near to satisfying demand.

Here’s where the rice comes in. The strain engineered by the team synthesizes the same HIV-neutralizing compounds used in oral medication. Once the crop is fully grown, farmers can process the grains to make a topical cream and apply it to their skin — allowing these active compounds to enter the body. The rice plants produce one type of (monoclonal) antibody and two kinds of proteins that bind directly to the HIV virus (the lectins griffithsin and cyanovirin-N), preventing them from interacting with human cells.

“Simultaneous expression in the same plant allows the crude seed extract to be used directly as a topical microbicide cocktail, avoiding the costs of multiple downstream processes,” the team explains in their paper “This groundbreaking strategy is realistically the only way that microbicidal cocktails can be manufactured at a cost low enough for the developing world, where HIV prophylaxis is most in demand.”

Turning the seeds into cream is a very simple process, the team notes, allowing virtually anybody anywhere to have access to an HIV treatment option if required. It’s also virtually free once you have the rice. The team hopes that people living in areas with high rates of infection will simply grow as much of the rice as they need, potentially providing treatment for whole communities at a time.

However, there’s still work to be done before the GMO rice hits paddies around the world. The team wants to run an exhaustive battery of tests to ensure that their genetic machinations didn’t introduce genes for unknown (and potentially harmful) chemicals in the plants.

They’re also very much aware that GMOs are a subject of much debate, and their efforts might have to suffer from the controversy that has built around GM crops in recent years. There will also be regulatory hurdles to overcome in each part of the world where the rice might be grown and used.

The paper “Unexpected synergistic HIV neutralization by a triple microbicide produced in rice endosperm” has been published in the journal Proceedings of the National Academy of Sciences.

HIV sexual transmission recorded live as the virus crosses the genital mucus membrane

Credit: Pixabay.

For a long time, scientists have presumed that HIV infects hosts through sexual transmission by crossing the genital mucous membranes. However, it’s one thing theorizing a model, and another thing actually seeing the process in action. Now, for the first time, researchers in France have shown live how the virus infects immune system cells in an in-vitro model of the urethral mucosa.

Morgane Bomsel, a molecular biologist at the Institut Cochin (INSERM, CNRS, Paris Descartes University), along with colleagues, introduced an infected T cell into the urethral mucosa. The cell was tagged with a fluorescent-green protein in order to track its progress. Bomsel and colleagues then recorded how the T cell came into contact with the epithelial cell of the membrane when a virological synapse formed.

In the videos, you can see how this encounter spurs production of the infectious HIV virus, seen as green fluorescent dots. Then, like the neon green ray of a blaster gun in some B-grade SciFi movie, the virus sheds across the synapse into the mucosal epithelial cell.

This video shows a top view of an HIV-infected cell (green) in contact with the urethral epithelium and beginning to form a burst of viruses.

Once the virus crosses the epithelial layer via transcytosis, the HIV is engulfed by immune cells called macrophages. After an hour or two, once the virus has been produced and shed, the cell contact ends and the infected T cell moves on.

“Infected cells, once contacting the epithelium as if it is seating comfortably on it, start to spill a string of viruses like a gun does with bullets. After shedding a salve of fluorescent viruses on the mucosa that lasted a couple of hours, the infected cells decided to detach and turn away like a goodbye,” Bomsel told ZME Science.

This video shows a top view of an HIV-infected cell (green) in contact with the urethral epithelium and forming viruses. A virological synapse forms between them and virus is shed by the HIV-infected cell.

The French researcher confessed that it was “beautiful to see these populations of different kind of cells interacting together at the microscopic levels,” even though we’re talking about a pathogen as dangerous as HIV.

One of the most surprising findings, though, was that the infected T cells targeted epithelial cells directly above macrophages. This suggests there’s an interaction between the macrophages and the epithelium, which no one had predicted before.

This video shows an HIV-infected cell (green) that has already formed a synapse with an epithelial cell. The virus then starts to shed. When all the virus has been shed, the infected cell leaves.

The macrophages that consumed the HIV continue to produce and shed the virus for 20 days, after which the cells enter a latent, non-virus-producing state. However, the virus is still stored in macrophage reservoirs in the genital tissue. This explains why it’s so challenging to treat HIV. Antiretroviral therapies can keep the HIV reservoirs latent but interrupting therapy will cause the infection to rebound and continue spreading.

In light of these recent findings — which describe a precise mechanism of HIV entry and early establishment of HIV reservoirs in tissue macrophages — perhaps a vaccine active at the mucosa level could avoid an HIV reservoir formation if it is administered early upon infection.

“With our model and the detailed kinetic knowledge of how reservoirs are infected, new drugs that could potentially eradicate these reservoirs might now be established and tested,” said Bomsel.

The team of researchers is already working to find ways of purging the reservoir. They’re testing a “shock and kill” strategy where a macrophage-specific agonist is coupled to mucosal antibodies specific to the HIV surface. The plan is to activate the HIV reservoirs in the macrophages so these become visible to the immune system.

Scientific reference: Cell Reports, Real et al.: “Live imaging of HIV-1 transfer across T-cell virological synapse to epithelial cells that promotes stromal macrophage infection”.

A single injection protects monkey from HIV infections

A single injection of HIV-targeting antibodies protects monkeys from HIV infection for 20 weeks, a new study reports.

Image via Wikipedia.

Although there is still no definitive vaccine or cure for HIV, 30 years of research have brought us closer and closer to finally finding a way to kill out the virus. For instance, studies into immune responses have found that individuals with HIV can develop antibodies that block infection by a broad range of viral strains. These antibodies have been used to control the virus in patients who are already infected, and are also used to develop therapies that keep HIV at bay.

[panel style=”panel-default” title=”Antibodies” footer=””]Antibodies are proteins that the body produces to fight infections. Antibodies can attack substances that the body recognizes as alien, such as bacteria, viruses, and foreign substances in the blood. Typically, antibodies are produced to counteract a specific antigen. Antibodies can also be used in vaccinations.[/panel]

Now, Malcolm Martin of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, reports that monkeys can be protected from simian HIV (SHIV) infection in the long term, by a single injection of antibodies. He and his colleagues developed an injection by modifying two HIV-neutralizing antibodies, which enabled them to survive longer in the bloodstream. As a result, the cocktail was much more effective at destroying SHIV.

Researchers report that a single injection was able to prevent infection for a median time of 20 weeks. The ability to induce durable protection from HIV is an important step forward, which could, in time, be translated to humans.

Of course, 20 weeks is not an ideal period — researchers hope to develop an injection that lasts much longer — but this lays the groundwork for developing antibodies for use as an annual or biannual pre-exposure prophylactic. In the absence of an HIV vaccine, it’s pretty much the best thing we can hope for.

This is not exactly a vaccine, though it is an injection that temporarily protects against the infection.

The development couldn’t come a moment too soon. Since 1981, AIDS has killed at least 25 million people, and an estimated 18 million people are currently infected with HIV (the real figures are probably much higher than that).

It’s not the first time an HIV vaccine has been proposed. Just days ago, researchers proposed a solution which included dormant, last-ditch antibodies to develop a new type of vaccine. In another study, five patients were reportedly HIV-free after vaccine therapy. Scientists are zooming in on a solution, step by step.

The study “A single injection of crystallizable fragment domain–modified antibodies elicits durable protection from SHIV infection” has been published

Rat Hippocampus.

Dormant, berserk antibodies could hold the key for HIV vaccine

A class of antibodies known to attack the body itself could prove to be the last line of defense against threats that the immune system can’t engage.

Rat Hippocampus.

Rat hippocampus stained with NeuN antibodies (unrelated to this study, green), myelin basic protein (red), and DNA (blue).
Image credits EnCor Biotechnology Inc. via GerryShaw / Wikimedia.

In a world first, researchers from Sydney’s Garvan Institute of Medical Research report that a population of ‘bad’ antibodies — which are usually inactivated, because they tend to attack the body’s tissues and cells — form a vital last line of defense against invading microbes.

Mr. Hyde

The group of antibodies is usually seen in an inactive form in the body — which prompted most researchers to consider them a relic of our immune systems, discarded and permanently decommissioned by our bodies when they outlived their usefulness. And, at least on first glance, there seems to be a very valid reason for this: the antibodies, when active, attack the body’s own tissues and can lead to autoimmune diseases.

New research shows that the antibodies’ unbridled aggression may actually be by design. The study shows that they become active when a disease overcomes the immune system’s other defenses, or when pathogens try to imitate the body’s cells to stay safe. The antibodies also go through a rapid genetic modification process upon activation, following which they no longer threaten the body. However, they do remain very good at killing pathogens that disguise themselves to look like normal body tissue.

“We once thought that harmful antibodies were discarded by the body — like a few bad apples in the barrel — and no one had any idea that you could start with a ‘bad’ antibody and make it good,” says Professor Chris Goodnow, who lead researcher.

“From these new findings, we now know that every antibody is precious when it comes to fighting invading microbes — and this new understanding means that ‘bad’ antibodies are a valuable resource for the development of vaccines for HIV, and for other diseases that go undercover in the body.”

Certain pathogens, such as Campylobacter or HIV, have evolved to appear almost identical to the body’s cell and can thus fly under the immune system’s radar. Even if detected, these adaptations ensure the viruses are protected, because our bodies systematically avoid using antibodies that are capable of binding (i.e. attacking) its own structures.

Goodnow’s previous research aimed at understanding how our immune systems recognize these threats — some 30 years ago, his search led to a group of mysterious antibodies hidden inside silenced ‘B cells’. These are the immune cells that don’t engage pathogens directly; rather, they’re more like advanced weapon factories, producing biochemical defenses and releasing them into the bloodstream. Unlike your more run of the mill B cells, however, the group his team identified produces antibodies that can pose a danger to the body — so they’re kept on standby, in a silenced state known as ‘anergy’.

Dr. Jekyl

“The big question about these cells has been why they are there at all, and in such large numbers,” Prof Goodnow says. “Why does the body keep these cells, whose antibodies pose a genuine risk to health, instead of destroying them completely, as we once thought?”

Goodnow’s new paper reports that these cells can, in fact, be re-activated to fight off threats other B cells can’t — but only after they’ve been genetically ‘re-tooled’ for the task.

Working with a preclinical mouse model, the team showed that this group of cells starts producing antibodies when they run into pathogens that appear highly similar to the body’s own cells. Before they engage, however, they go through tiny alterations in their DNA sequence — which, in turn, alter the antibodies’ behavior. This step is crucial: the new model of antibodies no longer attacks the body, but become up to 5000 times more effective in murdering the invaders, the team reports.

In the model they tested, this antibody retooling only involved three DNA changes in the genomes of the B cells. The first change prevented the compounds from binding to the body’s own cells, while the other two were solely aimed at increasing their ability to bind to the invader.

Antibody.

Schematic of an antibody’s structure.
Image credits Mamahdi14 / Wikimedia.

In experiments carried out at the Australian Synchrotron, the team showed how these three DNA changes rearrange the structure of the antibodies (which use tip-like structures to bind to other cells or pathogens) to make them better stick to invaders. One change of note they report on is that the altered antibodies’ tips fit neatly on a nanoscale ‘dimple’ that’s present on the pathogens but not the body’s cells. Another important find is that these antibodies are actually super effective: the results, Goodnow noted, show that they “can be even better than those developed through established pathways”.

It’s important to note that, being drawn from observations on mouse models, the results may not be directly translateable to human biochemistry — although it likely is, further research will be needed before we can say for sure. Regardless, the team hopes their work will pave the way to new and improved vaccines based on these B cells — particularly against pathogens such as HIV, which the rest of the immune system can’t engage.

The paper “Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination” has been published in the journal Science.

Russia on the brink of HIV crisis as AIDS denial runs rampant through the country

Less than half of Russians with HIV are taking the necessary antiretroviral drugs, in part due to a conspiracy theory that’s running rampant through the country. Basically, many Russians refuse to believe HIV and AIDS are real, instead choosing to believe that they are a myth invented by the West.

Antiretroviral Drugs to Treat HIV Infection. Credits: NIAID.

As the world marks the World Aids Day on 1 December, many people have been fooled by a cruel conspiracy theory. HIV/AIDS denialism is the belief — thoroughly contradicted by conclusive medical and scientific evidence — that the human immunodeficiency virus (HIV) does not cause acquired immune deficiency syndrome (AIDS). The conspiracy theory comes with slight variations, with some believing that HIV doesn’t exist at all, while others claiming that HIV exists but it does nothing to cause AIDS. In South Africa especially, AIDS denialism has been prevalent, with researchers attributing over 300,000 AIDS-related deaths, along with 171,000 other HIV infections and 35,000 infant HIV infections, to the South African government’s former embrace of HIV/AIDS denialism. Now, this worrying trend is picking up steam elsewhere in the world.

In Russia, 900,000 Russians are living with HIV today, with 10 new cases emerging every hour. While globally, HIV rates have been slowly going down, in Russia (and much of Eastern Europe), they are growing alarmingly fast. National health interventions have been almost non-existent, and public awareness and support are very low, as is the national trust in doctors. Within this unfortunate social situation, a pseudoscience cult has started to emerge. People often don’t even learn about proper treatment options and sometimes refuse treatment altogether.

“It’s unacceptable in our day and age that children are dying while a range of treatment is available,” said Alexey Yakovlev, head doctor of the Botkin hospital in Saint-Petersburg, where a 10-year-old girl died in August after her religious parents repeatedly refused to treat her.

HIV cases have dropped worldwide, but in some parts of the world, things are starting to get worse. Credits: NIAID.

A positive diagnosis handled badly is how denialism most often begins. Without psychological support and often seeing the diagnosis as a “you only have a few years to live” sentence, patients often turn to alcohol and drugs — but even more often, they turn to the internet. As you’ve probably happened to see in your day to day life, the internet isn’t really a regulated space where you’re guaranteed to find accurate, scientific information. Quite the contrary: proper science and pseudoscience often emerge side by side, and sometimes, all you need to convince people on the internet is scream loud enough. So instead of reading accurate information about HIV, AIDS, and treatment options, you might read that AIDS is a divine punishment or something that derives from anal sex. You might learn that you need a silver enema or to put jade eggs in your vagina. Perhaps there’s a “miracle cure,” usually something simple like a fruit. In short, you might read all sorts of crap on the internet, and when you’re under the tremendous pressure which comes with a harsh diagnosis, you might fall for it. Things only get worse when celebrities start advocating such pseudoscience.

In Russia, one such celebrity is Olga Kovekh, a former military doctor, currently employed as a physician in a clinic in Volgograd. According to The Independent, she’s expressed doubts about the existence of pneumonia, vaccines, and even suggested that TB could be treated with proper administration of ham sandwiches. Of course, she addressed HIV too, reportedly stating that HIV drugs are poison.

“One goal of the AIDS myth is decreasing the planet’s population to two billion by establishing total control” through vaccinations, she said. Along with similar-minded people, she presents HIV as an American invention, something which only happens to “druggies” and “gays.” This only helps fuel denial. If you believe the propaganda, you’re not a druggie and you’re not gay, you might have a hard time understanding how this happened to you — and like a vicious cycle, it goes on and on.

“The biggest reason (for people becoming denialists) is lack of consultation,”said Yekaterina Zinger, director of the Svecha foundation in Saint-Petersburg.. “People don’t get enough information and begin to think that somebody is hiding something from them.”

“The temptation to believe that it’s a myth is very high,” she said, especially for heterosexual people that are not in risk groups commonly associated with HIV that “don’t understand how it happened to them”.

With proper medication, many cases of HIV infection can result in normal or almost normal life expectancy years. But without it, the disease can be indeed a sentence. Russia is one of the leaders when it comes to HIV testing, with 25 million tests administered last year. But with a shortage of available treatment, and with pseudoscience running amok, the country might be on the verge of a health crisis.

HIV budding.

Computer simulation identifies HIV Achilles Heel, offering new avenue for treatment

A team of scientists from the University of Chicago has managed to coax out the secrets of HIV budding, offering a new avenue of combating the frightful virus.

HIV budding.

HIV budding is the last step in the virus’ cycle. From here, it’s off to invade other cells.
Image credits Voth et al., 2017, PNAS / University of Chicago.

HIV seems to have a particular regard for the Trojan horse approach to warfare. The process is known as budding and helps HIV infect cells while staying undetected by the body. After infecting a cell, the virus forces it to form a membrane capsule filled with more of the virus. When full, this capsule is released through “budding” and floats away. Upon contacting another cell, the capsule is allowed through its membrane then promptly falls apart, starting the process anew.

“[Budding is] the final step of seven steps in the HIV life cycle. During budding, immature (noninfectious) HIV pushes itself out of the host CD4 cell. (Noninfectious HIV can’t infect another CD4 cell.) Once outside the CD4 cell, the new HIV releases protease, an HIV enzyme. Protease acts to break up the long protein chains that form the noninfectious virus. The smaller HIV proteins combine to form mature, infectious HIV,” according to the U.S. Department of Health and Human Services.

However, one team of scientists at the University of Chicago is determined to take this weapon away from HIV’s arsenal. Through computer modeling, they were able to clarify previously unknown details about HIV budding. The findings could help us create a novel line of medicine to fight the virus, and offers a novel avenue of viral research in the future.

To gag a virus

It’s previously been determined that a key component of the budding process is a biochemical protein complex called Gag. However, the exact details of budding, as well as the exact structure of the Gag complex have remained largely unexplained. This prevented the development of medicine that could counteract this process.

“For a while now we have had an idea of what the final assembled structure looks like, but all the details in between remained largely unknown,” said Gregory Voth, the Haig P. Papazian Distinguished Service Professor of Chemistry and corresponding author on the paper.

Efforts to get a good image of what the protein complex looks like on a molecular level have sadly been unsuccessful so far. As such, Voth’s team turned to computer modeling to simulate Gag in action, and from there infer its properties and structure.

First, they built their model using known parts of the Gag complex. They then simulated the interactions of this model and the conditions within cells, fine-tuning it to match cellular infrastructure and synthesis capability. Progressive tweaking of the model allowed them to zero in on the most likely configuration of the protein and the process it supports.

The team then ran a battery of tests at the National Institutes of Health and the Howard Hughes Medical Institute Janelia Research Campus, overseen by co-author Jennifer Lippincott-Schwartz, to validate their findings. And it worked.

The findings offer hope that a novel range of medicine can be developed to counteract budding, severely limiting HIV’s ability to spread or remain undetected by the immune system. In concert with methods of boosting white cells’ ability to fight the virus, this could finally produce an effective, sure-fire cure against HIV.

Another exciting element of this study is that the team proved computer simulation can come in and fill the gaps in our understanding of viral mechanisms. In cases where direct observation of molecular processes just doesn’t work, this study offers a powerful precedent.

“The hope is that once you have an Achilles’ heel, you can make a drug to stop Gag accumulation and hopefully arrest the virus’s progression,” Voth says. “It really demonstrates the power of modern computing for simulating viruses.”

Next, the researchers plan to look at the Gag complex in the HIV capsules after budding, he adds.

The paper, “Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane,” has been published in the journal Proceedings of the National Academy of Sciences.

Illustration of the HIV virus. Credit: Pixabay.

What’s the difference between HIV and AIDS

Most people use the terms HIV and AIDS interchangeably. Though the two are certainly connected, they mean different things.

Illustration of the HIV virus. Credit: Pixabay.

Illustration of HIV. Credit: Pixabay.

HIV is first and foremost a virus

Simply put, both HIV and AIDS are caused by the same human immunodeficiency virus but represent two different stages of the disease. Thought it might sound confusing at first, doctors, scientists, and the media use the term HIV to both describe the virus and the infection it causes. The distinction becomes clear once you understand the context the term is used in.

It’s not clear yet but the consensus seems to be that the virus appeared sometime in the late 19th or early 20th century in Western and Central Africa. The virus initially appeared in a non-human primate and was then transmitted to people after someone killed and ate the infected creature.

In the United States, AIDS was first recognized as a distinct condition in 1981 due to an increase in the incidence of rare opportunistic infections and cancers in homosexual men. There’s actually a rather freakish backstory about these early days of HIV/AIDS research. We’ve covered before the story of a Canadian flight attendant named Gaetan Dugas who for decades has been wrongly labeled as the ‘patient zero’ — the source of HIV infections in the United States. It was only recently that his name was cleared.

Typically, HIV causes flu-like symptoms two to four weeks after infection. Patients often describe the sensation as “the worst flu ever.” This short period is called the acute infection and unfortunately, many people mistake their HIV infection for the flu, making them susceptible to transmitting HIV to other persons. After the acute infection period, our immune systems temporarily bring the infection under control leading to the latency period.

During the latent period, an HIV infected person can feel no symptoms for years. Symptoms will arise once HIV infection turns into AIDS.

To diagnose HIV during the latent phase, doctors have a couple of tests at their disposal. When infected with HIV, the body produces telltale antibodies against it. Blood or saliva tests can detect these antibodies and determine whether or not a person is HIV positive. For this test to work, however, the person has to have been infected for at least a couple of weeks. If you suspect you’re infected with HIV, the wisest thing to do is to repeat the test after four weeks.

Another widely used HIV test looks for specific proteins produced by the virus called antigens. This test can accurately detect HIV mere days after infection.

HIV is transmitted through the exchange of bodily fluids.These fluids are blood, semen, pre-seminal fluids, rectal fluids, vaginal fluids, and breast milk. In the United States, HIV is spread mainly by having unprotected sex or sharing injection drug equipment, such as needles, with someone who has HIV. An infected mother can pass on the HIV infection to her child during pregnancy. Rarely, some people can become infected from a tainted blood transfusion. You can’t get HIV from skin-to-skin contact, nor is HIV spread through saliva.

AIDS is a condition

While HIV is a virus that causes an infection, acquired immune deficiency syndrome (AIDS) is a condition or syndrome caused by the HIV infection. AIDS develops after HIV does enough damage to the immune system to trigger the syndrome. AIDS is essentially the final stage of the HIV infection.

To diagnose AIDS, doctors look for certain biomarkers that signify the transition from HIV latency to AIDS. In its fight with the immune system, the virus ends up destroying immune cells called CD4 cells. Typically, a person who isn’t infected with HIV has a CD4 cell count of anywhere from 500 to 1,200. HIV patients with fewer than 200 CD4 cells are diagnosed with AIDS.

AIDS is also diagnosed indirectly when the presence of opportunistic infections is clear. These infections are diseases caused by various other viruses, fungi, or bacteria that would not normally affect a person with a healthy immune system.

Symptoms will vary from person to person because AIDS essentially means the patient has a damaged immune system that can’t fight infections well. So having AIDS makes you vulnerable to all sorts of other viruses and diseases. You can have AIDS but then easily get tuberculosis, pneumonia, certain types of cancer, and other infections. It’s these acquired diseases that eventually kill the AIDS patient, not the syndrome itself.

HIV vs AIDS at a glance

  • HIV is a virus or infection while AIDS is a condition.
  • A person could become HIV positive, but never develop symptoms.
  • You can have an HIV infection without acquiring AIDS. Thanks to modern treatments and medicine, people can live with HIV infections for years or even decades without acquiring AIDS.
  • In other words, someone with AIDS has to have the HIV virus, but someone with HIV doesn’t have to have AIDS.
  • HIV has no cure. The infection never goes away even if the patient never develops AIDS.
  • Like other viruses, HIV can be transmitted from person to person. AIDS, on the other hand, is a syndrome that is acquired only after a person gets infected with HIV.

Treatment and life expectancy

Once HIV turns into AIDS, the patient is in big trouble. Life expectancy drops significantly and the immune system is cut to shreds. Eventually, other infections or cancers kill the AIDS patient. Without treatment, a person whose infection progresses into AIDS can expect to survive no more than 3 years.

Today, however, HIV isn’t the death sentence that it used to be. Antiretroviral therapy (ART) can prevent HIV from replicating, vastly reducing the amount of virus in the body, thereby improving the resilience of the immune system. That being said, ART is not a cure for HIV but it can help patients live for many years with HIV without feeling sick. Before the introduction of ART in the mid-1990s, people with HIV could progress to AIDS in a few years. As such, ART is truly a life saver.

This therapy also reduces the risk of transmitting HIV to others. Often, doctors will recommend the partners of someone infected with HIV to take a preventive treatment called pre-exposure prophylaxis (PrEP). This treatment helps keep HIV from founding a permanent infection.

In early 2017, the FDA has approved a medication sold under the name of Truvada that can reduce the risk of HIV infection by up to 92 percent. And after decades of research and billions of dollars worth of funding, we seem to be inching in on a cure. In 2016, British researchers working at Oxford, Cambridge, Imperial College London, University College London and King’s College London claim they have developed a treatment that may have cured a 44-year-old British man of HIV. 

 

Child in South Africa becomes HIV free

In what may be a breakthrough moment in our fight with HIV, a nine-year-old infected with HIV at birth is now disease free.

HIV positive blood cell vs HIV negative blood cell: ‘clumping’ indicates a positive result. Image via Wikipedia / CSIRO.

“Curing HIV” seems like one of those overhyped clickbait titles — but this is not the case here. Today, at the 9th IAS Conference on HIV Science in Paris, researchers have reported an instance where HIV has truly been cured.

The child was diagnosed with the disease at one month of age and started an aggressive treatment at two months of age. The treatment lasted for 40 weeks. When he was nine years old, the child was tested and while HIV was present (in very low numbers), none were capable of reproducing. The child also didn’t exhibit any special genetic markers that might have helped him fend off the infection otherwise. It was the early treatment that did the job.

“Further study is needed to learn how to induce long-term HIV remission in infected babies,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). “However, this new case strengthens our hope that by treating HIV-infected children for a brief period beginning in infancy, we may be able to spare them the burden of life-long therapy and the health consequences of long-term immune activation typically associated with HIV disease.”

At the beginning of the treatment, the child had very high virus levels, which makes the achievement even more impressive. Aside from a reservoir of virus integrated into a tiny proportion of immune cells, researchers found no evidence of HIV, and even that hidden cache was harmless, unable to reproduce.

This isn’t the first time treatment administered at a very early age has proven successful. The first tantalizing case was the so-called “Mississippi Boy” who began anti-HIV treatment 30 hours after birth. After ceasing treatment, he controlled the virus for 27 months before it reappeared in his blood. Another case was described in 2015, in which the child started anti-HIV therapy at age 3 month and kept the virus under control for 11 years counting.

Still, as Fauci and his colleagues say, this is the first time antiretroviral therapy (ART) was so successful in the long run.

“To our knowledge, this is the first reported case of sustained control of HIV in a child enrolled in a randomized trial of ART interruption following treatment early in infancy,” said Avy Violari, F.C.Paed. Dr. Violari co-led the study of the case reported today as well as the CHER trial with Mark Cotton, M.Med., Ph.D. Dr. Violari is head of pediatric research at the Perinatal HIV Research Unit, part of the University of the Witwatersrand in Johannesburg. Dr. Cotton is head of the division of pediatric infectious diseases and director of the family infectious diseases clinical research unit at Stellenbosch University, South Africa.

An ongoing campaign is now assessing the hypothesis that administering ART in the earliest stages of life could keep the virus under control. By further studying this child, researchers could better understand how his immune system is keeping the virus in check and try to replicate this in further trials. An ongoing trial has already enrolled close to 400 HIV-exposed infants, 42 of whom are HIV infected, in Argentina, Brazil, Haiti, Malawi, South Africa, Uganda, the United States, Zambia, and Zimbabwe. The first of them will stop the treatment later this year, and then we will see if the immune system manages to keep the virus at bay. HIV’s stronghold is starting to shake.

The results were not peer reviewed. Materials provided by NIH/National Institute of Allergy and Infectious Diseases.