Tag Archives: HIV

1st Long-acting HIV Drug Combo

U.S. regulators have approved the first long-acting drug combo for HIV, monthly shots that can replace the daily pills now used to control infection with the AIDS virus. The approval of the two-shot combo called Cabenuva is expected to make it easier for people to stay on track with their HIV medicines and to do so with more privacy. It’s a huge change from not long ago, when patients had to take multiple pills several times a day, carefully timed around meals.

That will enhance quality of life” to need treatment just once a month, said Dr. Steven Deeks, an HIV specialist at the University of California, San Francisco, who has no ties to the drug’s makers. “People don’t want those daily reminders that they’re HIV infected.”

Cabenuva combines rilpivirine, sold as Edurant by Johnson & Johnson’s Janssen unit, and a new drug — cabotegravir, from ViiV Healthcare. They’re packaged together and given as separate shots once a month. Dosing every two months also is being tested.

The U.S. Food and Drug Administration approved Cabenuva for use in adults who have had their disease well controlled by conventional HIV medicines and who have not shown signs of viral resistance to the two drugs in Cabenuva. The agency also approved a pill version of cabotegravir to be taken with rilpivarine for a month before switching to the shots to be sure the drugs are well toleratedViiV said the shot combo would cost $5,940 for an initial, higher dose and $3,960 per month afterward. The company said that is “within the range” of what one-a-day pill combos cost now. How much a patient pays depends on insurance, income and other things. Studies found that patients greatly preferred the shots.

Even people who are taking one pill once a day just reported improvement in their quality of life to switch to an injection,” said Dr. Judith Currier, an HIV specialist at the University of California, Los Angeles. She consults for ViiV and wrote a commentary accompanying one study of the drug in the New England Journal of Medicine. Deeks said long-acting shots also give hope of reaching groups that have a hard time sticking to treatment, including people with mental illness or substance abuse problems. “There’s a great unmet need” that the shots may fill, he said.

Source: https://www.pbs.org/

COVID: the Risk of Death is 70% Higher for Male than for Female Patients

Evidence increasingly indicates that male sex is a risk factor for more severe disease and death from COVID-19. Male bias in COVID-19 mortality is observed in nearly all countries with available sex-disaggregated data, and the risk of death in males is ∼1.7 times higher than in females. Aging is strongly associated with higher risk of death in both sexes, but at all ages above 30 years, males have a significantly higher mortality risk, rendering older males the most vulnerable group. Sex differences are intertwined with differences in gender roles socially and with behavioral factors, which also influence COVID-19 incidence and outcomes. However, there are also possible biological mechanisms of male sex bias that affect the severity of COVID-19, particularly with respect to immune responses.

Sex differences beyond sex organs are present across species and extend to physiological systems, including the immune system. Infection by different pathogens results in differential immune responses and disease outcomes by sex, and although the pattern depends on age and other host factors, male sex is more often associated with lower immune responses and higher susceptibility and/or vulnerability to infections in animals. This is generally also the case in humans: Male patients have higher viral loads for hepatitis B virus (HBV) and HIV. Conversely, females generally mount a more robust immune response to vaccines, such as influenza vaccines. However, the heightened immune responses in females can also lead to detrimental immunopathology in infections.

The physiological response to virus infection is initiated when virus replication is detected by pattern recognition receptors. This leads to two antiviral programs by the infected cells.
Source: https://science.sciencemag.org/

Experimental Treatment May Have Eliminated Man’s HIV

A Brazilian man infected with the AIDS virus has shown no sign of it for more than a year since he stopped HIV medicines after an intense experimental drug therapy aimed at purging hidden, dormant virus from his body, doctors reported Tuesday. The case needs independent verification and it’s way too soon to speculate about a possible cure, scientists cautioned.

These are exciting findings but they’re very preliminary,” said Dr. Monica Gandhi, an AIDS specialist at the University of California, San Francisco (UCSF).This has happened to one person, and one person only,” and it didn’t succeed in four others given the same treatment, she said.

Another UCSF specialist, Dr. Steven Deeks, said: “This is not a cure,” just an interesting case that merits more study.

The case was described at an AIDS conference where researchers also disclosed an important prevention advance: A shot of an experimental medicine every two months worked better than daily Truvada pills to help keep uninfected gay men from catching HIV from an infected sex partner. Hundreds of thousands of people take these “pre-exposure prevention” pills now and the shot could give a new option, almost like a temporary vaccine.

If the Brazil man’s case is confirmed, it would be the first time HIV has been eliminated in an adult without a bone marrow or stem cell transplant. Independent experts want to see whether his remission lasts and for the intense drug combination that he received to undergo more testing.

I’m very moved because it’s something that millions of people want,” said the 35-year-old man, whose spoke to The Associated Press on condition that his name not be published. “It’s a gift of life, a second chance to live.

Source: https://www.nbcnews.com/

“Shock And Kill” Strategy To Eliminate HIV

When therapeutics battle HIV, they tend to miss pockets of resistance where HIV can hunker down until it stages a comeback. HIV, then, cannot be defeated until its remnants are roused to action, and its hiding places exposed and eliminated. This two-step strategy is called “shock and kill.” It sounds promising, but shock and kill hasn’t quite worked yet. It still needs the right shock.

Encouragingly, a better shock has been proposed by scientists at Sanford Burnham Prebys Medical Discovery Institute. These scientists, led by Sumit Chanda, PhD, director and professor and Nicholas Cosford, PhD, deputy director of the NCI-designated Cancer Center at Sanford Burnham Prebys and co-senior author of the study, have identified a drug that reawakens the virus without activating the immune system. That is, the drug makes it possible to save the immune system without having to destroy it.

What scientists have found with other ‘shock’ approaches is that they can be too hot and overactivate the immune system, or too cold and don’t wake up the virus,” said Chanda. “Our research identifies a drug that works in the ‘Goldilocks’ zone.”

The drug is a Smac mimetic called Ciapavir (SBI-0953294). Smac mimetics are a class of small-molecule peptidomimetics derived from a conserved binding motif of Smac (second mitochondria-derived activator of caspases), an endogenous protein inhibitor of apoptosis. Originally developed as cancer drugs, Smac mimetics are being evaluated for other purposes, such as fighting HIV.

Repurposed Smac mimetics have had modest success in reversing HIV latency. In hopes of building on this success, Chanda, Cosford, and colleagues decided to experiment with a Smac mimetic optimized to reverse HIV latency. The results of this work appeared June 23 in Cell Reports Medicine, in an article titled, “Pharmacological Activation of Non-canonical NF-κB Signaling Activates Latent HIV-1 Reservoirs In Vivo.” According to this article, Ciapavir is more efficacious as a latency-reversing agent than other drugs of its class.

Ciapavir induced activation of HIV-1 reservoirs in vivo in a bone marrow, liver, thymus (BLT) humanized mouse model without mediating systemic T cell activation,” the article’s authors wrote. “This study provides proof of concept for the in vivo efficacy and safety of Ciapavir and indicates that Smac mimetics can constitute a critical component of a safe and efficacious treatment strategy to eliminate the latent HIV-1 reservoir.”

Source: https://www.genengnews.com/

Coronavirus Uses Same Strategy As HIV To Dodge Immune Response

The novel coronavirus uses the same strategy to evade attack from the human immune system as HIV, according to a new study by Chinese scientists.

Both viruses remove marker molecules on the surface of an infected cell that are used by the immune system to identify invaders, the researchers said in a non-peer reviewed paper posted on preprint website bioRxiv.org on Sunday. They warned that this commonality could mean Sars-CoV-2, the clinical name for the virus, could be around for some time, like HIV.

Virologist Zhang Hui and a team from Sun Yat-sen University in Guangzhou also said their discovery added weight to clinical observations that the coronavirus was showing “some characteristics of viruses causing chronic infection”.

Their research involved collecting killer T cells from five patients who had recently recovered from Covid-19, the disease caused by the virus. Those immune cells are generated by people after they are infected with Sars-CoV-2 – their job is to find and destroy the virus.

The molecule is an identification tag usually present in the membrane of a healthy cell, or in sick cells infected by other coronaviruses such as severe acute respiratory syndrome, or Sars. It changes with infections, alerting the immune system whether a cell is healthy or infected by a virusHIV uses the same strategyMHC molecules are also absent in cells infected with that virusIn contrast, Sars does not make use of this function,” Zhang said.

The coronavirus removes these markers by producing a protein known as ORF8, which binds with MHC molecules, then pulls them inside the infected cell and destroys them, the researchers said. ORF8 is known to play an important role in viral replication, and most commercial test kits target this gene to detect viral loads in nose or oral swabs.

While drugs being used to treat Covid-19 patients mainly targeted enzymes or structural proteins needed for viral replication, Zhang and his team suggested compounds be developedspecifically targeting the impairment of MHC by ORF8, and therefore enhancing immune surveillance for Sars-CoV-2 infection”.

Source: https://www.scmp.com/

Will Llamas Become Coronavirus Killers ?

Antibodies from Winter, a 4-year-old llama with great eyelashes, have neutralized coronavirus and other infections in lab experiments.

Winter is a 4-year-old chocolate-colored llama with spindly legs, ever-so-slightly askew ears and envy-inducing eyelashes. Some scientists hope she might be an important figure in the fight against the novel coronavirus.

She is not a superpowered camelid. Winter was simply the lucky llama chosen by researchers in Belgium, where she lives, to participate in a series of virus studies involving both SARS and MERS. Finding that her antibodies staved off those infections, the scientists posited that those same antibodies could also neutralize the new virus that causes Covid-19. They were right, and published their results in the journal Cell.

Scientists have long turned to llamas for antibody research. In the last decade, for example, scientists have used llamas’ antibodies in H.I.V. and influenza research, finding promising therapies for both viruses.

Humans produce only one kind of antibody, made of two types of protein chains heavy and light — that together form a Y shape. Heavy-chain proteins span the entire Y, while light-chain proteins touch only the Y’s arms. Llamas, on the other hand, produce two types of antibodies. One of those antibodies is similar in size and constitution to human antibodies. But the other is much smaller; it’s only about 25 percent the size of human antibodies. The llama’s antibody still forms a Y, but its arms are much shorter because it doesn’t have any light-chain proteins. This more diminutive antibody can access tinier pockets and crevices on spike proteins — the proteins that allow viruses like the novel coronavirus to break into host cells and infect us — that human antibodies cannot. That can make it more effective in neutralizing virusesLlamas’ antibodies are also easily manipulated, said Dr. Xavier Saelens, a molecular virologist at Ghent University in Belgium and an author of the new study. They can be linked or fused with other antibodies, including human antibodies, and remain stable despite those manipulations.

Source: https://www.cell.com/
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https://www.nytimes.com/

Two New Trials of Coronavirus Treatment

Drugs used for treating arthritis are being tested as treatments for COVID-19, the disease caused by a new coronavirus, as researchers rush to find ways of helping patients and slowing the number of infectionsSanofi and Regeneron Pharmaceuticals said on Monday they began a clinical trial of their rheumatoid arthritis drug Kevzara as a coronavirus treatment, while in Spain a separate trial is studying if a combination of two drugs can slow down the spread of coronavirus among people. Enrolments for the mid-to-late stage trial of Kevzara, an immune-system modifying drug known as a monoclonal antibody, will begin immediately and test up to 400 patients, Sanofi and Regeneron said in a joint statement. Regeneron in February announced a partnership with the U.S. Department of Health and Human Services to develop a treatment for the new coronavirus, called SARS-CoV2, and said it would focus on monoclonal antibodies.

The virus that emerged in central China in December has now infected more than 179,000 people worldwide, according to the Johns Hopkins University, which is tracking these figures. Doctors have seen that many of those who become critically ill from SARS-CoV2 are experiencing a so-called cytokine storm, which happens when the immune system overreacts and attacks the body’s organs. Some researchers think drugs that can suppress the immune system, including monoclonal antibodies, might be useful for limiting this autoimmune response.

Meanwhile, Barcelona-based researchers said on Monday they would administer a drug used to treat HIV – containing darunavir and cobicistat – to a coronavirusinfected person. The patient’s close contacts would be administered hydroxychloroquine, a drug for malaria and rheumatoid conditions because laboratory experiments suggest it prevents this strain of coronavirus from reproducing. “The goal of our study is to separate the transmission chains,” Oriol Mitja, researcher at Germans Trias i Pujol Research Institute, told a news briefing. Patients with coronavirus can infect between 5% and 15% of the people they come into contact with during the 14 days after starting to show symptoms, he said. The trial’s goal is to reduce that number below 14 days and also to reduce the percentage of contacts infected and researchers plan to analyze the results in 21 days. Around 200 patients with coronavirus and 3,000 of their close contacts will take part in the trial, which has private and public funding.

Source: https://www.reuters.com/

Why Are HIV Drugs Being Used to Treat the Coronavirus?

On Tuesday, the Japanese government announced it will begin clinical trials to test treatments for the deadly new coronavirus that’s engulfed China and spread to over two dozen countries. Rather than new drugs, they’ll be studying existing medications already used to treat HIV and other viral diseases. But why exactly are researchers hopeful that these drugs can be repurposed for the new coronavirus, and how likely are they to work?

The new coronavirus, recently named SARS-CoV-2 due to its close genetic ties to the SARS coronavirus, is made out of RNA. Other RNA viruses include the ones that cause Ebola, hepatitis C, and yes, HIV/AIDS.

RNA viruses come in all shapes and sizes, and those that infect humans can do so in different ways. But many of the drugs that go after HIV and the hepatitis C virus broadly target weaknesses found in all sorts of viruses. The approved hepatitis C drug ribavirin, for instance, interferes with something called the RNA-dependent RNA polymerase, an enzyme essential for many virusesincluding coronaviruses—to produce more of themselves inside a cell. HIV drugs like lopinavir inhibit other enzymes that allow viruses to break down certain proteins, which cripples their ability to infect cells and replicate.

Broad antiviral drugs like lopinavir should be able to work against SARS-CoV-2scientists theorize. And there’s already some circumstantial evidence they do. Some of these drugs have been successfully tested out for SARS and MERS, for instance, two other nasty coronaviruses that have emerged in recent years.

In January, the Chinese government announced a trial of 41 patients in Wuhan that would use a combination therapy of lopinavir and another HIV drug, ritonavir. In February, the Chinese government also began a trial using an experimental drug that’s been tested out for Ebola, called remdesivir.

Remdesivir has already been deployed during this outbreak, with seemingly impressive results so far. Last month, the first documented U.S. patient with the virus was treated with remdesivir, following a week of worsening symptoms that had developed into full-blown pneumonia. Within a day of receiving the drug through an IV, though, the man’s symptoms started to improve, and he was eventually released from the hospital.

But one case does not a surefire treatment make. And even if remdesivir or other drugs do prove effective against SARS-CoV-2, they’ll only play a small part in stopping this current outbreak from getting worse. Most cases of COVID-19 (the official name of the disease caused by SARS-COV-2) are still mild and won’t be helped much by antiviral drugs. In terms of preventing the next pandemic, it’s more important to keep people from getting the virus at all, rather than finding drugs to treat them once they do.

Source: https://gizmodo.com/

Human Genetic Enhancement Might Soon Be Possible

The first genetically edited children were born in China in late 2018.Twins Lulu and Nana had a particular gene – known as CCR5modified during embryonic development. The aim was to make them (and their descendants) resistant to HIV. By some definitions, this would be an example of human enhancement.

Although there is still a long way to go before the technology is safe, this example has shown it’s possible to edit genes that will continue being inherited by genetic offspring for generations. However, we don’t yet know what effect these genetic changes will have on the overall health of the twins throughout life. Potential unintended changes to other genes is a grave concern which is limiting our use of gene editing technology at the moment – but this limit won’t always be present.

As we increasingly become less limited by what is scientifically achievable in the realm of gene editing for enhancement, we rely more heavily on ethical – rather than practical – limits to our actions. In fact, the case of Lulu and Nana might never have happened if both scientific and ethical limits had been more firmly established and enforced.

But in order to decide these limits, the expert community needs one important contribution: public opinion. Without the voice of the people, regulations are unlikely to be followed. In a worst-case scenario, a lack of agreed-upon regulations could mean the emergence of dangerous black markets for genetic enhancements. These come with safety and equity issues. In the meantime, experts have called for a temporary international ban on the use of gene editing technologies until a broad societal consensus has been established.

What should this broad consensus be? Current guidance in the UK is theoretically in favour of gene editing for treatment purposes in the future – if certain requirements regarding safety and the intentions of editing are met. This includes eliminating unintentional changes to other genes as a result of genetic enhancements, and that edits serve the welfare of the individuals involved. But when it comes to enhancement, ethical limits are harder to determine as people have different views on what’s best for ourselves and society.

One thing to consider with a technology like gene editing is that it affects more people than just the individual whose genes have been edited – and in some cases, those with edited genes could be unfairly better off than those who haven’t had their genes enhanced.

For example, if it were possible to enhance genes to improve facial symmetry or make a person more confident, it might mean these people are more likely to find employment in a competitive market, compared to those who haven’t had their genes edited for these characteristics. Future generations will also inherit and carry these enhancements in their DNA. In these ethical dilemmas, in order for one person to win, many people must (often unwittingly) lose.

Source: https://theconversation.com/

Alzheimer’s May Be Caused By Dental Infection

In a new study scientists reveal yet another reason to keep up on dental hygiene. Bacteria that cause a common yet largely preventable gum infection may also play a role in Alzheimer’s disease. The discovery also offers hope for a treatment that could slow neurodegeneration.

There were many clues in the [features of Alzheimer’s disease] that an infection is at work,” said Casey Lynch, an entrepreneur and co-founder of Cortexyme, a biotech company headquartered at the Verily Life Sciences campus in South San Francisco, who led the new research. “Many of the genetic risk factors for Alzheimer’s are related to immune system function,” she added, which suggests “immune system dysfunction might put people more at risk.

Alzheimer’s disease, an irreversible and progressive brain disorder that leads to memory loss and diminished thinking skills, affects at least 5 million Americans. Clumps of a brain protein known as amyloid plaques are a hallmark sign of the disease. Billions of research dollars have gone towards finding a treatment that destroys these mind-robbing masses. But there’s still no cure.

Not enough people are asking what is upstream of the plaques … and [brain] inflammation,” said Lynch, who has a background in Alzheimer’s research and was frustrated by the string of failed therapies for the disease. Nearly six years ago, Lynch received a call from Stephen Dominy, a psychiatrist at the University of California, San Francisco, who had studied the link between HIV and dementia.

I think I’ve found a bacterial cause of Alzheimer’s,” Dominy, who co-founded Cortexyme with Lynch and now serves as the company’s Chief Scientific Officer, told her. Dominy had spent about 15 years searching for infections that might lead to Alzheimer’s until evidence for a bacterium known as P. gingivalis became “undeniable,” according to Lynch. P. gingivalis causes periodontitis, an infection that destroys the gums and can lead to tooth loss.

When the team examined the brains and cerebrospinal fluid of Alzheimer’s patients, they found DNA from the bacterium. They also discovered bacterial enzymes called gingipains that destroy brain cells were present, too. And when they watched P. gingivalis infections play out in mice, it triggered neurodegeneration in the hippocampus, a brain structure central to memory. It also led to Alzheimer’s hallmark amyloid beta plaque production and inflammation, the researchers discovered.

The scientists then designed and created a new molecule that blocks the gingipain enzymes. The antibiotic reduced the amount of bacteria in infected mice and stopped the formation of amyloid beta plaques while reducing inflammation, the team reports Wednesday in the journal Science Advances.

Source: https://www.discovermagazine.com/