HIV drugs

HIV Drugs May Reduce Alzheimer’s Risk

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Summary: Common HIV drugs could reduce the incidence of Alzheimer’s disease (AD). Utilizing anonymized prescription data from over 225,000 individuals, the study found that HIV-positive patients taking reverse transcriptase (RT) inhibitors showed a significantly lower rate of AD compared to the general population.

This discovery builds on previous findings that Alzheimer’s-linked genes might be recombined by enzymes similar to those targeted by HIV treatments. The results could pave the way for new therapeutic strategies using existing drugs to combat the growing AD crisis.

Key Facts:

  1. The study analyzed prescription data from 225,000 individuals, revealing that HIV-positive patients over 60 taking RT inhibitors had fewer Alzheimer’s diagnoses compared to their non-HIV counterparts.
  2. RT inhibitors, initially developed for HIV, might inhibit similar enzymes in the brain, suggesting a potential mechanism for their effect on Alzheimer’s disease.
  3. The research was supported by notable foundations and the NIH, highlighting its credibility and the significant interest in translating these findings into new treatments for AD.

Source: Sanford Burnham Prebys

Alzheimer’s disease (AD) currently afflicts nearly seven million people in the U.S. With this number expected to grow to nearly 13 million by 2050, the lack of meaningful therapies represents a major unmet medical need. Scientists at Sanford Burnham Prebys have now identified promising real-world links between common HIV drugs and a reduced incidence of AD.

The study, led by Jerold Chun, M.D., Ph.D., was published in Pharmaceuticals.

This shows a person holding pills.
The brain appears to have its own RTs that are different from those in viruses, and the research team wondered if inhibiting brain RTs with HIV drugs actually helps AD patients.

Chun’s new research builds on his lab’s landmark publication in Nature in 2018 that described how somatic gene recombination in neurons can produce thousands of new gene variants within Alzheimer’s disease brains. Importantly, it also revealed for the first time how the Alzheimer’s-linked gene, APP, is recombined by using the same type of enzyme found in HIV. 

The enzyme, called reverse transcriptase (RT), copies RNA molecules and changes them into complementary DNA duplicates that can then be inserted back into DNA, producing permanent sequence changes within the cell’s DNA blueprint.

HIV and many other viruses rely on RT to hijack a host’s cells to establish a chronic infection, so drugs that block the RT enzyme’s activity have become a common part of treatment cocktails for keeping HIV at bay.

The brain appears to have its own RTs that are different from those in viruses, and the research team wondered if inhibiting brain RTs with HIV drugs actually helps AD patients.

To assess the link between real-world RT inhibitor exposure and AD in humans, the team analyzed anonymized medical records with prescription claims from more than 225,000 control and HIV-positive patients, and found that RT inhibitor exposure was associated with a statistically significant reduced incidence and prevalence of AD.

“Thus, we looked at HIV-positive individuals taking RT inhibitors and other combined antiretroviral therapies as they aged, and asked the question: How many of them got Alzheimer’s disease?” says Chun.

“And the answer is that there were many fewer than might have been expected compared to the general population.”

Of the more than 225,000 individuals with claims data in the study, just shy of 80,000 were HIV-positive individuals over the age of 60. More than 46,000 had taken RT inhibitors during a nearly three-year observation period from 2016 to 2019. The data was obtained through a collaboration with health information technology and clinical research firm IQVIA, led by Tiffany Chow, M.D.

In living persons with HIV, there were 2.46 Alzheimer’s disease diagnoses per 1,000 persons among HIV-positive individuals taking these inhibitors, versus 6.15 for the general population.

This control group was represented by more than 150,000 HIV-negative patients over the age of 60 with medical insurance claims related to treatment for the common cold.

“You cannot feasibly run a prospective clinical trial with this number of patients,” Chun adds. “This approach is a way to look at how a drug can act on a large patient population.”

Chun underscores that the drugs patients took in this retrospective study were designed to counter RT activity in HIV and likely only had a limited effect on many different possible forms of the enzyme active in the brain.

“What we’re looking at now is very crude,” says Chun. “The clear next step for our lab is to identify which versions of RTs are at work in the AD brain so that more targeted treatments can be discovered, while prospective clinical trials of currently available RT inhibitors on persons with early AD should be pursued.”

HIV Drugs Show Promise in Averting Complications from Bacterial Infections

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Study in mice finds a trigger for devastating condition, hints at possible treatment

Hundreds of rod-shaped bacteria, colorized magenta, strewn across a pink background.

Micrograph of Escherichia coli (E. coli) bacteria.

At a glance:

  • Remnant viral genes from ancestral viral infections linked to severity of bacterial infections and formation of abscesses in mice.
  • Antiviral drugs used to fight HIV were shown to prevent these dangerous complications of infection in lab experiments.
  • Insights into the mechanisms that lead to abscess formation open the door for new lines of thought about treating bacterial infections.

Bacterial infections inside the body can lead to abscesses — pockets of dead cells and debris surrounded by inflammation-fueling immune cells. In these pockets, bacteria multiply, causing more inflammation and further damage to surrounding tissues.

For reasons that remain poorly understood, in some cases the immune reaction can spread throughout the body, resulting in organ damage and life-threatening organ failure, a condition known as sepsis, estimated to affect 1.7 million people in the U.S. each year.

But how do the initial abscesses that set off this devastating immune cascade begin? And why do some escalate to sepsis?

Research published Jan. 16 in PNAS sheds new light on this question and also hints at a possible treatment.

Using animal models, Harvard Medical School investigators at Brigham and Women’s Hospital have identified one key mechanism that may be driving abcess formation in the liver that could culminate in sepsis.

The researchers caution that sepsis could be the result of multiple factors and that other mechanisms could be at play. However, they say their findings pinpoint a previously unknown trigger that could have important implications for treatment.

“Our work to understand the mechanisms of abscess formation and sepsis points to a new way of thinking about treatment and prevention of deleterious consequences following bloodstream infection,” said first author Karthik Hullahalli, an HMS graduate student in microbiology working in the lab of Matthew Waldor at Brigham and Women’s. Waldor is the HMS Edward H. Kass Professor of Medicine at Brigham and Women’s and an affiliated faculty member of the HMS Department of Microbiology.

The researchers say that if replicated in further studies, both in larger animals and then in humans, the work could pave the way to using existing drugs in a novel way to prevent some of the most devastating complications of bacterial infections.

The surprising role of dormant viral genes in igniting bacterial infections

The researchers examined the livers of mice infected with Escherichia coli, or E. coli, a common bacterium that infects many animals, including humans.

They found that abscess formation was linked to the presence and reactivation of dormant endogenous retroviruses (ERVs), genetic remnants of viruses that integrated into the genome of the mice following infections in previous generations.

The authors hypothesized that genetic material produced by the reawakened viruses stimulate inflammatory immune responses that in turn damage surrounding cells and thus drive abscess development. If so, the researchers surmised, suppressing the activity of the ERVs might prevent abscesses from forming.

A possible new use for antiviral drugs

To test this hypothesis, the researchers treated mice with a cocktail of reverse transcriptase inhibitors — antiretroviral drugs used to curb viral replication in people infected with HIV. They found that a single dose of the antiviral medication was enough to prevent abscess formation if delivered quickly after bacterial infection.

“Our findings show that drugs used to treat HIV can be used to prevent inflammatory complications of bacterial sepsis in animals,” Waldor said.

Further work is needed to understand whether and how antiretroviral drugs might prevent complications such as bacterial sepsis in different cases, the researchers said.

For example, Hullahalli noted that in mice, abscess susceptibility varies by sex and among tissues. In addition, the researchers noted that ERVs play a complex role in the life cycle of their host.

ERVs are switched on and off at different points in the course of an animal’s life. Most ERVs are usually deactivated and go into dormancy. In fact, if ERVs aren’t successfully silenced by the host immune system, they could lead to mutations that cause cancer or to immune dysregulation that causes autoimmune diseases later on. But these ERV genes are not always harmful. In some circumstances, ERVs could play a protective role in fighting infections by stimulating defensive immune responses.

“Whether these elements of the genome are beneficial or detrimental to an individual likely depends on context,” Hullahalli noted. “But the findings of this study suggest that there may be a role for the drugs that we currently think of as antivirals in treating inflammatory responses to bacterial infection.”

Swallowing A ‘Mini-Pillbox’ Could Change The Way HIV Drugs Are Delivered

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Researchers are working on a new way to deliver anti-HIV drugs. A six-pointed device (artist’s rendering, above) folds up to fit inside a capsule. One swallowed, the capsule dissolves and the device opens up and slowly dispenses the medication.

Maybe you’ve bought 7-day pill boxes, some with digital reminders, others that talk to you … not to mention apps that nag you to take your daily dose.

And still you forget your pills.

When the medication is antiretroviral therapy to treat an HIV infection, losing track of the dosing schedule is a life and death matter. These medications arrived like a medical miracle in 1996. Patients diagnosed with AIDS went from being handed a death sentence to knowing they had a chronic but treatable disease. If HIV/AIDS patients wanted a life expectancy equal to uninfected people, all they had to do was take their medicine — on schedule, every single day, no exceptions.

But people don’t comply perfectly with their medication regimens, even when the stakes are as high as with HIV. “I think lack of adherence to therapy is the Achilles heel of HIV treatment,” says Dr. Monica Gandhi, medical director of the HIV clinic at the University of California San Francisco (UCSF). Gandhi commented on, but was not involved with, a study published in today’s Nature Communications.

In the paper, researchers describe how they developed and tested what they call a “mini-pillbox,” swallowed once a week as a capsule that remains in the stomach for seven days while it releases daily doses of medications to combat HIV. The research was partly funded by the Bill & Melinda Gates Foundation, which is a funder of NPR and this blog.

The paper cited several studies showing that the average long-term adherence rate to life-saving AIDS drugs is 70 percent in both wealthy countries and the developing world. That means three out of ten HIV-infected patients regularly skip all or some of their pills.

“We can’t change the patient, but we can change the capsule,” says Dr. Giovanni Traverso, gastroenterologist at Brigham and Women’s Hospital, biomedical engineer and an author of the paper. “The more infrequent the dose, the more likely the patient is to take the medication.”

Researchers in medicine and engineering thought about shapes that could be folded and stuffed into a pill capsule. Rejecting a hexagon and other shapes, they came up with a delivery device in the shape of a six-pointed star that folds up to fit into a capsule about an inch in length and less than half an inch in diameter.

“The capsule looks like any capsule, but in the stomach the outer layer dissolves and the device inside opens up like a starfish,” says Traverso. Each arm of the star is loaded with antiretroviral drugs that slowly release over a week’s time. The device, about an inch and a half in diameter, is too large to pass through the stomach into the intestine. It releases medicine for a week before the star itself breaks down. The arms break off from the center and the segments are small enough to pass through the GI tract to be excreted.

So far, the weekly, slow-release treatment has been tested only in pigs because they have a stomach and digestive system similar to humans. The tests showed that the device worked as expected and released the proper amount of medication into the blood. “It’s likely we’ll complete human trials in 12 to 24 months. It could be available in the next few years,” says Traverso.

Seeking better ways to help patients take their medicine is a crucial field of research for HIV patients, says Gandhi. “Any development that gets patients away from daily dosing makes it easier to adhere to therapy. Once a week is better than daily. We would hope it could get down to once a month. An even better dream would be an implant under the skin that could release medications for a year.”

Taking prescribed drugs properly is important in any disease. A December 4, 2012 study in the Annals of Internal Medicine found that when patients suffering any illness in the U.S. don’t take their medications properly, they get sicker, are hospitalized more often and die sooner. Failing to take medications properly ends up costing the health-care system between $100 billion and $289 billion a year, the study found.

Poverty, war, inadequate health systems, mental illness or substance abuse can make it difficult or impossible for people to keep up their daily medication routine. But with AIDS, patients may have started taking their health for granted. The specter of inevitable death from AIDS is a 20-year-old memory. “People have lived a long time with HIV. They just don’t think it’s anything to worry about. They don’t feel symptoms of disease,” says Gandhi. “The fear factor is gone.”

For HIV/AIDS patients, near-perfect compliance can mean taking multiple drugs twice a day without missing or substantially delaying a dose more than three times in a month, according to UCSF research. The consequences for not meeting that standard are weakened immune systems for patients and the possibility that restarting the medications will result in the development of a strain of the virus that no longer responds to treatment.

If they follow their drug regimen perfectly, a patient’s viral load — the amount of HIV in their system — can be reduced to an undetectable amount. And that means they can no longer transmit the virus to others, according to the Centers for Disease Control and Prevention. But when patients fail to take their medications properly, their viral load rises and they can once again infect others.

“The reason we study adherence so avidly is that, unlike other diseases, taking HIV medications has implications for both personal health and public health,” says Gandhi. “I commend these researchers for thinking creatively.”

That creative thinking could help patients with heart disease, diabetes, cancer or any disease requiring daily medication. A similar device to help prevent malaria and containing a slow-release drug toxic to mosquitoes has already been tested in pigs, Traverso says. “And the star might some day be useful for Alzheimer’s patients, where the disease itself impacts the ability of the patient to take medication.”

‘Health worker’ fined for advising patient to swap HIV drugs for lavender & essential oils

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get-attachment (217)

‘A private ‘health worker’ has been fined by a Swiss court for telling an HIV-positive patient to ditch her treatment drugs and instead use lavender and essential oils. Heeding the advice, the woman stopped taking her medication in 2014.

The advice was given during a 2014 consultation with the man, who runs a clinic in the canton of Valais, Le Nouvelliste newspaper reported. The patient agreed to the natural ‘treatment plan’ and abandoned her prescription drugs.

“A patient had, at his request, stopped taking her anti-HIV medication after a consultation at the end of 2014,” a document outlining the charges against the man states.’

Early HIV drugs ‘may not stop virus’

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HIV can rapidly form invulnerable strongholds in the body, dashing hopes that early treatment might cure the virus, according to new research.

HIV

A baby was thought to have been cured with treatment hours after birth, but the virus emerged years later.

Monkey research, published in the journal Nature, suggests untouchable “viral reservoirs” form even before HIV can be detected in the blood.

Experts described it as a “sobering” and “striking” finding.

Reservoirs of HIV in the gut and brain tissue are the massive obstacle in the way of a cure.

Remarkable progress in developing antiretroviral drugs means HIV can be kept in check in the bloodstream and patients have a near-normal life expectancy.

But if the drugs stop, the virus will emerge from its reservoirs.

International research is focused on flushing the virus out of its reservoirs, but there had been hope that early treatment could prevent them forming in the first place.

‘Established’

In the study, rhesus monkeys were infected with the monkey equivalent of HIV – simian immunodeficiency virus (SIV).

The monkeys were then given antiretroviral drugs as early as three days or as late as two weeks after infection.

Treatment stopped after six months, but the virus re-emerged irrespective of how quickly antiretroviral treatment started.

It showed that viral reservoirs formed incredibly early in the course of the infection.

Dan Barouch, professor of medicine at Harvard Medical School, said: “Our data show that in this animal model, the viral reservoir was seeded substantially earlier after infection than was previously recognised.

“We found that the reservoir was established in tissues during the first few days of infection, before the virus was even detected in the blood.”

HIV
HIV is incredibly hard to beat

‘Rebounding’

It had been believed a baby girl born with HIV had been cured after very early treatment.

The “Mississippi baby” was given HIV drugs for the first 18 months of life, but then they were stopped.

Initially the virus did not return and there was hope she had been effectively cured.

But last week it was announced that the girl, now four years old, was no longer in remission after nearly two years off the drugs.

“The unfortunate news of the virus rebounding in this child further emphasises the need to understand the early and refractory viral reservoir that is established very quickly following HIV infection in humans,” Prof Barouch added.

Kai Deng and Robert Siliciano, of the School of Medicine at Johns Hopkins University, in Baltimore, Maryland, commented: “These data indicate that the viral reservoir could be seeded substantially earlier than previously assumed, a sobering finding that poses additional hurdles to HIV eradication efforts.

“Although early treatment may not prevent reservoir seeding, it has been consistently shown to reduce the size of the reservoir.”

They highlighted significant differences between these experiments and the human HIV infection, but concluded that the findings “suggest new approaches in addition to early treatment will be necessary to eradicate HIV infection”.