RISE SURVEY – Take part now!

The Kirby Institute is seeking people recently diagnosed with HIV to participate in a new research project. Your involvement will help us understand the experience of being diagnosed with HIV today and the impact it has on your life.

 WHAT IS RISE?

RISE stands for ‘Recent Diagnosis and the Impact of Support on Experiences of HIV’. RISE is exploring people’s experiences of being diagnosed with HIV and the changes in their lives following their diagnosis.
 
 WHAT IS INVOLVED? 
We just need you to simply complete an online survey twice a year. The survey includes questions about your experience of being diagnosed with HIV, and your life since then. The first survey will take about 35–45 minutes to complete. (The follow-up surveys will be shorter.)
 
If you agree to it, you can also take part in an interview which will enable you to talk in more detail about your experience.
 
 WHY JOIN THE RISE STUDY? 
The impact of HIV varies for each person regardless of gender, sexuality or cultural background. RISE will assess the role of different types of support on the health and quality-of-life of people newly diagnosed with HIV. By sharing your experience through the RISE Study you can can help influence the way support activities are offered in Australia.
 
 WHO IS ELIGIBLE? 
You can take part if you;

  • Have been diagnosed with HIV from 2016 onward?
  • Are living in Australia
  • Are aged 16 years or over

 WHAT NEXT? 
If you want to know more, please visit www.risestudy.org.au where you will find additional information about the study, or you can contact the study team to ask any questions you might have.


Thank you
The RISE Study team

How healthcare can prepare for My Health Record roll-out


Article by Proofpoint APJ vice president Tim Bentley

  • An important article when you consider whether or not to sign up for My Health Record 21 Jan 19

Australians have until January 31 to decide if they will opt out of a nationwide My Health Record initiative designed to ensure healthcare providers have instant online access to important patient information.

At the same time, cybercrime is the fastest growing crime in the world, and Australia’s healthcare sector is the continent’s biggest target according to a July report from the Australian Information Commissioner.

While Australian healthcare cybersecurity teams are in a constant fight to defend patient information from cybercriminals, there are three important steps healthcare providers can take to proactively secure their systems from online compromise.

Train healthcare staff to spot cyberattacks that target them.

Cybercriminals have shifted methods from attacking network infrastructure to attacking users directly to break into systems and access patient information.

While facilities can eliminate most legacy threats at the network perimeter, targeted attacks can circumvent the most sophisticated security software to exploit well-intentioned employees.

All it takes is one well-crafted email and a single click to lose critical patient information.

IT and senior management must work together to develop a robust cybersecurity awareness training program for every employee to undergo.

As it stands, approximately 3 in 4 (73.5%) healthcare organisations provide cybersecurity awareness training for end users, but only half of those trainings occur annually.

While this may satisfy regulatory requirements, it isn’t optimal for memory retention and doesn’t adequately keep pace with today’s rapidly evolving threat landscape.

Continuous awareness training aimed at the most targeted people within an organisation needs to be prioritised.

In addition, using real-world simulations within these trainings will also help staff members recognise attacks that they are likely to encounter across email, cloud apps, and social media.

Secure your email channel – cybercriminals’ attack vector of choice.
To address today’s attacks, healthcare organisations must practice the “ounce of prevention is worth a pound of cure” model by deploying a multi-layered approach to network defences.

Today’s fast-moving, people-centred attacks are immune to conventional signature and reputation-based defences.

In addition to firewalls and other perimeter security, a dedicated email security application must also be in place, removing employees from the equation whenever possible.

One of the most effective weapons in an attacker’s arsenal is business email compromise (BEC) or email fraud, which is the ability to disguise malicious emails, making them appear to come from a trusted source – often a CEO or CFO.

BEC uses social engineering tactics to fool victims into wiring funds, sending patient information, or divulging login credentials to someone the employee perceives is an authority figure.

Email fraud attempts are widespread in this industry and phishing attacks are at an all-time high. Healthcare employees are especially vulnerable to email-based attacks due to the high volume of personal health information they access, their frequent email communication with patients, time constraints in acute care settings, and highly publicised ransoms being paid by clinics and hospitals.

There has been a significant uptick in email fraud attacks aimed at clinical staff, business associates, and even patients – basically anyone who can access medical records.

Proofpoint’s research has shown that cybercriminals are especially targeting pharmacy directors, who control drug access, and chief nursing officers, along with any employee who can legitimately access all patient records.

These attacks are tailor-made for the recipients, often including specific references to the individual gleaned from researching their social media accounts.

This research is done with the goal of getting their attention and increasing the likelihood of ‘open rates.’

Rounding out this Pandora’s box of vulnerability is the fact that many medical facilities have complex supply chains running multiple clinical systems and security applications – many of them outdated.

One additional important component of an effective email security strategy is to deploy email authentication protocols such as DMARC and lookalike domain defences.

These technologies stop many attacks that use your trusted brand to trick employees, partners, vendors, and patients.

Our research shows that 1 in 5 emails purported to be from a healthcare organisation in 2017 was fraudulent.

Furthermore, of three billion emails using the domain of a known healthcare brand, about 8.3% of these were in fact from sources that were either unauthorised or malicious.

Deploy CASB to get visibility into the cloud apps, services, and add-ons your employees use.
You can’t defend against what you don’t know.

As more and more organisations rely on cloud-based solutions to conduct global operations, enterprise security teams must have clear visibility into the third-party applications running within their environments (Microsoft Office 365, Google G Suite, Box and others) and appropriately secure them.

Best practice calls for organisations to deploy a cloud access security broker (CASB) solution that combines user-specific risk indicators with cross-channel threat intelligence to analyse user behaviour and detect anomalies in third-party apps.

Without this, healthcare providers don’t know when users and patient data are at risk.

CASB solutions allow IT administrators to deploy tools to detect unsafe files and content, credential theft, data loss, third-party data access, and abuse by cloud scripting apps.

Healthcare cyber attacks can have serious, if not fatal consequences, and Australians are looking to trust healthcare providers with their information.

It’s essential that security teams have the proper technology to quickly remediate risk while proactively educating the healthcare workforce to detect and quarantine today’s online threats.

The Road Ahead for HIV Cure Research

Today, with better understanding of the complex task at hand, cure researchers are investigating multiple avenues and taking the long view.  This article comes from Benjamin Ryan and was first presented online in Poz.com on January 7, 2019

Cure research and the potential for a cure is still front and centre in many of our lives and this article talks about the road ahead and some of the setbacks that have been suffered along the way.


HIV cure researchers received some disappointing news at the July 2018 International AIDS Conference in Amsterdam. Two studies in particular offered a sobering lesson on how extraordinarily complex developing a safe and effective cure for the virus will likely be.

As conference attendees learned, researchers behind a randomized trial of an HIV cure method, the largest such study to date, recently found that their efforts failed to reduce viral DNA in human participants. The trial, called RIVER, tested the “kick and kill” strategy that seeks to roust latently infected immune cells from their slumber and then kill them off. Standard HIV medications—antiretrovirals, or ARVs—work only against cells that harbor actively replicating virus. These resting infected cells are a chief component of what is known as the viral reservoir, and it’s the stubborn persistence of this reservoir that frustrates cure efforts.

In a second study presented at the conference, an antibody treatment that had shown promise in monkeys failed to prompt what is known as posttreatment control of the virus after HIV-positive humans interrupted their ARV therapy.

As scientists in this field recalibrate their expectations, the use of the term “cure” as a goal for their research is declining. Instead, investigators may seek to induce posttreatment control of HIV, or viral remission, in which a particular therapy would not eradicate the virus from the body but rather suppress HIV over an extended period without the need for long-term ARV treatment.

Nevertheless, the overall field is generally still referred to as HIV cure research.

Taking the pulse of her fellow HIV cure researchers, Sharon R. Lewin, MD, PhD, director of The Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia, says, “If anything, there was probably more optimism four years ago because we had tried fewer things. We now know that curing HIV is definitely not an easy task.”

Looking on the bright side, Lewin points to other promising recent cure studies conducted in primates, noting, “We definitely have been able to cure a few monkeys. That’s exciting.”

But as the antibody study presented at the Amsterdam conference indicated, disappointing outcomes among humans might follow success in primate research.

“The preclinical studies have universally shown more favorable outcomes than human studies,” says Jintanat Ananworanich, MD, PhD, who in her capacity as the associate director for therapeutics research at the U.S. Military HIV Research Program directs research in the HIV cure field. “Although no strategies have resulted in remission in clinical trials thus far, tremendous knowledge on HIV persistence and immune responses has been generated. This is important to informing future trials.”

Concerns about recent setbacks notwithstanding, Lewin remains optimistic about the future of HIV cure research. “Science can also take dramatic turns with significant discoveries too,” she says. “So you never know what may change the field dramatically.”

Lewin is the lead author of a literature review recently published in The Lancet HIV, “Barriers and Strategies to Achieve a Cure for HIV,” in which she and her three coauthors offer a comprehensive summary of the impressive number of avenues researchers are pursuing in their quest for a cure, or something close to it. Below, POZ looks at the main takeaways from their paper. We also explore a few HIV cure studies published more recently.

***

Lewin and her colleagues note that the only person ever cured of HIV remains Timothy Ray Brown. As a component of his treatment for leukemia, Brown received stem cell transplants a decade ago from a donor with a genetic mutation that confers natural resistance to the virus—the surface of the donor’s immune cells lacked the CCR5 coreceptor to which most HIV attaches in order to infect the cells. As far as researchers can tell, Brown benefited from a sterilizing cure. There is no evidence in his body of any virus with the capacity to replicate, and his viral load has never rebounded. (Today, Brown actually takes Truvada [tenofovir disoproxil fumarate/emtricitabine] as pre-exposure prophylaxis [PrEP] to ensure he does not contract HIV again.)

Otherwise, in the realm of posttreatment control of HIV, quite a few people with the virus have been able to suppress their viral load for long stretches, sometimes for years, after interrupting standard ARV treatment. A recently published paper found that those who began ARVs very soon after contracting the virus are more likely to achieve such a prolonged state of viral remission after eventually going off their meds. It is likely that beginning on ARVs so promptly after infection keeps the viral reservoir relatively small, thus reducing the likelihood of latently infected cells springing to life at any given moment following a treatment interruption.

One of the most famous cases of such posttreatment control is that of the African child who was treated for HIV for less than a year after birth and, by the time the child’s case was reported in 2017, had spent over eight years in a state of viral remission. In 2015, news surfaced that an 18-year-old French individual had spent 12 years off ARVs and still controlled the virus. Then, of course, there was the 2013 case of “the Mississippi Child”—met with great fanfare—who spent a couple of years off ARVs during her very young life but ultimately, and disappointingly, experienced a viral rebound at 4 years old.

According to Lewin, scientists’ increasingly enriched comprehension of the posttreatment-control phenomenon has actually made designing HIV cure studies more difficult. Now researchers must take into account that some study participants might achieve control of their virus, even if for a short time, without the benefit of an investigative cure therapy, thus making it more challenging to prove that a cure treatment was the cause of viral remission or a delayed viral rebound after the interruption of ARV treatment.

***

Not only do latently infected immune cells evade ARV treatment, but also for every million such cells, perhaps only 60 harbor virus that can actually replicate; the rest contain defective virus. So finding those resting cells capable of waking up and repopulating the body with new virus in the absence of ARV treatment can be akin to finding a needle in a haystack. The immune system itself wastes considerable energy going after cells infected with dud copies of the virus.

In another of the myriad ways HIV has evolved to help ensure it sustains a lifelong infection, latently infected cells have the ability to clone themselves. Perhaps more than half of the viral reservoir cells in some people living with the virus are clones.

The matter of whether HIV continues to replicate at low levels in the face of effective ARV treatment has been the source of significant controversy in the cure field. A study presented at the 2018 Conference on Retroviruses and Opportunistic Infections in Boston found no evidence of such ongoing replication in the lymph nodes, calling into question the notable contrasting findings of a 2016 paper.

***

The lack of precise tests for measuring the viral reservoir remains a considerable obstacle for HIV researchers, both in determining the challenge they face in their quest to vanquish an infection and in assessing how well they did. Currently, scientists in the field must rely on rather crude metrics, such as changes in the overall presence of viral DNA or RNA in the blood, to gauge how a particular treatment affects the size of the reservoir. (HIV carries its genetic code in RNA, which is copied to DNA during infection of a cell.) Such metrics can underestimate the population of infected cells because most virus hides in tissues, not blood.

Scientists may also try to measure success by determining whether an HIV cure treatment is associated with a delay in viral rebound after an interruption of ARV therapy and whether such a treatment is associated with a particular level of control of the virus in the absence of standard ARV therapy for the virus.

If only scientists could identify a specific biomarker, such as a particular protein, that could predict the likelihood of a delay to viral rebound or control of the virus after a treatment interruption. Then, study participants might be spared the burden of interrupting their ARVs, a common requirement in HIV cure study designs. Asking people to stop standard HIV treatment raises ethical questions and may discourage people living with the virus from entering cure trials. That said, multiple studies have indicated that treatment interruptions in cure studies are safe.

Lewin argues that such a tidy biomarker would likely attract greater investment in the field from pharmaceutical companies. (Global funding for public sector HIV cure research increased from $88 million in 2012 to $289 million in 2017, with the lion’s share coming from the National Institutes of Health.) Such for-profit companies prefer study designs boasting a level of simplicity that will help an investigational treatment pass muster with regulatory bodies like the Food and Drug Administration. They also prefer efficient investments for their research and development dollars. So their researchers favor clearly delineated, objective means of measuring success in clinical trials of experimental agents.

Case in point: The recent discovery of a biomarker that can predict whether an individual will achieve a functional cure of hepatitis B virus (HBV) gave rise to a surge of interest from the pharmaceutical industry in researching curative therapies for HBV.

Investment in Cure Research chart

Source: “Global Investment in HIV Cure Research and Development in 2017”

Investment in Cure Research chart

Source: “Global Investment in HIV Cure Research and Development in 2017”

Avenues of Research:

Stem cell transplants

Clinicians are still trying to replicate the success of Timothy Brown’s HIV cure with similar strategies. In recent years, a number of other individuals with cancer have received stem cell transplants from donors who also have the genetic mutation related to the CCR5 coreceptor that confers resistance to the virus. One of the six such individuals whose cases have been published in scientific literature experienced a viral rebound; the other five ultimately died as a result of complications following their stem cell transplant or from their underlying cancer.

In other cases of people living with HIV who received a stem cell transplant but from a donor who lacked the CCR5-related genetic mutation, the stem cell transplant did delay the time to viral rebound by 3 to 10 months after the individuals stopped ARVs.

However, the high fatality rate following transplantation highlights how impractical, not to mention unethical, this method of attempting to cure HIV is for anyone not already facing a high risk of death due to cancer.

Gene therapy

Seeking safer alternatives to cancer-treatment-based stem cell transplants, researchers are experimenting with gene-editing techniques that alter the DNA of an individual’s immune cells. In particular, the scientists will try to deactivate the gene that gives rise to the CCR5 coreceptor, thus robbing HIV of a means of latching onto immune cells. The modified cells are then grown outside the body and ultimately reinfused into the person’s body. The aim is to spawn a population of immune cells that are resistant to infection. As the field of gene editing rapidly evolves, it is hoped that new, even more cutting-edge technology will facilitate progress on the HIV cure front.

“Kick and kill”

The method of waking up latently infected cells (the “kick” part) and then finishing them off (the “kill” part) has yielded some notably disappointing results of late, including those of the RIVER study that was presented at the July conference in Amsterdam. Researchers pursuing this strategy have looked to various cancer drugs known as HDAC inhibitors as the kick element; but thus far, they have not been able to show such drugs can actually diminish reservoir cells.

Lewin remains cautiously optimistic about further research into these medications, noting that the RIVER trial used a less advanced and relatively weak kick agent. Recent, more preliminary studies that have examined other kick agents, such as so-called TLR agonists, have shown far greater promise.

On this front, Gilead Sciences is investigating a drug known as GS-9620 that has shown positive results in primate research.

Latency silencing: “block and lock”

Effectively the opposite of the kick and kill strategy, the “block and lock” method, also known as latency silencing, is based on the presumption that if rooting out and killing all the latently infected cells in the body is too challenging, keeping them in a silent state indefinitely may be a viable alternative. A recent study conducted in mice sought to inhibit a viral protein known as tat that acts as an on-off switch for viral replication in cells. The study successfully reduced the amount of HIV RNA expressed in tissue biopsies taken from the animals, and it delayed viral rebound after the interruption of ARV treatment.

Enhancing the immune system

Researchers are investigating whether vaccines can be used to prompt the body to better control the virus.

Scientists have also invested considerable energy into studying so-called broadly neutralizing antibodies, which are natural antibodies that boast the capacity to combat a wide array of HIV strains. Research has indicated that some of these antibodies are associated with a delay in viral rebound after an ARV treatment interruption. Recently, scientists have gone high-tech by synthesizing three such antibodies into one “trispecific” antibody—a kind of all-in-one triple combination therapy—that has already shown promise in its use as pre-exposure prophylaxis (PrEP) among primates.

Modulating the immune system

Scientists are seeking to manipulate proteins that redirect the traffic of immune-fighting cells. One such example is an antibody called vedolizumab that targets a protein on the surface of CD4 cells and stops these cells from moving into the gut, where HIV focuses much of its assault on the immune system. An initial study in monkeys reported two years ago provided hope for progress in this area of research, but scientists recently repeated the study and found that the antibody had a null impact on the second go-round. Preliminary results in humans also showed that vedolizumab did not affect the time to viral rebound after individuals interrupted their ARV treatment.

Looking to the future

In all likelihood, a successful HIV cure, or posttreatment control, strategy will rely upon a combination approach based on a number of the methods currently under investigation or those yet to be imagined.

“It is clear that achieving HIV remission will not be easy and that one should not expect any single intervention to help people get to remission,” says Jintanat Ananworanich. “We are taking small steps in discovery science.”

Any successful method will need to be safe, effective and—if it is to make a significant dent in the global epidemic—scalable. An HIV cure therapy that is extraordinarily expensive thanks to, for example, the highly involved and complex process required to provide personally tailored genetic editing of an individual’s immune cells, will have little to offer poorer nations—in particular those in sub-Saharan Africa—where the need is greatest.

Curative hepatitis C virus (HCV) treatment, for example, costs tens of thousands of dollars in the United States, which has led insurers to restrict coverage of the medications. The actual cost to manufacture such medications, however, is relatively low, which allows for a steep sliding scale elsewhere around the world.

The future of HIV cure science is also up against the phenomenal success of ARV treatment, which has set a high bar for any alternative means of suppressing the virus. The life expectancy of those on ARVs is approaching normal. What’s more, the risk of transmitting HIV is effectively zero for those who maintain a fully suppressed viral load.

However, such benefits don’t speak to the psychic costs of living with a highly stigmatized lifelong infection or how a cure therapy may alleviate such burdens. Then there are the extreme difficulty and expense of getting the global population on lifelong ARV treatment. Also, even well-treated HIV is associated with an increased risk of numerous health conditions, such as cardiovascular disease and cognitive decline.

Some form of HIV cure could help address these problems. However, as HIV drug development continues to progress and long-acting injectable treatments, or even very long-lasting implants, become the standard of care, emerging HIV cure treatments may cease to offer the freedom from daily medications as an advantage over standard ARV therapy. (Or perhaps by then, long-acting antibody treatments will be the norm.)

Furthermore, if someone is in a state of posttreatment control of the virus, what reassurances will there be that the virus will remain dormant indefinitely and won’t suddenly surge back and make an individual unwittingly infectious? How frequently will people benefiting from viral remission need viral load monitoring?

These pressing questions, along with HIV’s extraordinary complexity, likely make for a long and winding scientific road ahead. But thanks to the increasing funds backing such research and a growing army of top-tier scientists doggedly pursuing a cure, the future will hopefully prove bright with new developments.

Still, this field isn’t simply concerned with a binary outcome of finding the holy grail of a cure or otherwise failing to do so. Success will likely prove incremental, with scientists eventually discovering new means of further mitigating HIV’s long-term harms, further transforming a once surely fatal infection into an increasingly innocuous presence in the body and around the world.

 

Even When Well Treated, HIV Is Linked to Advanced Aging

Researchers analyzed 10 biomarkers associated with biological aging among a group of HIV-positive and -negative Europeans.

This article is a reprint from POZ.com  from January 17, 2019  By Benjamin Ryan

Publishing their findings in the journal AIDS, researchers from the ComorBidity in Relation to AIDS (COBRA) study analyzed 134 people with HIV and 79 HIV-negative people with similar sociodemographic and lifestyle factors. The participants were recruited in Amsterdam (these were at least 45 years old) and London (these were at least 50 years old).

All the HIV-positive individuals were on antiretrovirals and had had a fully suppressed viral load for at least 12 months.

The researchers also studied samples from 35 blood donors selected from the Dutch national blood bank in Amsterdam. They were matched with the HIV-positive and -negative individuals from the COBRA study according to age and had all tested negative for HIV, hepatitis B and C viruses (HBV/HCV), syphilis and human T-lymphotropic virus 1 and 2 (HTLV).

The investigators tested the participants for 10 biomarkers that previous research has indicated are associated with biological, as opposed to chronological, aging.

Among the COBRA study members, biological age was greater than chronological age by an average of 13.2 years among those with HIV and 5.5 years among those without the virus. For the blood donors, biological age was an average of 7.0 years lower than chronological age.

After adjusting the data for various factors, including HIV status, the study authors found that the following factors were significantly associated with a greater average biological age compared with chronological age: chronic HBV, 10.05 years; total anti-cytomegalovirus (CMV) IgG antibody levels, 1.83 years per 10-fold increase; and CD8 cell count, 0.44 years per 100-cell increase.

After adjusting for chronic HBV infection status, total anti-CMV IgG antibody levels and CD8 levels, the analysis indicated that the HIV-positive COBRA participants had a greater discrepancy between biological and chronological age compared with their HIV-negative counterparts (4.5 years on average) and with the blood donors (19.0 years on average).

After conducting another analysis in which they adjusted the data for various factors, the study authors found that HIV-related factors associated with a greater biological age compared with chronological age included: cumulative exposure to the antiretroviral Invirase (saquinavir), 1.17 years per year of exposure; a lowest-ever (nadir) CD4 count of less than 300, 3.0 years; chronic HBV, 7.35 years; and total anti-CMV IgG antibody level, 1.86 years per 10-fold increase.