Category: Research

The Future of HIV: Novel Treatment Options & A Possible Cure

by pragmaticsolidarity, posted in APHA IH Section, Health Equity, HIV/AIDS, Infectious Disease, Pharmaceuticals, Research

As the medical community and those it serves welcomed in a new year, it brought with it the hope of scientific advancements that will alter the course of certain disease states. These advancements include the use of stem cells to treat to treat macular degeneration, novel microscopic techniques to capture images of the brain, the continued observed effectiveness of the experimental Ebola vaccine, and countless other interventions aimed at creating a healthier global society. Included in these optimisms for 2019 is the possibility for novel treatment options and a possible cure for one of the world’s leading causes of death, HIV. The stories of Timothy Brown – the only individual ever to be cured of HIV, the Mississippi baby and Clark Hawley – both having an extended period of time with undetectable HIV viral load with an interruption of Antiretroviral Therapy (ART), and the Boston patients/Mayo Clinic patient – all three having undetectable HIV viral loads for an extended period of time after a stem cell transplant, have brought much sanguinity to health care professionals and patients alike. However, these exciting results have been unable to be replicated in the majority of the population suffering from HIV and remain unique in their respective occurrences. Although ART has been vital to the HIV community in terms of longevity and quality life, there are still certain populations that are seeking other mechanisms to treat this infectious disease – and, of course, always coveting the idea of a cure. The following is a brief glimpse at the vast pipeline that awaits 2019 and the anticipations of the global healthcare community.  

Combination Approaches

  1. The AIDS Clinical Trial Group (ACTG) is currently exploring the option of combining vorinostat, a HDAC inhibitor along with tamoxifen, which is an FDA approved medication the treatment of breast cancer for postmenopausal women. Utilizing this approach is thought to prevent the reactivation of HIV in CD4+ cells that are latent in addition to increasing the latency-reversal effect of vorinostat through tamoxifen.
  2. Researchers from the USA, France, Germany, Italy, Spain, Switzerland, and the UK are collaborating for a trial testing the combination of two HIV vaccine candidates alongside a monoclonal antibody called vedolizumab. This method of treatment is thought to target a certain protein in the body, α4β7 integrin, that plays a role in transmission of HIV into CD4+ cells. In a macaque model, this combination has shown the control of SIV (HIV but in simians) after discontinuing ART.
  3. At the University of Minnesota, researchers are testing infusions of natural killer (NK) cells with the administration of cytokine interleukin-2 (IL-2). The researchers are hoping to add to the evidence of NK cells being able to exhaust HIV reservoirs and to control virus replication.
  4. In a version of the “kick & kill” method of curing HIV, researchers in Oxford and Barcelona are using a medication to active the latent HIV reservoir while boosting the immune response 1000 times stronger than the usual to rid the body of the virus. Preliminary results showed that 5/15 patients had undetectable viral loads for seven months without ART.

Immunotherapy Approaches

  1. Immunocore, a company founded in Oxford with heavy investment by Bill Gates, has designed T cell receptors that seek out and bind with the HIV virus. These receptors then instruct immune T cells to eliminate any HIV-infected cells, even when the levels happen to be extremely low. Since levels can be rather low in the reservoir of HIV virus that exists in an infected individual, this is a promising lead to completely remove this retrovirus from the body. This immunotherapy has shown to be effective in human tissue samples, but no results being tested in humans have been released.
  2. In France, a company known as InnaVirVax has established a vaccine, VAC-3S, that allows the body to stimulate a production of antibodies against the HIV protein 3S. This, in turn, causes T cells to attack the virus. This is considered a novel approach because it encourages the immune system to recover while equipping it with the tools to continue fighting off the virus. VAC-3S has completed Phase 2a trials, and is partnered with a DNA-based vaccine from FIT Biotech, a Finnish company, that both parties believe can lead to a functional cure.  
  3. In a recently initiated trial, IMPAACT 2008, held in the USA, Botswana, Brazil, and Zimbabwe, a broadly neutralizing antibody termed VRC01 is being investigated for its effectiveness in infants with HIV who are also started on ART within 12 weeks of birth. Although the study aims at establishing the safety profile for VRC01, it is also observing the difference in the HIV reservoir compared with only ART.

Novel Antiretroviral Agents

  1. The manufacturer, ABIVAX, believes it has developed a compound that may help the immune system recognize cells infected with HIV by allowing an increased presentation of HIV antigens on the cell’s service. This would lead to an augmented immune response to abolish these infected cells. This compound has been labelled ABX464 and targets the HIV protein Rev, which is responsible for the transcription of HIV RNA. Reductions of measured HIV DNA have been reported from 25% to 50% in eight of the fifteen patients participating in the study; however, no delay in viral load rebound was found when compared with placebo.
  2. Gilead has created a novel mechanism of targeting the HIV virus through the capsid inhibitors class. Capsids are involved in protecting HIV RNA and related proteins, and capsids also breaks down to release the viral contents into CD4 cells which enable reverse transcription to take place. The novel agent by Gilead, GS-CA1, blocks both the assembly and disassembly of capsids that create non-infectious and defective viruses.

Gene Therapy

  1. Chimeric antigen receptor (CAR) T therapy has been re-initiated in the first cure related clinical trial of this approach in people living with HIV who are on ART. CAR T cell therapy involves the modification of an individual’s T cells that can target antigens of interest. The specific cells modified by the initiative in China, called VC-CAR-T cells, have been modified to target HIV gp120. These modified cells were able to induce the destruction of HIV-infected cells, including latently infected cells exposed to latency-reversing agents, in the laboratory setting.  
  2. With the knowledge of knowing that about 1% of the world’s population is immune to HIV due to a genetic mutation on the gene that encodes for CCR5, US-based Sangamo has begun to edit DNA to introduce the aforementioned mutation. The CCR5 protein is attached to the surface of CD4 cells that allows HIV to enter and infect the cell; with the mutation, it would be impossible for HIV to enter cells. This company extracts patient’s CD4 cells in order to use zinc finger nucleases to edit patient’s DNA to make them resistant to HIV.
  3. Although a highly controversial topic amid the recent publication of the use of CRISPER in twin daughters in China, scientists believe that this tool can lead to a cure for HIV as it is believed to be a much easier, faster, and effective approach than other gene-editing methods. However, the majority of the global health community is in agreement that years of laboratory research and ethical standards need to be established before human trials are properly started.

With the HIV virus adapting and mutating to evade treatments almost as rapidly as the world is producing novel approaches to treating this infectious disease, the drive for continued research and testing should be relentless. These aforementioned examples of novel treatments and possible cures display the creative and diverse thought processes the medical community has put forth to tackle one of the most stigmatized diseases on this earth. However, the ethics behind these trials need to be sound and forthcoming for all of humanity. The trials that occur need to ensure an assortment of demographics including individuals from both developed and developing nations – a subtle form of medical colonialism has no place in the global health community. In addition, trials that enroll patients who willingly accept the benefits and risks associated with the experimental therapy have the moral obligation to supply lifetime treatment if it happens to be effective. The researchers and medical professionals who monitor these participants need to take extreme caution in ART interruptions/discontinuations and certify that the patients realize what complications could transpire due to them. Finally, and most importantly, the interventions that show promise of novel ways to approach HIV or even a cure have to be accessible, affordable, and available to all humans who suffer from HIV. The health inequalities that plague this fragile planet have already been clearly highlighted in this ailment throughout history; the global health community is in debt to humanity for a cure for all when discovered.  

With the global health community’s commitment, the future of the HIV virus continues to transition from infectious disease to chronic disease. While the step that will advance the chronic disease to a cure is still thought to be unknown, the excitement behind the aforementioned gene editing therapy is substantial. The ability to safely, effectively and ethically modify human cells to prevent the entry of the virus into the immune system is certainly the most promising option recently and possibly from this disease’s initial appearance; although, health care professionals haven’t quite figured out how to combine these aspects yet. A cure or even functional cure may be years away, but the global health community needs to continue to accompany those inflicted by this chronic infectious disease to meet the hopes and expectations of alleviating the burdens of HIV.

An “epidemic of poor quality”: New study finds that poor healthcare quality leads to millions of deaths globally

by Yara Asi, posted in APHA IH Section, Health Systems, MDGs / SDGs, Policy and Advocacy, Research

This is part 1 of a 4-part series on global healthcare quality.

The Sustainable Development Goals (SDGs), the global effort led by the United Nations to prioritize and standardize development goals in every country for the period 2015-2030, offer ambitious targets when it comes to the world’s health. SDG 3 is focused entirely on outcomes of health and well-being, such as reducing maternal mortality, ending diseases like AIDS and malaria, achieving universal health coverage (UHC), and ensuring universal access to reproductive health care. Other SDGs, such as Goal 2 which calls for zero hunger and Goal 6 that aims for universal and equitable access to safe drinking water as well as equal and adequate access to sanitation, have obvious implications for health. However, a recent Lancet Global Health Commission, chaired by Associate Professor of Global Health Dr. Margaret Kruk of the Harvard T.H. Chan School of Public Health, has come to some surprising conclusions about health systems in low- and middle-income countries (LMICs). Despite a push in humanitarian advocacy and research to focus on increasing healthcare access in LMIC, it is the quality of healthcare that is received by patients in these environments that may require more of our attention. The Commission estimates that as many as 5 million die each year because they are receiving poor-quality healthcare- more than a million more people than those who die due to no access to care at all (3.6 million). That means that annually, 8.6 million people living in LMIC are dying due to poor-quality healthcare systems. Poor quality care can be dangerous for patients, provides misleading data points about healthcare system improvements, and may support corrupt and fraudulent behavior by parties with power in the health sector. Is it possible to achieve the SDGs in this environment?

Health systems should be judged on “what they do for people- not how many doctors they train.”

Dr. Kruk describes quality healthcare systems as based on three factors: effective care, trust of the people, and a system that is able to adapt, both in cases of acute emergencies and with a longer-term vision. While many advancements in access can be supported by metrics, it is possible that we haven’t been measuring some of the factors that really matter. Dr. Kruk told NPR that health systems should be judged on “what they do for people- not how many doctors they train.” The Commission’s study, which was published by the Lancet earlier this month, found that the millions of deaths each year that can be attributed to poor health systems included many deaths due to factors the SDGs explicitly seek to reduce, such as neonatal conditions and traffic accidents. While one of the central tenets of SDG 3 is UHC, the Commission argues that the quality of care “is not yet sufficiently recognized in the global discourse on UHC” and that countries undertaking policies that bring them to UHC “must put better quality on par with expanded coverage” to improve health. The Commission identifies several individual initiatives in LMIC that are developing mechanisms for quality measurement and improvement. However, it is clear that improving the quality of care has not received the effort that expanding access to care has achieved, which will undoubtedly undermine efforts to achieve the SDGs, even if UHC is attained. While expanding access to care must remain a global priority, we cannot discount the need to ensure that care given is of high quality as well. Several studies from LMIC during the period of the Millennium Development Goals (2000-2015) suggested that in some instances, expanding access to care did not lead to more positive health outcomes because the quality of the care received was poor. However, we still do not even have highly rigorous and consistent tools with which to measure healthcare quality across global contexts in a way that would allow for standardized measures and generalizable conclusions.

Aside from the historical focus on access to care by humanitarian and governmental actors, there a few other reasons that quality of care has not received the appropriate amount of attention of donors and policymakers. Healthcare systems in LMIC are generally disintegrated, with pockets of government services, humanitarian agencies, and private facilities operating throughout the country. This complexity allows for the intrusion of many political and logistical barriers to providing high quality care consistently. In the public sector, corrupt bureaucrats may opt to control who is able to receive jobs at healthcare facilities rather than allow for a merit-based system where poorly qualified staff could be replaced by qualified employees, regardless of political factors. For-profit providers who have disparate financial interests may not properly follow treatment or diagnosis guidelines that are critical to quality care. However, entirely closing low quality facilities would leave some citizens with no access to care at all.

Dr. Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization, published a response to the Lancet Commission, agreeing that “nothing less than a revolution” is needed to ensure that high quality care is delivered in every health system around the world, an essential component of SDG 3. He posits that poor data is one of the largest barriers to improving healthcare quality, arguing that we must “go beyond counting simply what services are delivered to measuring how they are delivered.” He calls for a “global learning laboratory for quality,” where local lessons based on the “messy realities of health services” are prioritized, but where these lessons are then disseminated and can be implemented, measured, and compared in contexts around the world. Policymakers and practitioners working in LMIC must consider these factors when designing and implementing health services or research studies. The Lancet Commission points to five distinct foundations where learning and improvement in the process of care leads to higher quality: the needs of the population, governance in the health and non-health sectors, platforms of care, the healthcare workforce, and the tools needed to provide quality care. To avoid the rising “epidemic of poor quality” that the Commission found and to put LMIC on a successful path to achieving the SDGs, we can no longer ignore the pressing need to address healthcare quality just as much as access.

Action Alert: Call your senators today and urge them to lift the ban on CDC research on gun violence

by ihsection, posted in Action Alert, APHA IH Section, Policy and Advocacy, Research, Section Announcements

Sent on behalf of Paul Freeman, IH Section, Action Board

In 2016, the scientific community labeled gun violence a public health crisis and called for a greater public health response including federal research. We desperately need action on gun violence and prevention, but evidence-based decisions can’t be made because of an anti-science ban on research at the Centers for Disease Control and Prevention (CDC)

Call your senators today and urge them to lift the ban on CDC research on gun violence.

Congress is working right now to put the finishing touches on its spending bill, which means that now is the perfect time to ask your senators to lift the ban on gun violence research at the CDC.
Call 855-589-5698 to reach the Capital switchboard and Press 1 to connect to your Senators. Dial in again and Press 2 to connect to your Representative.
Example Script

Hi, my name is ______, and I’m calling from [town/city]. 

I’m calling to express my strong opposition to the budget rider that bans the Centers for Disease Control and Prevention from researching gun violence. 

With deaths and injuries mounting from gun violence in our schools and communities, we need the federal government to study this problem and offer effective, evidence-based solutions to this crisis.

Putting our public dollars behind this problem is critical – we cannot continue to offer only thoughts and prayers, we must act. 

I urge [Senator X] to remove the anti-science rider that prevents the CDC from conducting research on gun violence from the spending bill. 

Thank you for your time.

IF LEAVING A VOICEMAIL: please leave your full street address to ensure your call is tallied

Gun violence is a leading cause of premature death in the U.S. Guns kill almost 30,000 people and cause 60,000 injuries each year. As a longtime advocate for violence prevention policies, APHA recognizes a comprehensive public health approach to addressing this growing crisis is necessary.

The issue of gun violence is complex and deeply rooted in our culture, which is why we must take a public health approach to ensuring our families and communities are safe. We must place a renewed emphasis on improving gun injury and violence research. Ongoing work is needed to ensure firearms do not fall into the wrong hands and to expand access to mental health services to those who need it most.

If you are interested in a sample op-ed, letter to the editor or technical support to help reach your local media, please contact APHA Media Relations.

Visit APHA’s website to learn more about this issue and how you can take action.

The next big thing in global health innovation? A little less innovation, a little more implementation

by Jean Armas, posted in APHA IH Section, eHealth, Health Systems, Research, Technology

A post like this should come with the qualification that I am no luddite when it comes to technology and innovation in global health. Quite the opposite actually. I have dedicated my entire career to championing ideas. Whether that was working in academic research evaluating new ways of helping people with chronic diseases live well or researching the technology and innovation pipeline to help healthcare organizations make decisions on what technologies and innovations to invest in; I have been and will continue to be a health technology and innovation advocate (and when I talk about innovation, I’m not just talking about clinical and biological technology or information and communication technology but more broadly about new programs, interventions, etc).

Five years ago I embarked on a new career path in global health which transformed the way I now think of innovation. One of my first projects was to help a local partner organization implement a logistics management information system to manage their post-rape care medication inventory. Since then, I have helped our partners through the process of implementing other technologies and in that short time, I learned the many pain points of implementing innovations.

When you have spent a good part of your career as I did working in controlled research environments where the protocol is often laid out months ahead of time with little room for deviance and with study participants who are often given incentives to participate, working on the last mile problem required a skill set refresh and a change in the way I viewed the innovation pathway. Whether it is learning how to integrate an innovation into a user’s workflow; getting users to trust you enough to tell you when something is just not working for them; finding out how to get innovations to stick; making mistakes and reiterating; using real-time data to enable feedback loops; understanding (and dealing with) organizational politics and leadership; mapping out relationships, etc. – graduate training in public health does very little to prepare you for the trial by error approach required for these undertakings. Researching and evaluating is very different from implementing. So many of us in this field spend much of our time working on research studies and programs based on the models and theories we’ve learned in school that we very rarely think closely about whether or not the studies or programs we work on are scalable, sustainable, or even ethical.

I recently attended a panel at Stanford consisting primarily of philanthropic organizations discussing how those of us working in the social sector and those of us supporting the work need to rethink innovation in terms of scale. One of the things that struck me during the discussion was that when it came to what metrics we use to define success we’re often talking about success on a small scale.  And too often they’re developed with the mindset of pleasing the donor or funder. When we think success metrics, we usually talk about some quantitative statistic that goes something like this: X% reduced morbidity or mortality in our sample size of N. At the end of the study or funding period, we leave the site, taking with us our intervention. We then go on to write a paper about it, submit it crossing our fingers it gets accepted in a high impact journal, we publish it, we present our ideas at conferences. We then call it a success and move onto our next grant.

While this is often the gold standard of success for academics and should still remain an important part of the innovation pathway, there are parts of this road to innovation success that are concerning, especially in the low-resource settings we work in. Firstly, is it ethical to put in an innovation into a site and then remove the intervention once the study period is over if we know it has helped them? Would the site be even able to afford the innovation once it passes the research phase? Secondly, is it enough to define the success of an innovation by saying the intervention did what we wanted it to do? After all, I’m pretty sure a company like Facebook didn’t call themselves a success after running a small study of 250 users that found that everyone liked the product and it changed their lives. They are successful because they have 1.94 billion daily active users worldwide (scale) and have been around for 14 years (sustainability) and they have changed the way we connect with others.

Dear global health colleagues, we have an enormous task at hand. One that requires us to roll up our sleeves and stop thinking small and start thinking big. Let’s end this epidemic of health technology pilotitis and start innovating in the implementation space. Let’s start thinking about ways of innovating outside of the academic space and in real-world settings with real-world obstacles. Implementing innovations demands collaboration so let’s also make sure that we influence those around us. We need to change the conversation on impact and start asking our colleagues and the organizations that support our work to start thinking about the long game. From there we need to make it easier to decide which technologies and innovations to adopt. Let’s also not forget about training our next generation of public health professionals to focus on creating true impact by teaching effective implementation in schools.

Implementation work is incredibly unsexy and a risky investment but needs to be the next big thing in global health as its value proposition is substantial. It is of notable importance when the future of funding for global health is becoming more uncertain. We need now more than ever to deliver long-lasting solutions, not just short-term fixes.

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A study looking at the proportion of children’s health grants funded by the US National Institutes of Health and the Bill and Melinda Gates Foundation found that 97% of grants were for developing new technologies and only 3% for improving delivery and use of existing technologies. Additionally, they found that new technologies would only reduce child mortality by 22% compared to 63% if existing technologies were fully utilized.

Although this study looked only at children’s health grants, the implementation gap can be found universally throughout global health. Learn more about how to bridge the “3/97” gap:

 

Global Nutrition-A report Card

by abbhirami, posted in APHA IH Section, Food/Nutrition, Policy and Advocacy, Research

The 2016 Global Nutrition Report, a report that assess progress towards global nutrition targets as set by the World Health Assembly,  was released in June. This annual report is the result of a comprehensive review of state of nutrition by an independent, collaborative initiative that involves a diverse set of partners.

According to the latest report a staggering one in three of us suffers from malnutrition. Malnutrition is defined as “lack of proper nutrition, caused by not having enough to eat, not eating enough of the right things, or being unable to use the food that one does eat.” The one in three number reflects a spectrum of malnutrition ranging from childhood stunting and wasting to adult overweight and obesity. Malnutrition is the number one driver of global disease burden and its occurrence tends to have a cascading effect.

Malnutrition 1Image Source: Global Nutrition Report 2016, p 21.

In the last five years or so, there has been traction and investment into ending malnutrition. The global nutrition targets for 2025 set by the World Health Assembly include:

  • Achieve a 40 percent reduction in the number of children under 5 who are stunted
  • Reduce and maintain wasting in children under 5 at less than 5 percent
  • Experience no increase in overweight in children under 5 years
  • Experience no increase in obesity and diabetes (in adults and adolescents)
  • Achieve a 50 percent reduction of anemia in women of reproductive age
  • Achieve a 30 percent reduction in low birth weight
  • Increase the rate of exclusive breastfeeding in the first 6 months up to at least 50 percent
  • Achieve a 30 percent reduction in average population salt intake

According to the report there is significant variations between countries in the status of meeting the global targets. Many countries have made great progress and are on track to reducing under-5 stunting wasting, and overweight, and exclusive breastfeeding of infants younger than 6 months old. Of particular importance are data that show that under-5 stunting is decreasing in most regions except in Africa and the number of children under-5 who are overweight is increasing in Asia. Despite this success, the report points out that nearly all countries are off course with respect to global targets related to reducing anemia in women and adult overweight and obesity.

The calls to action issued by the authors of this report include:

  1. Governments making a commitment to end all forms of malnutrition; dramatic reductions in malnutrition in Brazil, Ghana, Peru and Maharashtra (Indian state) were due to political choices that were made.

Malnutrition 2
Image Source: Global Nutrition Report 2016, p 33.

  1. “Invest more, allocate better”: Current spending is not enough to tackle malnutrition. According to the report  government spending and funding from donors are low and remain stagnated.
  1. Collect right data: Countries must strive to fill national and subnational data gaps to understand their unique nutrition contexts that would help them act on it by maximizing investment.
  1. Support evidence-based solutions and identify new solutions: Countries could learn from successes and use proven policies and interventions to tackle malnutrition.
  1. Address all forms of malnutrition: Curbing the rise of dual burden of undernutrition and obesity (and other nutrition-related NCDs) in many low and middle income countries would require policies, strategies and interventions that can take on the double-duty of tackling all forms of malnutrition.

Given the large numbers of refugees and internally displaced people, the report does discuss the vulnerability of this group to food insecurity and malnutrition. The authors also call for better assessment of nutritional status in emergency settings, incorporating nutrition-sensitive interventions and improved accountability of nutrition actions in emergency contexts.

The report does not discuss malnutrition among the elderly or the complete lack of data that would be helpful in understanding the magnitude of this problem. What the report is also missing or perhaps not within its scope, is the importance of maintenance of agro-biodiversity in combating malnutrition. The loss of biodiversity and its impact on providing better nutrition for today and tomorrow is something that cannot be ignored.

You can read the report in its entirety here and let us know what you think!