Investment with Impact: Closing the HIV treatment gap

A presentation on the importance of global viral load monitoring to contain the HIV pandemic. 

I was pleased to speak at the United Nations this week as part of the Cavendish Global Health Impact Forum. The idea of the forum is to introduce good investment opportunities that have positive social impact with individuals and foundations who want to make a difference. Typically, these are investors who wish to invest in businesses within the health and life sciences, where the financial return is magnified by the social good derived from helping the business venture.  This is a criteria well-suited for Cavidi’s aim to help contain the HIV pandemic by creating greater access to HIV-related monitoring solutions.

“Cavendish assists family offices in identifying the best scientific minds, accomplished healthcare delivery professionals, innovative private sector companies, philanthropic organizations, and health policy experts engaged in transforming medical outcomes on a regional, national and global basis.” Cavendish Mission

The Global Health Impact Forum is hosted by the Global Partnerships Forum together with Cavendish Global, The New York Academy of Sciences, and International Telecommunication Union at the United Nations Headquarters in New York. Participants are a mixture of scientists and CEOs, carefully vetted and invited to present their case before the investors. I was honored to be included in this select group and proud to represent everyone at Cavidi who has worked so hard to get us to where we are today. 

Given the venue, I was pleased to see global health elevated on par with global peace, climate change, and human rights as one of the most pressing issues of our time. Innovation and technology play key roles in making this happen.

As Amir Dossal, Chairman of the Global Partnerships Forum, mentioned in his opening remarks at the event, one of the most critical issues facing the UN, and society in general, is providing global access to healthcare, particularly in developing countries. Mr. Dossal specified the need for technology and training to help medical workers on the front lines monitor and manage disease. I don’t think I could have asked for a more appropriate introduction to my talk and the important work that Cavidi is doing today. 

Below is a video of my presentation, where I make the case for the impact that Cavidi and our new automated viral load monitoring platform can make to the nearly 36 million people infected with HIV around the world today, and future generations to come.  I would welcome any comments or questions you have about the event or Cavidi’s involvement. 

For those who would like more details on the event,  you can see the entire Cavendish Global Health Impact Forum 2014 program from this link. And if you would like to know more about our new automated HIV viral load monitoring platform, feel free to contact me.

Time for a new gold standard in HIV viral load monitoring

This past year has brought more good news in the battle against HIV/AIDS with UNAIDS stating, “On the cusp of the fourth decade of the AIDS epidemic, the world has turned the corner—it has halted and begun to reverse the spread of HIV.” UNAID’s 2012 report cited 700,000 fewer new HIV infections in 2011 than in 2001. AIDS-related deaths have been reduced by one-third in the past six years. And access to antiretroviral therapy (ART) continues to grow at unprecedented rates. But as the battle against HIV enters a new phase, it introduces new challenges to the healthcare community, particularly with regard to diagnostics. In response, the World Health Organization and UNITAID have dubbed the next ten years, “the decade of diagnostics.” In their session at AIDS 2012 in Washington D.C. they emphasized the important role that cheaper, simplified diagnostics must play in the next phase of the campaign to stem the HIV pandemic. This emphasis is redefining the role of HIV viral load testing in treatment and is placing new demands on how these tests are conducted. 

Number of people newly infected with HIV, Global, 1990-2011

UNAIDS Report (2012)

For decades the gold standard for HIV viral load diagnostics have been RNA-based tests. But in this new diagnostic landscape I see centralized RNA-based testing rapidly losing relevance to tools that are better suited to meet the diagnostics challenges that we see today in both the developed and developing world. Most notable among these are: a) the need to scale HIV viral load monitoring in step with the burgeoning number of men, women and children entering treatment, b) managing the rise in drug-resistant HIV strains that accompany greater access to ARV treatment and c) address the diagnostic needs of infants born to HIV-positive mothers. 

In low-to-middle income countries, access to HIV viral load testing has become a more critical issue given the recent increase in access to ART.  According to the World Health Organization (WHO), there was a 20-fold increase in the number of people receiving ART in developing countries between 2003 and 2011, and a 20% increase in just one year (from 6.6 million in 2010 to more than 8 million in 2011). The rapid increase in access to Antiretroviral drugs (ARV) has triggered a corresponding increase in the need to monitor those receiving treatment. This helps to ensure the virus is being suppressed and helps the doctor know when the patient needs to be switched to a new treatment regimen.  

Originally developed for use in North America and Europe, RNA-based tests are proving impractical for decentralized use in low-to-middle income countries. Around 70% of the world’s HIV population live in sub-Saharan Africa. As a result, district hospitals and clinics outside the capital have to either send blood samples away to a central reference hospital or, more likely, forgo HIV viral load monitoring altogether. In light of this, it seems the gold standard is shifting in favor of a HIV viral load monitoring solution that can deliver the same reliability in a decentralized model with testing conducted near-patient.

This has created a flurry of innovation in the HIV viral load POC testing arena. Maurine Murtagh has identified 13 different entrants in this area in the 2nd edition of UNITAID Diagnostic Technology Landscape Report.  Of the options available today, Reverse Transcriptase (RT)-based testing seems to offer the most plausible solution on several fronts. First, RT is a very stable marker since it is not affected by mutation and is always present when the HIV virus is replicating. Since RT-based tests do not target a specific nucleic acid sequence, they are able to quantify all types and subtypes of HIV, including new strains, without any modification to the test. RT-based tests have historically been significantly less expensive than RNA tests both in terms of start-up and running costs. Further, the RT platform has an unmatched track record among this next generation of HIV viral load tests. It has been in the field for over a decade with more than 40 peer-reviewed journal articles and over 350,000 tests run. Several studies over the past decade have compared ExaVir™ Load to the gold standard PCR tests and all have found excellent correlation with RNA-based tests. 

The benefits of RT-based HIV viral load testing go beyond resource-limited settings. In the developed world, HIV viral load monitoring is a main line of defense against the rise in drug resistant strains of HIV.  Eric Rubin, professor of immunology and infectious diseases at HSPH put it eloquently, "Drug resistance is the product of success: With treatment, we have drug resistance." Since ARV treatment has been more prevalent in developed countries, resistance has mainly been a problem for these nations.  For instance, a recent study in San Francisco revealed that 60 percent of new HIV infections are drug resistant. One of the key factors in stemming this tide is early detection of treatment failure through HIV viral load monitoring of all HIV positive patients. Since healthcare systems the world over are straining to manage budgets, a more cost-effective decentralized HIV viral load monitoring solution may benefit developed nations as much as it does low-to-middle income countries.  

In areas where the subtype of the individual may be unknown RT-based testing provides additional advantages. This has not been much of a concern in the US where the vast majority of HIV-1 infections are subtype B—98 percent according to some surveys. But an article from CAP Foundation asserts that it may be time for the US to  “catch up to what’s happening in Tanzania and elsewhere in Africa. Specifically, HIV-1 subtypes common in Africa may be making inroads in the United States, as they have in Europe.”  Of the testing options available, only RT-based testing is able to detect any HIV activity without modifying the test — including new HIV strains.

World map of Global distribution of HIV-1 strains

IAVI Report (2003)

Lastly, with half of the world’s HIV population being women and many of them of child-bearing age, there has been increased focus in recent years on mother-to-child transmission. Here too we see great strides have been made with 57% of HIV positive pregnant woman living in low-and middle-income countries receiving treatment in 2011. One persistent problem has been the early infant diagnosis (EID) since standard rapid tests won’t work on newborns. This is another area where RT-based testing has been found to convey an advantage. Over the past year more studies have confirmed that in addition to RT-based EID solutions being significantly less expensive than RNA-based tests, they are also able to detect and quantify HIV infection in infants more reliably and at a much younger age.  

This World AIDS Day, as Cavidi celebrates the 25^th Anniversary of our RT-technology, I’m pleased to report that we are making steady progress on three fronts to address the challenges above.  First, we continue to support the increasing uptake of our manual ExaVir Load HIV viral load monitoring test which is increasing access to affordable HIV viral load testing around the world.  Second, we have made excellent progress developing a new automated platform for near patient HIV viral load monitoring. The platform design is now entering final stages of prototype development and testing. And third, over this past year we have initiated further studies into the development of an RT-based EID test. I look forward to sharing more details on these exciting developments over the next year.

New challenges require new solutions. As we enter the decade of diagnostics I hope to see a new gold standard emerge that will make HIV viral load testing more accessible and reliable. My team will do their part as they continue to bring innovative RT-based diagnostics to the world in 2013 and beyond. 

 John Reisky de Dubnic

CEO

Cavidi

”Getting to Zero” will require more than funding to succeed

Observations on the role of innovation in the battle against HIV/AIDS

Getting to Zero is the theme of this year’s World AIDS Day:  Zero HIV/AIDS-related new infections, deaths and discrimination by 2015.  I wholeheartedly endorse the idea and admire the ambition level. But this World AIDS Day falls on the heels of some bittersweet news.  

 On one hand we have last week’s report from the Joint United Nations Programme on HIV/AIDS (UNAIDS) telling us that 2011 has been a “game-changing” year in the fight against HIV/AIDS with unprecedented progress in science, political leadership and results.  On the other hand the Global Fund had a “getting to zero” announcement of a different sort. Last week they announced there would be zero funding for new HIV/AIDS-related initiatives until 2014.  A statement from Médecins Sans Frontières (MSF) summed up the situation: “The dramatic resource shortfall comes at a time when the latest HIV science shows that HIV treatment itself not only saves lives, but is also a critical form of preventing the spread of the virus, and governments are making overtures that there could be an end to the AIDS epidemic.”   The statement goes on to urge governments to step up and find the money required by the Global Fund. A second statement issued two days later went further asserting that “The international community must recognize that we are at a critical crossroads: we either use the science, tools, and policies already at our disposal to save lives and prevent new infections; or see the hard-fought gains of the last decade lost.”

No doubt, fundraisers will need to work hard to stimulate giving in the current global economy.  When they succeed, I hope they will turn their attention to a much less publicized but equally important issue: stimulating competition and innovation in the markets where those funds will be disbursed. Because that is what will be needed to get to zero in the countries hardest hit by HIV/AIDS — particularly if funds are frozen and we find ourselves in a catch-up situation one, two or more years down the road. 

I have complete confidence in the ability of the biotech industry to accelerate progress in the war against HIV. But to do that they will need a balanced playing field on which to compete. Currently, that is not case in several critical and underserved areas of HIV diagnostics.  For instance, a 2008 report from the Global AIDS Alliance (themselves the victim of funding woes in 2010) cites one company that “controls roughly 80% of the overall NAT [nucleic-acid-based tests] market share, which gives the company a near monopoly on global diagnostics and even greater domination in the area of EID.”   

More recently, at the IAS in Rome this past summer, Maurine Murtagh reported that the market conditions in resource-limited settings for three of the most critical and under-served areas on HIV management are monopolized by a few large companies.  One company controls 80% of all CD4 testing.  Two companies have 70% market share in viral load testing. And one company has 90% market share in early infant diagnosis (EID).

At the same time Ms. Murtagh highlights the inadequacies of the solutions provided under these monopolies. “Diagnostic delivery of EID, CD4 and viral load testing is generally via large and relatively expensive laboratory-based systems that require well-trained technicians and good sample transport networks to provide access to testing for those in some urban, and virtually all peri-urban and rural settings.”  

I have spent most of my career in the private sector where monopolies are frowned upon if not banned outright.  As we all know, monopolies create huge barriers of entry for new products, stifle innovation, discourage investment and keep prices inflated. When I became CEO of Cavidi, a biotech firm specialized in HIV diagnostics, I was surprised to discover how monopolies are a fact of life in the very markets that are most in need of innovation and investment. I was equally surprised at how resistant to change these resource-limited markets are despite the clear limitations of the current diagnostic solutions. 

This is not to slight the contributions made by the companies who dominate these markets. In Cavidi’s diagnostic area, imbedded technology can be credited with contributing to the progress detailed in last week’s UNAIDS report. However much of this technology was created for use in developed nations and has changed little over the past 20 years to adapt to the very different environment we see in resource-limited settings.  This is the predictable result of any monopoly — stagnation.  In the case of HIV diagnostics, stagnation means that many of the people who need the tests most cannot access them for the reasons cited by Ms. Murtagh. 

This situation is not the byproduct of a market that lacks innovative solutions from creative companies. A look at the UNITAID HIV/AIDS Diagnostic Landscape publication gives you an idea of the vast number of more effective solutions including our own RT-based diagnostic assay which, in addition to lab-based viral load monitoring in resource-limited settings, has the potential to provide a viable, cost-effective solution to elusive problems like EID and near-patient viral load monitoring. 

Of course these solutions need financing to scale up. But they also need an efficient market that promotes competition and encourages new ideas and better solutions.  Until those conditions exist very few new ideas from smaller, entrepreneurial companies like ours will ever be allowed to contribute on par with their potential. So with regard to diagnostics, the real challenge in getting to zero by 2015 isn’t,  “Where can we find the next big idea?” It is, “How can we hasten the uptake of ideas we already have in the presence of a monopoly?”

The benefits of such competition and ingenuity in places like Sub-Saharan Africa, India and Southeast Asia don’t stop there. The solutions developed for resource-limited settings are often just as applicable in developed nations. For instance our ExaVir™ viral load test is as sensitive as the gold standard but it can also detect all known HIV subtypes.  This is something that the gold standard cannot do and the reason why our test is also being used in some of the world’s most prestigious medical institutions, such as the Royal Free Hospital in London and the University of Maryland School of Medicine IHV (Institute of Human Virology) in the U.S.  Further, given the burden felt by most healthcare systems in developed nations the need for more cost-effective diagnostic solutions is not limited to developing nations. 

Today, the science exists to address some of the most pressing challenges in getting to zero but is often confounded by a market that clearly does not welcome new entrants gladly. This is not the type of problem that is solved by money alone. It’s also a matter of mindset. So on this World AIDS Day I join the plea for donor nations to ensure that their pledges to the Global Fund are honored. And to that I would add a plea for recipient nations to ensure that the entire HIV treatment spectrum, including diagnostics, is allowed to evolve and thrive under market conditions that encourage competition and innovation. With both funding and innovation nothing can stop us from getting to zero in record time.  That is my wish today, and my colleagues and I are honored to be part of this historic endeavor.

John Reisky de Dubnic

CEO

Cavidi