How you can help make viral load testing a reality this World Aids Day

The time for viral load testing is now.”For years this has been the focus of this company and each of our employees. Today, it has become policy for developing nations around the world as recommended by the World Health Organization (WHO).

Last year, the WHO published their 2013 revised guidelines, calling for developing countries to roll out routine virological monitoring. Since then, more people have come to understand the role of HIV viral load testing and the benefits it provides to patients and the healthcare systems that support them. 

In 2014 the debate over HIV viral load testing in resource-limited settings evolved from “Should we?” to “How can we?” Our friends at The Load Zero Foundation have answered that question with this clever “At-a-Glance” HIV viral load comparison infograhic. This much needed overview promotes awareness of the six HIV Viral Load assays that:

1. Exceed the WHO’s recommendation for test sensitivity

2. Have performance that has been verified by peer-reviewed journals

3. Are commercially available today

For World Aids Day 2014, I encourage you to share this infographic with your networks and spread the word that “The Time for Viral Load Testing is Now.” 

                          

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.

World Aids Day 2013: Halfway to Zero

Each year World Aids Day helps raise awareness around the world. It’s also a time for everyone involved in the fight against HIV to step back and assess our progress. Looking at the HIV community as a whole and Cavidi in particular, I can say it’s been a good year overall. We have seen great progress in the treatment of HIV worldwide. At the same time, these developments have further clarified the challenges that remain to providing universal access to proper HIV treatment and prevention. 

World Aids Day Graphic from http://worldaidsdaynw.org/

World Aids Day 2013 marks the halfway point of UNAIDS’ Getting to Zero initiative. This ambitious initiative has three core objectives to achieve by 2015:

• Zero new HIV infections
• Zero AIDS-related deaths
• Zero HIV-related discrimination

So where does the world stand at the halfway mark? Many of the statistics coming from the WHO are cause for optimism taken at face value. But with an estimated 2 million people contracting HIV each year and over 1.5 million deaths attributed to AIDS, it’s clear that we are still a long way from zero. 

Given the complexity of these issues and the limitations of the available data, it’s often quite difficult to get a fix on where we are on our journey to zero. Roger Tatoud explains just how difficult this task can be in an excellent post he wrote a few weeks ago on the 0 Incidence blog. In his post, Roger boils down a sea of data into three clear graphs that together start to give us insight into where we stand today. I was particularly interested in his analysis of how we are doing in terms of providing access to HIV treatment. The year-on-year increase in the number of people able to access HIV treatment has been rising steadily since 2006. That’s all good. However, the rate of change year-on-year over the same period has been in steady decline, meaning that although more people are accessing HIV treatment each year, the rate at which people are accessing HIV treatment is slowing down. That’s not good. Roger concludes, “This suggests that current approaches to deliver treatment are reaching a limit (or that something is limiting further expansion) and that for treatment to reach more people more effort will be needed or that we will need to do things differently.” 

Part of that difference may well be an increased role for viral load monitoring in the treatment of HIV. 2013 saw viral load monitoring receiving increased attention among the world’s most influential healthcare bodies such as WHO, UNAIDS, UNITAID and MSF. A decade after acknowledging the importance of HIV viral load monitoring, the World Health Organization 2013 revised guidelines, calling for developing countries to roll out routine virological monitoring, with viral load tests at both six and twelve months after treatment initiation, and then at least every twelve months thereafter. In this way, treatment adherence problems are corrected more quickly and patient treatment can be adjusted if the viral infection is not responding to therapy. 

This decision was further supported by a report from Médecins Sans Frontières (MSF) that highlights the importance of routine HIV viral load monitoring in low-income countries. Today, most clinics in resource-limited settings try to monitor disease progression with CD4 tests alone. The MSF research provides ten specific benefits that programs in developing nations can hope to achieve by adopting the WHO recommendation for routine HIV viral load testing. Among them are confirmation of treatment failure, prevention of HIV mother-to-child transmission, and improvement in HIV treatment outcomes in low-income countries. If realized, the benefits outlined in the MSF report would certainly move us closer to UNAIDS Getting to Zero goals. 

The increased interest in viral load monitoring witnessed over the past year has been accompanied by increased interest in point-of-care solutions. The idea is to get the HIV monitoring test out to where the problem is. I sense this is a reaction to address the inadequacies of centralized testing, particularly in resource-limited settings where simply transporting samples to a central lab can be a limiting factor. While the point-of-care initiatives are a welcome development to dysfunctional centralized options, there is middle ground that needs to be kept in mind.

Any solutions for HIV treatment have to work with the realities of existing laboratory infrastructure. The WHO has designated five tiers of laboratory infrastructure.  Each has its capabilities in terms of what types of tests can be run and the throughput that is possible. This, in turn, influences the access to testing that we can expect from any tier. For instance Tiers 0 and 1 may interact with a large population of people living with HIV, but since there is no lab infrastructure and a shortage of skilled staff exists at that level, testing is limited to one-at-a-time, point of care testing with low throughput.  We have drawn on throughput projections and population geography to provide a picture of  potential access to monitoring at the different levels. 

If we estimate the global population of people living with HIV to be at around 34 million, we can divide them by this type of access. There we see that the centralized testing schemes used by reference labs in Tier 4 could access about 6 million people living with HIV and this is where, traditionally, much of the emphasis has been placed. Primary care facilities and community outreach programs in Tier 0 and 1 could reach about 8 million people living with HIV and this is where point-of-care solutions can have the greatest impact. But with near-patient testing, regional and district-level facilities in Tier 2 and 3 could provide access to over 20 million or 60 % of cases. Today, Cavidi’s ExaVir™ Load test is the only test capable of providing viral load monitoring coverage on a regional and district level.

These middle tiers are where Cavidi focuses its efforts both with our current product, ExaVir™ Load, and with our R&D efforts to develop new monitoring solutions that will increase throughput and access even further. I’m pleased to announce that we have made significant progress in both areas over the past year. 

In 2013 we reached another milestone with our ExaVir™ Load HIV viral load monitoring kit as we began shipping to the Philippines. This marks the 25^th country to adopt ExaVir™ Load for clinical use in addition to over a dozen other countries where the test is currently being evaluated for use. The test offers the same sensitivity and accuracy of Tier 4 reference tests but, unlike those tests, it can be run in Tier 2 and 3 facilities – and at a fraction of the cost. 

Cavidi’s new Automated Monitoring System will provide viral load and be adding other optional HIV test kits, such as CD4, EID, and drug resistance in one robust bench-top unit.

We are also making steady progress on the next generation of HIV viral load monitoring diagnostics. Codenamed the Automated Monitoring System, the new system is now in the prototype stage. This new product uses the same proven RT-technology found in our ExaVir™ Load test but it is fully automated, requiring less time from lab technicians and greater throughput. In addition to viral load testing, we will be adding other optional HIV test kits like CD4, EID, and drug resistance in one bench-top unit.  Like ExaVir™ Load, our new system is ideally suited to the near-patient testing needs of Tier 2 and 3 regional and district level facilities. Bringing this product to market will be a game changer for increasing both access and quality of HIV treatment globally. I look forward to sharing more news on the project throughout 2014. 

While 2013 saw progress in the battle against HIV, it’s clear that we still have lots of work ahead of us. That’s why we need to ensure that the public remains aware and vigilant. My colleagues and I at Cavidi will continue to work to increase awareness, access, and quality of HIV treatment worldwide. In the interest of raising awareness among your peer network, I hope you will share this post. If you would like more information about Cavidi’s work in this area, feel free to contact me directly. 

Viral load monitoring enters the mainstream

Last night I attended a dinner in Stockholm hosted by the Swedish Ministry for International Development & Cooperation. I was fortunate to have the chance to chat with Dr. Mark Dybul, Executive Director of the Global Fund. The subject of HIV viral load monitoring came up. As you might imagine, this topic has been a central theme of my dinner conversations for several years. But last night’s discussion took on a very different tone. 

Viral load monitoring officially endorsed by the world’s most respected public health authority

With almost ten million people in developing nations currently receiving antiretroviral treatment (ART) for HIV, it’s fair to say that great progress has been made in addressing the HIV pandemic. However, one area has remained well behind the curve when comparing treatment standards in developed nations to those in the developing world. That deficiency is most strikingly evident in HIV viral load monitoring. Antiretroviral drugs (ARVs) can be used much more effectively when combined with viral load monitoring. Conversely, administering ARVs in the absence of viral load monitoring means replacing data with guesswork, which puts patients at risk and can waste resources. That is why every HIV patient in the developed world receives regular viral load monitoring as a central part of treatment. And, why it’s a shame that this diagnostic has not been widely regarded as a critical component of routine practice in the areas hardest hit by the HIV pandemic.

Which brings me back to my dinner with Dr. Dybul…During our discussion it suddenly occurred to me that I no longer felt like a radical evangelist advocating viral load monitoring from the sidelines of the war on HIV. It felt more like preaching to the choir. That’s because, for the first time, routine viral load monitoring has been officially endorsed by the world’s most respected public health authority. The World Health Organization (WHO) recently revised their guidelines for HIV treatment and now strongly recommends implementing routine viral load monitoring in resource-limited settings. 

WHO recognized the importance of viral load monitoring as early as 2003, but fell short of including the test in its official HIV treatment guidelines for developing nations. Priorities back then were focused on getting ARVs into resource-limited countries. Now that the ARVs have arrived, viral load monitoring takes on much more significance. The revised WHO guidelines call for developing countries to roll out routine virological monitoring, with viral load tests at both six and twelve months after treatment initiation, and then at least every twelve months thereafter. In this way, treatment adherence problems are corrected more quickly and patient treatment can be adjusted immediately as indications arise.

WHO Consolidated ARV guidelines 2013

A recent report from Médecins Sans Frontières (MSF) highlighted the importance of routine viral load monitoring for a number of reasons, some of which include confirmation of treatment failure, prevention of HIV mother-to-child transmission, and improvement in HIV treatment outcomes in low-income countries. MSF currently provides treatment for 285,000 HIV patients in 21 countries. Today, most clinics in resource-limited settings try to monitor disease progression with CD4 tests alone. This research provides ten specific benefits that programs in developing nations can hope to achieve by adopting the WHO recommendation for routine viral load testing. These include:

• Support of treatment adherence
• Confirmation of treatment failure early, before CD4 decline
• Revelation of previously hidden viral loads, then help reducing them
• Enablement of program decentralization and task shifting
• Improvement of treatment efficacy
• Help meeting programwide goals
• Improvement of early infant diagnosis
• Delivery of systemic benefits, from the individual to the institution
• Cost benefits for programs by reducing:
  • cost of drugs by preserving first-line therapy
  • costs associated with redundant testing
  • cost for viral load equipment and operations
  • testing costs through the use of pooled samples
• Prolongation of treatment options for patients

Clearly, the addition of routine viral load testing offers significant gains for both programs and patients in resource-limited settings. Now that WHO has endorsed viral load monitoring, the biggest barricade to access will be ensuring that we provide viral load tests at an affordable cost. Our own viral load monitoring product, ExaVir™Load, was purposely designed with that aim in mind. It is an RT-based ELISA test that measures viral load with comparable sensitivity and reliability to standard DNA-based tests. The difference is that ExaVir™Load can be run in simple and/or rural laboratory environments with low initial investment. An automated version of the test is currently in development, as outlined in the recent UNITAID HIV Diagnostic Landscape report.

Viral load monitoring is no longer a fringe consideration when treating HIV in resource-limited settings. That’s great news for people with HIV in the developing world. The revised WHO guidelines have helped viral load monitoring enter the mainstream. On behalf of Cavidi, I promise to keep it there with tests that are both reliable and affordable. I am proud that Cavidi can play a central role in carrying out the WHO’s recommendation. Moreover, I’m pleased to see that leadership in organizations such as WHO and the Global Fund are all in agreement that the time for viral load monitoring is now. 

John Reisky de Dubnic

CEO

Cavidi

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