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“Treat All” provides new hope as well as new challenges in the fight against HIV

World Aids Day 2015 once again directs the public’s attention toward the ongoing HIV pandemic and the efforts to contain it. As the year draws to an end, we can see great progress over the past twelve months and a clear agenda for 2016.

This past May, we learned that the START study, sponsored by UNAIDS, was being prematurely concluded by study organizers because results were already so clear: Data showed that those who received anti-retroviral therapy (ART) immediately upon HIV diagnosis were 53% less likely to die during the trial or develop AIDS or a serious illness than those who waited for initiation of treatment.

The START study addressed a point that had been widely debated by the HIV healthcare community for years. That debate was swiftly resolved when Michel Sidibé, Executive Director of UNAIDS, concluded that, “Every person living with HIV should have immediate access to life-saving antiretroviral therapy. Delaying access to HIV treatment under any pretext is denying the right to health.”

It didn’t take long for the World Health Organization (WHO) to act on the findings. In September of this year, the WHO updated its treatment guidelines to include a “treat all” provision. It recommends that everyone with HIV is provided ART immediately after diagnosis. This is one of the most significant developments in the treatment of HIV over the last decade. Michel Sidibé explained that the policy change could help prevent 21 million AIDS-related deaths and 28 million new infections by 2030.

Of course, with the new WHO guidelines come new challenges for healthcare providers around the world. According to UNAID’s estimates, 57% of HIV positive adults do not receive treatment today. Based on that figure, the new WHO guidelines will mean proving ART to an additional 21 million people globally.

One of the greatest challenges in making “treat all” a reality is that the overwhelming majority of the untreated live in resource-limited settings. In developing nations around the world, healthcare organizations are working to find ways to increase access to ART, as well as to the viral load monitoring required for proper administration of the life-saving drugs. I’m happy to report progress on that front as well.

In September of this year, Cavidi was selected by the European Investment Bank (EIB) as a recipient of their Infectious Diseases Innovation Loan for 2015. The focus of the loan is our Ziva™ viral load monitoring system. Viral load monitoring is an essential part of HIV treatment, but, until now, it has been difficult to administer in near-patient settings. Ziva™ changes that by providing a medium throughput, fully-automated viral load monitoring system purpose-built to meet the requirements of decentralized labs like those found in district hospitals across the developing world. Its unique Reverse Transcriptase (RT) technology makes fully-automated gold-standard results possible for decentralized testing.

The recognition of the EIB is a great honor for Cavidi, but an even bigger win for people infected with HIV around the world. While the €10 million loan is only part of the investment required to get Ziva™ to market, it will go far to provide access to viral load monitoring sooner for millions living with HIV.

All things considered, 2015 has been a pivotal year in the battle against HIV and cause for renewed optimism. The new WHO guidelines mark a significant shift in the global treatment mindset. The HIV treatment community has overcome great challenges to reach this point where “treat all” is the official policy moving forward. The financial and logistic challenges we now face to implement the policy are significant, yet dwarfed in comparison. Addressing these new challenges will be our focus at Cavidi for 2016 and beyond. 


What the EIB InnovFin award means for Cavidi and HIV management

Speaking on behalf of the entire Cavidi team, we are honored to be chosen by the European Investment Bank (EIB) as recipient of their Infectious Diseases Innovation Loan for 2015. This €10 million award will provide a substantial portion of the investment required to bring Ziva™ to market in 2016. Just as importantly, it underscores the importance of the groundbreaking work Cavidi is doing in the area of HIV management.

Viral load monitoring is an essential part of HIV treatment, but it has always been difficult to administer in near-patient settings. Ziva™ changes that. Building off of Cavidi’s proprietary Reverse Transcriptase (RT) technology, we have designed Ziva™ as a medium throughput, fully-automated viral load monitoring system. It is purpose-built to meet the requirements of decentralized labs like those in district hospitals. When it reaches the market, Ziva™ will be a game changer, making routine viral load testing accessible to millions of people around the globe. 

In providing the loan, the EIB recognized the importance of viral load testing and the groundbreaking work Cavidi has been doing in the treatment of HIV. The EIB is the European Union's bank. They are the only bank owned by and representing the interests of the European Union Member States. The bank makes long-term financing available for sound investments in order to contribute toward EU policy goals. As part of that aim, the EIB has set up a program to help innovative firms access financing more easily. Over the next seven years, "InnovFin – EU Finance for Innovators" will make more than €24 billion EUR of financial support available for research and innovation (R&I) by small, medium-sized, and large companies.

Thank you to all those involved with InnovFin at EIB. And, thank you to my team at Cavidi for once again making history in the area of HIV diagnostics. 


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

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 25th 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




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 25th 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




HIV Viral load monitoring: from patient to public health issue

Amazing strides have been made in providing access to Antiretroviral Therapy (ART) in resource-limited settings. In 2011, around
8 million HIV-infected patients living in low- and middle-income countries have access to ART compared to just 400,000 a decade a go. Greater access to Antiretroviral drugs (ARVs) is good news, but it has magnified the need for HIV viral load monitoring to properly administer these drugs. A recent Médecins Sans Frontières (MSF) review of data from 12 low- and middle-income countries found that only 2% of patients had ever received a HIV viral load test result, no less received them every 6-months as recommended by the World Health Organization (WHO).

One Hope by Joe Average was used for the XI International AIDS Conference in Vancouver in 1996The direct benefits of HIV viral load testing to the patient are well documented in terms of better outcomes with decreased mortality. That’s why HIV viral load testing has long been a standard part of treatment in middle- to upper-income nations. But if we look beyond the patient, there is an equally compelling public health case to be made for ensuring access to HIV viral load testing in the low- and middle-income countries where the vast majority of HIV patients live. Here are four ways HIV viral load testing protects the public as well as the patient. 

 1. Help clinical resources go further by targeting counseling where it is needed. Some patients will take their medication as instructed – many will not. Noncompliant patients will usually show elevated viral activity which can lead to increases in treatment failure, transmission, comorbidity, drug resistance, and mortality. Counseling has been found to be very effective at helping with adherence issues but is labor intensive.  This can be an enormous strain affecting the entire clinic. With HIV viral load monitoring the clinic can identify noncompliant patients early and more efficiently target counseling only to those who need it. 

 2. Reduce treatment costs by helping less-expensive first-line ART last longer.  HIV mutates at such a remarkable rate that it is a foregone conclusion the virus will eventually be able to resist first-line treatment. The only question is when. If proper concentrations of the drugs are not properly maintained in the blood it makes this job a lot easier for the virus and thus will lead to treatment failure sooner. Monitoring viral load helps identify viral activity and address it before the treatment fails and the patient needs to be moved to a new treatment (if available).  Without viral load measurement, doctors can also misattribute patient symptoms to treatment failure and switch them before it is required. Since first-line ART is always cheaper than second-line treatment (in some cases one-quarter the price), keeping patients on first-line treatment for as long as possible helps resources go further. 

3. Reduce the spread of HIV.  Studies have found that transmission among HIV-infected persons with a viral load below 1,500 copies/ml is rare.  Put simply, if there is no virus circulating in the patient’s blood, then they are unlikely to spread the disease.  So managing HIV viral load can, in itself, contribute to prevention. But you can’t manage what you can’t measure. This is where HIV viral load monitoring contributes. A mathematical model published in the AIDS journal this year demonstrated that routine virological monitoring combined with ART can lead to a 31% reduction in HIV transmission. 

 4. Combat the global problem of HIV drug-resistance. If HIV is allowed to remain active in the presence of drugs meant to suppress it, then it is just a matter of time before it will produce a viable mutation that will be resistant to the drug. We are already seeing this. A 2010 study in resource-limited settings found that in the absence of HIV viral load monitoring, the incidence of drug-resistant mutations following treatment failure is high.  Of course this causes secondary resistance in these patients. But there’s a knock-on effect in that these resistant patients begin spreading a strain of HIV to others that drugs can’t treat. MSF reports that primary resistance in sub-Saharan Africa is already at 5.6% overall. If we look at countries where ART have been dispensed without HIV viral load monitoring for 10 years or longer we see a rate of 12%.  Worse still, the drug-resistant mutations that are being found in newly infected people who have never been on treatment are resistant to both first- and second-line drugs. That’s a trend that could unravel much of the progress made over the last 20 years in the battle against HIV. 

When we look at HIV viral load monitoring from a public health perspective it becomes clear that the issues above are not limited to low- and middle-income countries. First, because any HIV viral load monitoring solution that is inexpensive enough to be viable in resource-limited settings could lower the cost of HIV treatment for any healthcare system. Secondly, because issues like the spread of HIV infection and drug resistance know no borders. HIV/AIDS is a global problem and affordable HIV viral load monitoring is an important part of the solution whether you are in Nairobi, New York, Melbourne, Lusaka, London, Harare or Hong Kong. 

 As access to ARVs grows across low- and middle-income regions, so does the public health imperative to dispense those drugs in a responsible manner with regular HIV viral load monitoring of patients.  As MSF put it, “Funding the implementation of viral load should not be seen as a luxurious and avoidable expense, but should rather be recognized as a necessary and potentially cost-saving addition to current international commitments to scaling up treatment.”  Today, Cavidi and others have the technology to address this public health issue and provide inexpensive, near-patient HIV viral load monitoring where ever it is needed. Doing so will not only serve the patient but protect the public. All we need is the collective will to make it happen. One more reason why the time for HIV viral load testing is now. 


John Reisky de Dubnic



Further reading:

  • Aghokeng AF, Kouanfack C, Laurent C, Ebong E, Atem-Tambe A, Butel C, Montavon C, Mpoudi-Ngole E, Delaporte E, Peeters M: Scale-up of antiretroviral treatment in sub-Saharan Africa is accompanied by increasing HIV-1 drug resistance mutations in drug-naive patients. AIDS 2011, 25: 2183 –2188.
  • Estill J, Aubriere C, Egger M, Johnson L, Wood R, Garone D, Gsponer T, Wandeler G, Boulle A, Davies M-A, Hallett T, Keiser O: Viral load monitoring of antiretroviral therapy, cohort viral load and HIV transmission in Southern Africa: A mathematical modelling analysis. AIDS 2012, 26: 1413.
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Could RT technology help close the EID gap?

As the CEO of a life science company I am constantly amazed at the resourcefulness and tenacity of people in this field and I am very proud to be a part of it. When it comes to our area of HIV diagnostics, few issues are as compelling in this regard as the ongoing struggle to provide proper HIV diagnostics to infants often referred to as HIV early infant diagnosis or EID.

HIV positive mothers can pass the infection to their children before, during, or after birth via breast milk. Mother-to-child transmission (MTCT) of HIV-1 results in approximately 370,000 infant infections worldwide each year. 2.5 million children were living with HIV at the end of 2009, with 90% in Sub-Saharan Africa. The good news is that researchers Dr. Avy Violari and Prof. Mark Cotton have shown that if an HIV-positive infant is started on antiretroviral drugs before 12 weeks of age we can reduce mortality by 76% and disease progression by 75% compared to those who start treatment later. The problem for these infants today isn’t a matter of access to antiretroviral drugs (ARVs). It’s a matter of access to an HIV diagnostic test.

Diagnostics for adults is a fairly routine affair even in resource-limited settings, thanks to antibody testing. These types of tests are often referred to as “rapid tests” because they provide on-the-spot results. They work by measuring HIV-specific antibodies in the blood and making a yes/no determination of infection from there. They are accurate, easy to administer and inexpensive. In fact the US FDA has recently approved a do-it-yourself home test to diagnose HIV infection.

However, antibody testing doesn’t work on children under 18 months of age. That’s because up to that age the child still has its mother's antibodies in its blood and the test can’t tell if they are from the mother or the child. Therefore, in developed countries early diagnosis is made using the HIV DNA PCR assay, which can be used at six weeks of age. Access to HIV DNA PCR tests is restricted in resource-limited countries because they require centralized laboratories and specialized equipment. Additionally, DNA PCR produces false negative results for unrecognized HIV-1 subtypes or HIV-2.

The sad consequence of waiting to diagnose children is increased mortality and disease progression. In some regions of Africa the coverage rate for testing a child younger than 8 weeks from an HIV-positive mother is less than 4%. 1 out of 10 pregnant women in Sub-Saharan Africa are infected with HIV and 1 in 3 children born to these mothers will contract HIV. At 6 months of age, the probability of death after starting ART is 7.8% if the HIV-infected infant is already showing signs of immune deficiency (e.g. low CD4 count) but only 1.8% if the infant is asymptomatic. Most of those deaths will occur by the age of 12 months. In India, we see a similar situation.

To be clear, Cavidi does NOT market an EID test or any test to determine if a person is infected with HIV. Our ExaVir™ Load test is intended to monitor patients who have been diagnosed with other products. However, several enterprising researchers have realized the promise of RT technology for EID and have conducted independent EID studies using our RT-based monitoring test as an HIV EID tool. There is now a convincing body of evidence suggesting that Cavidi’s RT-technology may provide an important key to expanding access for EID in resource-limited settings. One of these studies by Dr. Sivapalasingam of New York University found that among HIV-exposed infants younger than 18 months old, the RT assay performed as well as DNA PCR. In 55% of cases the RT assay diagnosed HIV infection 6 weeks earlier than the DNA PCR assay with the added benefit of being subtype independent. To quote from the paper:

Our finding that a significant number of HIV infections are undiagnosed using DNA PCR testing at 6 weeks of age is important for several reasons. First, in resource-limited settings where access to medical care can be intermittent, accurate and early diagnosis of HIV when the child does present for care (during birth or routine immunization visits at 6 weeks) is especially critical. In a recent study conducted in Kenya, 65% of HIV-exposed infants were lost to follow-up by age 18 months, of whom 43% were lost to care by age 4 months. Therefore, if a 6-week DNA PCR test result is falsely negative, it is very likely that the child will not return for a repeat DNA PCR test or a confirmatory antibody test. An assay, such as the RT assay, that could detect infection soon after transmission occurs, such as at birth or 6 weeks, could dramatically increase the number of infected children initiated on ART."

Based on this research, I did a quick calculation on the impact an RT-based EID test could have: Assume you have 10,000 perinatally infected infants and detect all of them using an assay and start all 10,000 infants on antiretroviral therapy. Based on the 4% mortality rate reported by Violari et al., there would be 400 deaths. Based on the Sivapalasingam study, using DNA PCR alone at 6 weeks would have misdiagnosed 6,000 infants as HIV uninfected and therefore would not receive ART. In this group, there would be a total of 1,120 deaths (4% of 4,000 infants + 16% of 6,000 infants = 1,120). Therefore, using the RT assay at 6 weeks of age could lead to a 64% reduced mortality rate (720/1120) through better and earlier detection and treatment of HIV infection. Consider that HIV-1 results in approximately 370,000 new infant infections worldwide each year and you can begin to appreciate the benefits RT-technology can add.

I’d like to restate that the Cavidi ExaVir™Load test used in these studies is an HIV Viral Load monitoring test and is not approved for use as an HIV diagnostic test. However, the results of several studies indicate that the underlying RT-technology could provide several advantages over RNA-based tests and thus increase access to the test for tens of thousands of infants each year. In response to these promising studies we are currently seeking the funding required to adapt and re-label our current viral load test for possible use in EID. Your input is more than welcome on this. I’ll keep you posted on further developments.

John Reisky de Dubnic






Commentary on ”Reverse Innovation”

In his new book, reverse innovation 1, Vijay Govindarajan explores the hypothesis that innovations originating from low-income countries may provide solutions that can help in developed countries. A tail wagging the dog scenario that will likely rock the ivory tower of our western life science community. I think he is spot on.

Any time you apply constraints to innovation you come up with novel untried approaches to problems that may have not been attempted in a market without these limitations. This is classically demonstrated in 1st world health care delivery where profit is the motive because people have (had) the means to pay for good health care. As this paradigm shifts and we see 60 million Americans shut out from the US health care system (a global trend not just in the US), clearly, things must change.  

On the other end of the scale look at the low-income countries with enormous challenges in providing healthcare access to, not millions, but BILLIONS of people with a fraction of the resources and limited existing infrastructure to deliver this. If health care solutions must be approached within these constraints we need to think differently about how to approach this challenge.

When our team developed a new technology to quantify HIV viral load in patients as a way of monitoring drug effectiveness, we chose a marker that would allow the assay to be run in an environment with a reduced technology footprint, and at a lower total cost of delivery.  It also happened that this approach gave us added benefits not found in the existing technology developed for the first world.  Yes, it was a novel solution designed for heavily constrained environments AND it wound up being a better solution; it is capable of detecting all subtypes of HIV, not prone to contamination, does not require a clean room, and performs on par with the existing high-cost tests.  This technology makes HIV care more accessible to millions of patients in Africa, India, and Southeast Asia where the HIV disease burden is the highest.

Now, apply this technology to a rapidly deteriorating and under-funded HIV delivery system anywhere and you begin to see the benefits of constraint-based thinking. We see demand from New York, London and Frankfurt for our technology making it state of the art for a global health care reality; supply more care with fewer resources.

The theory of constraints is not new, Eli Glodrat wrote The Goal in 1984, where he introduced the concept of constraint analysis to optimize throughput. Isn’t that what we need more of in health care delivery today; more access (throughput) by eliminating delivery constraints? We applaud this insight from 1984 industry and welcome the Immelt and Govindarajan idea that "No longer will innovations traverse the globe in only one direction they will also flow in reverse." We believe in this shift and that technology will increasingly flow in both directions.

John Reisky de Dubnic





1 October 2009 HBR article "How GE Is Disrupting Itself" with GE's CEO Jeff Immelt pioneered the concept of reverse innovation