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.” 

                          

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

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

CEO

Cavidi

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.
• Hamers RL, Wallis CL, Kityo C, Siwale M, Mandaliya K, Conradie F, Botes ME, Wellington M, Osibogun A, Sigaloff KCE, Nankya I, Schuurman R, Wit FW, Stevens WS, van Vugt M, de Wit TFR: HIV-1 drug resistance in antiretroviralnaive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study. Lancet Infect Dis 2011, 11: 750 –759.
• Lynen L, Van Griensven J, Elliott J: Monitoring for treatment failure in patients on first-line antiretroviral treatment in resource-constrained settings. Curr Opin HIV AIDS 2010, 5: 1–5.
• Médecins Sans Frontières: Undetectable – How Viral Load Monitoring Can Improve HIV Treatment in Developing Countries, July 2012
• Murtagh M: UNITAID HIV/AIDS Diagnostic Landscape 2nd Edition. 2012.
• Quinn T, Wawer M, Sewankambo N: Viral Load and Heterosexual Transmission of Human Immunodeficiency Virus Type 1. N Engl J Med 2000, 342: 921–929.

Testing viral load just once a year could change the face of HIV

Despite great strides in increasing access to antiretroviral drugs in resource-limited settings, access to viral load monitoring continues to lag behind. The general consensus seems to be that it would be great to have, but with drugs in hand, patients can make do without. A new study has revealed just how extensively this lack of viral load monitoring is undermining treatment.

The study, which monitored 2,333 patients across the Asia-Pacific region, found that patients were 35% more likely to develop severe HIV related illnesses, or die, when viral load monitoring was performed less than once a year. Given that the majority of the world’s 33+ million HIV positive patients live in similar resource scarce settings, that adds up to millions of preventable fatalities. The study also found that, in these settings, monitoring viral load multiple times throughout the year did not significantly alter the effect of treatment, so one annual test is enough to improve a patient’s long term outlook.

Viral load tests not only let healthcare workers see if a treatment regimen is effective, it allows them to monitor adherence to the regimen – a frequent a problem and often the cause of spikes in viral load. Monitoring otherwise provides vital information in determining when certain drugs are no longer working and need to be switched. This is both to find a treatment that more effectively suppresses the virus and to prevent the development and passing on of resistant strains of HIV.

A visualzation of viral load levels. Image from www.gileadhbv.com

 But the test remains uncommon in resource-limited settings, primarily because traditional test kits are expensive and demanding of both laboratories and the people running them. It is also not a priority because, in many cases, even if a treatment regimen is discovered to be failing, there are no other options available to switch to. 

The focus going forward needs to be, beyond providing 2nd and 3rd line treatment options, providing viral load solutions tailored to the resource-limited setting so the drugs can be used effectively and drug resistance limited. As the study revealed that only one test a year is required to see 35% fewer cases of sever illness and death, hopefully mindsets about the feasibility of scaling up access to viral load monitoring will start changing.

For more details about the study, check out the story on AidsMap. 

The HIV Subtype Picture

If you live in the West, you might be a little surprised by the subhead on this map. In Western countries, we’re used to it being a given that subtype B is the most prevalent strain of HIV. This map is a great visualization of where the HIV epidemic actually stands in terms of subtype distribution and concentration.

It also makes it clear why there is such a great need for a subtype-independent viral load monitoring assay like our ExaVir Load. It’s not only because the traditional assays were developed for measuring subtype-B and are of limited use outside the Western world, but because the spread of that huge prevalence of other subtypes Westward is only a matter of time.

 

As far as our ExaVir Load’s performance goes, that whole map might as well be the same color. But with the diagnostics most prevalently in use today, we’re facing a problem in providing accurate disease monitoring. And the problem will only get bigger as subtypes continue to migrate and mix. 

This is why we’re continually developing diagnostics that are subtype-independent and why we believe it’s so important. We have every opportunity to be ready for when the need for such diagnostics can no longer be ignored, so let’s stay a step ahead this time. 

Watch How HIV Works

Do you know what Reverse Transcriptase (RT) is? For one thing, measuring it is what makes our ExaVir HIV viral load test unique. But unless you have a medical background, it’s hard to get your head around RT. That’s why I’m so happy someone sent me this YouTube video. It’s a bit thick on technical-speak but the animation is fantastic and the role of RT very well depicted.

RT is the perfect marker for measuring HIV viral load because a retrovirus, like HIV, requires a functional RT in order to be infectious. This means that by measuring RT activity we can accurately measure viral load regardless of subtype. If you have any other videos related to RT or HIV viral load please let me know.

Universal Action Now

The biggest health conference in the world is fast approaching! On August 3rd the foremost HIV experts from around the world will gather in Mexico City for AIDS 2008. The participants will total over 25,000 along with 3,000 from the international media. So you could definitely say the world will be watching.

The key to progress is sharing our insights and achievements, and AIDS 2008 is the biggest meeting ground for the minds working to fight HIV to present their work and pool their collective intelligence. Quite possibly the most important aspect of the conference is identifying where we have come up short in our response to HIV, and what we need to do about it to move forward.

The theme of this year’s conference is Universal Action Now. It’s a vital rallying cry and reminder that even though we’ve made a lot of progress in fighting the HIV pandemic, we must maintain as much a sense of urgency as ever if we are really going to beat it. AIDS 2008 will seek to accomplish this through fully opening up dialogue, not only in person at the conference but by utilizing the web, creating networks and establishing communication that goes far beyond the five days of the event itself.

The conference will also mark the first time an international AIDS conference has been held in Latin America. This will help highlight the growing HIV problem in this area and others that are often overlooked due to the massive scale of the HIV problem elsewhere. With the lessons that we learned the hard way in places like Africa, we have a great opportunity to stem the tide of HIV in countries where the infection rate is still relatively low. But only if we take universal action right now.

The three biggest myths about viral load monitoring in resource-limited settings

Through my work I’ve understood that there are many different perspectives on viral load monitoring (VLM). All of them are understandably products of their environment. Many of the beliefs people have regarding viral load monitoring were formed over a decade ago when there were only RNA-based HIV viral load testing platforms available.  In 2002 a new platform based on reverse transcriptase (RT) was introduced that made viral load monitoring more accessible without sacrificing reliability.

To those of you who are familiar with both platforms these myths may sound quite out of step with the times. But these opinions are widely held in many parts of the world, particularly in those parts of the world defined as resource-limited.

1. You don’t need viral load monitoring when you have CD4 testing
   HIV viral load tests and CD4 tests measure different things (see: What’s the difference between HIV viral load tests and CD4 tests). CD4 is an excellent test to see what condition the immune system is in. Viral load, on the other hand, detects how active the HIV virus is. Both these pieces of information are important for doctors to use when managing HIV.  That’s why in most developed nations, both tests are given as a routine part of HIV management.
2. Viral load monitoring is too expensive
   This was the impression made when viral load testing was introduced into Sub-Saharan Africa in the 1990’s.  The costs of the tests and equipment have come down significantly since then but the perception remains.  What people often fail to consider is the cost of not testing. A recent study(1) has suggested that frequent viral load and CD4 monitoring has the potential not only to add three quality-adjusted life years to patients’ lives, but save billions of dollars for struggling economies in Africa and elsewhere.
3. Viral load monitoring is impractical for resource-limited regions
   RNA-based platforms introduced in the 1990’s required delicate instruments and advanced laboratory conditions that are rare to find in resource limited settings. That all changed in 2002 when tests using reverse transcriptase (RT) as a marker where introduced. Today there is a test that can work in the resource limited settings but in many instances this perception remains an obstacle.

1. Vijayaraghavan A et al. Cost effectiveness of alternative strategies for initiating and monitoring highly active antiretroviral therapy in the developing world. Journal of Acquired Immune Deficiency Syndrome. 2007 Sept 1;46(1):91-100.

The difference between HIV viral load and CD4 tests

CD4 and viral load are two of the key tests doctors use to manage HIV. But the tests themselves, what they measure, and how doctors use them are quite different. Below is a brief overview of how the two tests work.

CD4 tests measure the number of CD4 T-cells in the blood to gauge the strength of the immune system in the presence of HIV infection. CD4 is an excellent test in this respect and has been the primary indicator doctors have used to monitor the overall condition of the patient’s immune system. It is most useful in determining when an untreated patient needs to begin taking ARVs. The test is usually simple to perform and relatively cheap to administer which has lead to its widespread use.

The test has two main limitations with regard to HIV management. First, there are many factors, other than HIV activity, that can affect the amount of CD4 T-cells present in the blood at any given time. So the doctor cannot be sure if the CD4 value is caused by HIV activity or other factors. Second, it can take up to 6 months for HIV activity to be reflected in the CD4 count.

While CD4 measures the body’s reaction to the virus, the viral load test measures the number of virus particles in the blood directly. A low viral load indicates that HIV is not actively reproducing and that the immediate risk of disease progression is low. A high viral load means the virus is active and the infection will progress. The viral load test is a more reliable indicator of viral activity than the CD4 test and, as such, a more reliable indicator of disease progression. It is the most useful tool in determining whether or not antiretroviral drugs are working since treatment failure is first manifested by a rise in viral load. In virtually all cases, this rise in viral load occurs within a month or two of the cause of treatment failure. 

Historically, the viral load test has had one main drawback: While a mainstay of treatment in developed nations, it has been more difficult to perform in resource-limited settings. That’s because tests introduced in the mid 1990’s are developed around platforms that measure RNA. These tests are made with delicate equipment and require laboratory conditions that are uncommon in resource-limited clinics. The introduction of the world’s first viral load test that measured reverse transcriptase (RT) in 2002 changed all that. The RT platform now provides equivalent results with simple equipment and lower demands on the laboratory running the test.

Three reasons viral load monitoring matters

1. Patients. First and foremost, viral load monitoring (VLM) helps doctors manage HIV better, thus increasing the patients’ length and quality of life.  This not only makes their lives better, but that of their families as well. It also helps the community by keeping them productive and working longer.
2. Budgets. VLM helps makes the supply of ARVs go further.  Many nations have a limited supply of ARVs, so ensuring none of the drugs are wasted is a top priority. VLM is the most accurate way to detect treatment failure, and as such gives the best indication of when to stop using medication that is no longer working for a patient. It also helps determine the best time to begin treatment, so it isn’t initiated earlier than necessary.
   
3. Society. Stemming the spread of ARV resistance.  When treatment stops being effective and a patient continues taking the same ARVs, HIV can become resistant to the drugs. And if the patient passes on their infection, their resistant strain goes with it. With VLM to help detect treatment failure, the development of drug resistance can be minimized and treatment options for patients can be kept open.

Those are my top three. If you have other reasons, please feel free to share your view with a comment.