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

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. 

A solution hiding right under our noses

Viral load monitoring shown to be an effective way to boost compliance in HIV patients 

Even when ARVs are available, patient compliance has always been a problem. Some programs go to the extreme of having a nurse supervise every dose, every day. The reason it’s such a big deal is that even missing a few doses gives HIV the chance to adapt to the medication and develop resistance. Treatment options are limited and expensive, especially in developing countries.  

So why are patients putting their own lives at risk by skipping doses?
Sometimes it’s a money issue. Sometimes it’s a lack of knowledge about the drugs and their disease. Sometimes it’s because of the side effects. But in the end, we don’t know what they do when they take the drugs and go home. When their doctors inquire about their compliance, they often just say what the doctor wants to hear. Which makes it difficult to know before it’s too late which patients need extra help to consistently take their ARVs.  

A recent study from Doctors Without Borders has shown that viral load monitoring may be the solution. A group of HIV patients in Thailand were put on monitoring for the first time. Many of them showed detectable viral loads. Most of these were linked to poor compliance.   

By monitoring viral load, doctors were able to see quite early which patients were not responding well to treatment. With this knowledge they could single them out for counseling early on in their treatment regimen. Moreover, the patients’ viral load could be used as a tool to educate and motivate the patient during counseling.    

Virtually all of the patients who were given extra counseling in this manner saw their viral load drop to undetectable levels indicating better compliance. The few who didn’t were flagged as non-responsive and put on second line treatment. This reduced the chance of drug resistant strains developing and being passed on, and avoided wasting valuable drugs that were no longer effective for those patients. 

In an ideal world, patients would follow their doctor’s instructions to the letter and they’d be honest about everything to do with their treatment. But that’s not the world we live in. In the interest of public health, for both individuals and populations as a whole, we should explore these potential solutions to nagging problems wherever we find them. Especially when it is as easily addressed as this issue is. 

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.