The HIV viral load blog

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.

Barack Obama’s ambitious HIV plan inspires hope, but hope is only the first step

“We are all sick because of AIDS - and we are all tested by this crisis. … When you go to places like Africa and you see this problem up close, you realize that it's not a question of either treatment or prevention – or even what kind of prevention – it is all of the above. … Yes, there must be more money spent on this disease. But there must also be a change in hearts and minds, in cultures and attitudes. Neither philanthropist nor scientist, neither government nor church, can solve this problem on their own - AIDS must be an all-hands-on-deck effort.”
 [Barack Obama, World AIDS Day Speech, Lake Forest, CA, 12/1/06]

Newly inaugurated US President Barack Obama has said a lot of inspiring things, not the least of which are his comments on HIV/AIDS. Everything he says is right on target, exactly what we want to hear and exactly what we want to see happen. Not only is he promising an increase in funding to USD 50 billion for the global fight against HIV and doubling the number of people on treatment, but sending out the message that being free from living in fear of the disease is equally important.

The strategy outlined and the eloquence with which it’s delivered is a startling change from what we’re used to getting from America’s administration. One of my favorite parts of the plan is that they’ll use “best practices – not ideology – to drive funding for HIV/AIDS programs.” There has been some questionable usage of funding in the past, so it’s great to hear a solid commitment to basing funding decisions on reason and science.

They’ve also outlined plans to develop ARV delivery, health care infrastructures and access to clean drinking water. Though not specifically mentioned, I hope these developments also lead to universal access to the essential diagnostics used in treating patients with HIV, such as viral load monitoring, as it’s a vital next step in improving the lives of HIV patients. 

Now we all know that what is promised during an election campaign doesn’t always end up turning into reality, but I’ve never seen the kind of hope for the future of the fight against HIV that President Obama has inspired. While I don’t believe every last thing that’s been promised will happen, I do believe that Obama’s new strategy will create a vast improvement in how the world approaches the pandemic. As the largest and most influential funder of HIV initiatives on the planet, that’s good news for a lot of people in many parts of the world. As President Obama said in the quote above, everyone is affected by AIDS.

Do your part to help the new administration deliver on the promises that have been made. The ideas and the funding are there, but it’ll take more than one man to make these changes a reality. Visit Obama’s website and check out the Events section. From there, you can organise or find HIV awareness events in your community. It’s open to people from all countries, so sign up and get out there.

Nobel Prize Gives Credit Where It’s Due…sort of

HIV has always sparked controversy – all the way back to when it was first discovered. Françoise Barré-Sinoussi and Luc A. Montagnier were recently awarded this year’s Nobel prize for their role in the discovery of the virus. More than two decades ago they identified a virus they named LAV, which later became known as HIV.

But who discovered the virus first would be disputed for many years after. A year after the French team’s discovery, Dr Robert Gallo, who was working in the States, discovered a virus he called HTLV-3 that would turn out to be the same virus. It eventually became clear the specimen the new discovery was taken from had come from the French team’s lab.

So it isn’t really disputable who discovered it first (though they gave it their best shot), but at that early stage Gallo’s research and the methods developed at his lab were instrumental in discovering HIV and propelling understanding of the virus forward. The Karolinska Institute were quoted by the New York Times saying, “Never before has science and medicine been so quick to discover, identify the origin and provide treatment for a new disease entity.”

So I say we take this moment to thank all the scientists involved in that remarkable achievement. Their effort made developing the tests, drugs and monitoring assays that now save millions of lives possible. Beyond the controversy of who deserves what that always comes with these awards, that’s all that really matters – advancing medicine and improving human lives. 

World AIDS Day 2008 – Economic crisis raises significance of this year’s event

December 1st is World AIDS Day. This year it's more important than ever. It was instituted in 1988 to spread awareness of the severity of the HIV pandemic and how much work needs to be done to stem the tide. Local governments and organisations around the world answered the call and have been doing their part to fulfil the promise of the event each year since. But this year we face a big distraction – the economy.

All around the world, organisations are slashing their budgets and consumers like you and me are looking for ways to cut back. Where will these organisations and individuals look to cut? I guess I’d be naïve not to assume that funding of HIV treatment initiatives would escape their fiscal fitness program.

If you’re in a position to provide assistance or funding to HIV-related programs (and that’s all of us), I’d ask you to consider the cost of cutting back now.

Over the past 20 years, the global HIV community has made astounding advances in battling the pandemic. Back in 1988, the percentage of people receiving treatment who needed it was negligible. Today, millions have access to ARVs, including those in developing countries. Prevention and education campaigns are reaching new audiences all the time. Real strides have also been made in developing the medication and diagnostics required for proper treatment. The investment of time and money since 1988 is paying dividends today in terms of both hampering the spread of the disease and treating those already infected.

Unfortunately, HIV doesn’t slow down during a recession. It is always striving to move forward and will take swift advantage of any weakening of resolve. If treatment is interrupted for those already on ART, their health will be compromised and an increase in drug resistance is certain. If we don’t keep the number of people on treatment rising, AIDS deaths will jump even higher than the millions it already claims annually. And if we don’t keep prevention campaigns going strong, the virus will spread even faster.

This isn’t only a humanitarian concern, but an economic one as well. These negative consequences will result in enormous financial strain on the battle against HIV in the long run. This economic crisis is not just in Africa, but in everyone’s backyard. We need to keep in mind that life will go on during, and after, the recession, and we don’t want to undermine all the work we’ve done up to this point by not looking ahead.

HIV affects everyone and has the potential to be an even greater problem than it already is, on both our health and our economy. So do your part to spread awareness on this World AIDS Day. Here are 5 things you can do to keep the fight against HIV moving in the right direction.

1.    Write a blog post about World AIDS Day, or use other social media to spread the word
2.    Write a letter to the editor or an opinion column for your newspaper
3.    Call or write your local government official and tell them you believe that fighting HIV is still a priority
4.    Get involved in local World AIDS Day events, or create one if nothing is planned in your community
5.    Wear a red ribbon and encourage others to do so

If you have any ideas of your own, please share them in the comments section.

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. 

What Sudden Spikes in HIV Viral Load Really Mean

The following was written by Professor John Mills, Monash University, Australia, who I have had the pleasure to work with for a number of years. John is an authority in the HIV field, having extensive experience both in research and in practice, including measuring viral load with our ExaVir Load assay. I’m posting this piece because it does a great job of explaining what HIV viral load blips are, when you should be worried and when it’s a false alarm.

An elevated HIV viral load on therapy: is it a "blip" or a "bust"?

 Although measurements of HIV viral load are useful for assessing the prognosis and need for treatment of patients not on anti-retroviral therapy (ART), they are absolutely critical for monitoring the efficacy of therapy. 

When treatment naïve patients are started on combination ART, the HIV viral load should fall very quickly. Usually within 2-3 months, and certainly by 3-6 months, the viral load should be "undetectable". 

What constitutes an "undetectable" viral load depends on the assay system used. It varies from less than 400 copies/ml to less than 40 copies/ml. Although it might seem that <40 is better than <400, to date the evidence suggests they are equivalent. Clearly, however, viral loads at or above 400 are a real cause for worry (Pilcher et al, 1999). 

Once a patient on ART achieves an "undetectable" viral load, it should remain undetectable indefinitely if they continue to take their ART as directed, and do not develop an unusual circumstance that would interfere with drug efficacy (e.g. drug interactions or a gastrointestinal condition interfering with drug absorption or metabolism). 

Surprisingly, a number of studies, including ones in which viral loads were measured daily (Nettles et al, 2005) – as well as substantial clinical experience – have shown that many patients will have transient elevations of viral load known as "blips." Blips are defined as transient, low-level increases in viral load. Specifically, they are a single detectable HIV viral load measurement of less than 1000 (although rare blips may be slightly higher than that), which is immediately preceded and followed by an undetectable viral load (Gallant 2007).

Argument continues as to whether blips are a laboratory artifact or represent true HIV viremia. I think the weight of evidence is that they do represent short-term viremia. 

In an individual patient, the frequency of blips seem to be related to less than perfect adherence to the treatment regimen – patients who have missed ART doses in the week prior to the blip are more likely to have them than patients who are highly adherent (Podsadecki et al, 2007). Curiously, however, blips do not seem to predict subsequent development of an HIV strain resistant to ART ("virologic failure" of the ART regimen). 

How can you tell if a patient who previously has had an undetectable viral load has just a "blip", or whether it is a "bust" – an elevated viral load likely indicating that the ART regimen is failing (due to resistance, poor adherence, poor absorption or drug interactions)? 

If the renegade viral load is well above 1000, it is almost certainly a "bust." But the only way to definitively answer the "Blip or Bust" question is to perform another viral load assay, ideally 3-8 weeks later than the first. Even if the first value is well above 1000, it could still represent a lab error and should be repeated (you wouldn't want to switch a patient to a second line regimen on the basis of an erroneous viral load!). 

If the first viral load value is >1000, and the second value is also >1000, and especially if it is higher than the first, it is almost certainly a "bust", and the patient should be investigated for ART regimen failure. 

If the first value is <1000, and the second value is back to undetectable, you can relax as you're seeing a blip.  However, since blips are related to episodic lapses of adherence, it is definitely worth reminding the patient that the best results from ART are achieved if 100% of doses are taken. 

References

Gallant JE (2007).  Making sense of blips.  J Infect Dis, 196:1729-31

Nettles RE, Kieffer TL, Kwon P, et al. (2005). Intermittent HIV-1 viremia (blips) and drug resistance in patients receiving HAART.  JAMA 293: 817-829.

Pilcher CD, Miller WC, Beatty ZA, Eron JJ. (1999).  Detectable HIV-1 RNA at levels below auntifiable limits by Amplicor HIV Monitor is associated with virologic relapse on antiretroviral therapy.  AIDS 13:1337-42.

Podsadecki TJ, Vrijens BC, Tousset EP et al. (2007). Decreased adherence to antiretroviral therapy observed prior to transient human immunodeficiency virus type 1 viremia.  J Infect Dis 196:1773-8. 

The Answers to Your HIV Viral Load Questions

The people at The Body have put together this pretty comprehensive resource of information about HIV viral load and what it means to patients. They do a good job of addressing the questions that patients may be worried or confused about, like sudden spikes in viral load and signs of drug resistance. The Body is a great HIV info resource in general, not a bad page to keep in your bookmarks.

A Viral Load Monitoring Success Story from Zambia

I’ve heard a lot of great stories about how viral load monitoring has helped doctors in resource-limited settings. One in particular always jumps to mind. A Dutch physician named Dr. Piet van Hasselt was working at the Kara Clinic in Lusaka, Zambia when he decided to give viral load testing a try to see if it made a significant difference in his treatment practice.

Up until that point, he only had access to CD4 tests. For his trial, he tested 40 patients with low CD4 counts. He intended to switch them to second-line therapy, assuming their treatment was no longer effective. The viral load tests showed that 60% of them had undetectable viral loads, and as such could remain on first-line treatment.

This gave the patients more time on effective therapy and kept more treatment options open in the future. It also saved the clinic a lot of money as second-line therapy is many times more expensive than first line – money which could then be used to provide more patients with treatment.

These are the kinds of results I believe all clinics should be entitled to and why I push for universal accessibility to viral load monitoring. When you look at stories like this, the medical and financial implications of universal accessibility are staggering.

Jan-Olof Morfeldt in Memoriam

It is with great sadness that I learned of the recent death of Jan Olof Morfeldt. Jan Olof, an HIV doctor, started Noaks Ark (Noah's Ark) back in 1985 along with a number of colleagues. The organization has been an outstanding combatant in the fight to try and stop the spread of HIV in Sweden and continues to provide much needed assistance to those already infected.

Jan Olof was passionate, compassionate and an inspiration. His enthusiasm and great sense of humor will be sorely missed. Our thoughts are with his family, friends, colleagues at Noaks Ark and the many that he has brought help and hope to throughout the years.

Photo: Elisabeth Ohlson Wallin

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.