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.

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.

Global Triage - Food First or HIV First?

The global rise in food prices is triggering a crisis in many poorer countries. In many donor circles this has raised the question of whether money earmarked for HIV treatment and prevention should now be diverted to address food shortages as part of our HIV programs as Dr. Ramon Soto suggested at AIDS 2008.  It's got me wondering where the boundary between HIV treatment and general health and welfare issues lies.

Should it be the responsibility of organizations working against HIV to devote their funding, which doesn’t reach far enough as it is, to try and solve other societal issues they encounter in the fight against HIV? Or should it be the responsibility of other relief organizations or the local governments themselves?

In the parts of the world suffering most from HIV, organizations are already struggling to provide universal access to ARVs, viral load and CD4 monitoring as well as prevention. The money is never enough to help everyone as it is. Spreading those funds even further to include food support could undermine the progress made thus far.

 On the other hand, the food crisis is fundamentally undermining the effect of those people who do receive HIV treatment. Rising food prices are not only affecting the health of people living with HIV, it is changing the priorities and behavior of people in general. More and more individuals living with HIV are going to have to decide between buying medicine or buying food. The ones who do buy medicine at the expense of their nutrition won’t be getting the full benefit of treatment anyway since their immune systems will already be so weak.

For me, this is a real chicken and egg situation. Both sides of the argument have ugly downsides. So any solution will be the lesser of two evils I suppose. It’s determining which is the lesser that has me stumped. What do you think?

THE DONOR DILEMMA

Millions of lives have been saved thanks to the generous donations of people and organizations around the world to fight HIV. Their efforts are making a difference in the war on HIV and AIDS.  Sadly, according to a recent report by the Center for Global Development, (CGD) many of these well-intentioned organizations are inadvertently undermining the very healthcare systems they are trying to aid.

The study focused on HIV initiatives in Mozambique, Uganda and Zambia. It reveals that in those three countries, because of the process requirements that come with the money; the programs initiated by major donors create a burden on already shaky healthcare infrastructures.

By specifying how the treatment is to be administered, the fund provider creates a treatment process for HIV that is separate from the rest of the healthcare system. Having another separate process to learn and run creates new complexity and burdens on already over-burdened systems.

Then there are the staffing issues. Instead of adding new workers for the HIV programs, they usually train existing staff in HIV/AIDS treatment and give them extra money for doing so. Since workers in the AIDS programs get paid more, it draws health and administrative workers away from other (generally already under-staffed) areas.

According to the report all this strengthens the nation’s ability to treat HIV, but weakens its overall ability to treat all other health issues — which are numerous.

I think the report did a good job at documenting the problem, but I was disappointed that it did not investigate or suggest a solution. It would be easy to conclude from the study that perhaps the money should just be handed over to the local health ministry.

The reason many HIV fund providers no longer do that is because they tried that approach and found it didn’t work. Other donors who support a sector approach through ministries get so bogged down with bureaucracy and politics that in many cases nothing happened and if it did, it simply took too long.

Generally, the American donor organizations favor the approach outlined in the report, although many do actually give directly to ministries as well. This results in fast action, but as the report says, can create other obstacles, i.e. sustainability issues and shortage of workforce in other areas.

One thing the CGD paper did not mention is the effort that donors are making to shore up local healthcare infrastructures. I think it’s important to mention that most donors do realize these problems exist and are trying to improve the situation. The World Bank used a whopping 40% of its HIV money for bolstering local infrastructures, and the new PEPFAR plan includes a program to train 140,000 health care workers.

Science recently addressed many of these issues in an investigation of how HIV funding is being used titled ‘HIV/AIDS: Follow the Money.’ In the feature, they call for the whole system to be re-thought and point out that many are questioning if all this money for HIV is only made possible by sacrificing treatment for other diseases.

The article also points out that many countries with poor infrastructures miss out on funding because donors realize much of the money will go to waste if they give it to them. The major contributors will not give more money to a country if they feel that country cannot handle it.  In most countries, that maximum capacity doesn’t provide enough money to treat everyone. So simply going around local health infrastructures is clearly not the way to make universal access a reality.

HIV is a long-term problem and clearly the current way of doing things is a short-term solution.  It’s fantastic that these programs have saved so many lives. It’s a shame the only way they can achieve these results is by circumnavigating the health ministries.  The bottom line is that millions are in need right now and they cannot afford to wait for efficient health care systems to develop. But develop they must. 

It is not the donors’ responsibility, but that of the governments who run the health ministries.

AIDS slang speaks volumes

You can learn a lot about the perception of HIV by looking at the words people use to talk about it. I’ve just found this list of HIV slang from plusnews.org.  The terms come from some of the African countries hardest hit by the HIV pandemic.

The outlook for a person who contracts HIV in Africa is improving, but as these terms reveal the perception on the streets is rather bleak. Many of the slang phrases are also quite clever, like ‘Five and three’ (because eight sounds like AIDS). Let us know if you have any terms to add to the list and we’ll pass them on to plusnews.  

Angola (Portuguese)
Pisar pisar na min - Contracting HIV is like having "stepped on a landmine"
Bichinho - "Little bug" (the virus)

Kenya (Kikuyu, spoken mainly in central Kenya)
kagunyo - "The worm" (euphemism for HIV)

Nigeria (Hausa, spoken mainly in the north)
Kabari Salama aalaiku - Literally translates as "Excuse me, grave" (reference to AIDS)
Tewo Zamani - Translates as the “sickness of this generation” (another reference to AIDS)

Nigeria (Igbo, spoken mainly in the east)
Ato nai ise - "Five and three" (5 + 3 = 8, and "eight" sounds like "AIDS")
Oria Obiri na aja ocha - "Sickness that ends in death" (euphemism for AIDS)

Nigeria (Yoruba, spoken mainly in the west)
Eedi - "Curse"
Arun ti ogbogun - "Sickness without cure"

Nigeria (Pidgin, the unofficial lingua franca)
He don carry - "He carries the virus"

Nigeria (English)
HIV - He Intends Victory (acronym of HIV and a phrase popular among born-again Christians)

South Africa (IsiXhosa and IsiZulu)
Udlala ilotto - "Playing the lotto" /ubambe ilotto - "won the lotto" (said of someone suspected of being HIV positive; Lotto is the national lottery)
Unyathele icable - Contracting HIV is like "stepping on a live wire"

South Africa (English)
House in Vereeniging - (Acronym of HIV; "bought a house in Vereeniging", a town about 50km south of Johannesburg, refers to someone suspected of being HIV positive)
Driving a "Z3"/ "having three kids"/ the "three letters" - All refer to the three letters in the HIV acronym
Tracker - If you are suspected of being HIV positive people say God is tracking you, like the popular southern African service that tracks and recovers stolen vehicles

Tanzania (KiSwahili)
amesimamia msumari - "Standing on a nail"; euphemism for being skinny, or being small enough to fit on a nail's head, referring to AIDS-related weight loss
kukanyaga miwaya - Contracting HIV is like "stepping on a live wire"
mdudu - "The bug" (refers to HIV)

Uganda (English)
Slim - Euphemism for HIV/AIDS as a result of the associated weight loss; less popular since the advent of ARVs

Uganda (Luganda, spoken mainly in the central region)
Okugwa mubatemu - You have been waylaid by thugs (contracted HIV)

Zambia (Nyanja, spoken mainly in the east and the capital, Lusaka)
Kanayaka - "It has lit up" (refers to a positive reaction from an HIV test)
Ka-onde-onde - "Thing that makes you thinner and thinner" (HIV)

Zambia (Bemba, spoken mainly in the north and Lusaka)
Bamalwele ya akashishi - "Those that suffer from the germ" (HIV-positive people)
Kaleza - "Razor blade" (Refers to a person being thin as a result of AIDS-related weight loss)

Zimbabwe (Shona)
Ari pachirongwa - "He/she is on a (treatment) programme"
Akarohwa nematsoti - "He/she has been beaten by thieves"
Mukondas - Abbreviation of "mukondombera" (epidemic)
Ari kumwa mangai - "He/she is drinking mangai" (mangai is boiled corn seeds, which represent antiretroviral (ARV) drugs)
Akabatwa - "He/she was caught" (received a positive diagnosis)
Zvirwere zvemazuvano - "The current diseases" (the HIV epidemic)
Akatsika banana - "He/she has stepped on a banana and slipped" (someone who has tested positive and therefore will "fall" or die as a result)
Shuramatongo - "A bad omen for relatives"

Zimbabwe (English)
Red card - Like a football player being sent off, life is over
Go slow - Taken to mean that he/she is now progressing slowly towards death
TB2 - Refers to high rates of HIV and TB co-infection (used to denote AIDS)
RVR - Slang for ARVs, adapted from Mitsubishi's RVR sports utility vehicle
John the Baptist - When someone has TB or HIV, he/she is said to have been baptised by "John the Baptist", who has come to announce the coming of AIDS
FTT - "Failure to thrive" (adapted from the medical phrase, now used to describe HIV-positive children)
Boarding pass - Implies that HIV is a boarding pass to death
Departure lounge - An HIV-infected person is in the departure lounge awaiting death

Photo courtesy of General Idea, Toronto

A Taxi Ride in Lusaka

I don’t know about you, but I love talking to taxi drivers. More often than not they have an opinion and are willing to share it. They are a wealth of local knowledge, invaluable to a constantly inquisitive traveler like me. 

On one trip in Lusaka I was chatting to Chris, a local taxi driver. He was taking me from my hotel to the Swedish Embassy a short drive away. After the usual discussion about the fare, conversation turned rapidly to football. He gave the usual nonstop hysterical laughing fit at the suggestion QPR were obviously the greatest football team in the world and we soon settled down to further discussion about family and work. 

Once he knew I worked with HIV, he told me of family members who had passed away and the devastation the disease was causing. Now I know this will seem rude, but I always make a point of asking whether the taxi driver has had an HIV test or not and in Chris’s case it was no different. His answer was the same one every taxi driver I have ever spoken to in Africa has given. 

NO. 

The reasoning is this: “Since you cannot provide treatment for me, there is no point in me taking the test since I am going to die in a few years anyway. If I take the test and I am positive, I will lose my job, my friends and
possibly my family, and I will die a lonely poor man in a few years. However, if I don’t take the test, then I will not know, I will keep my job, my friends and my family, and will still die in a few years but not as lonely and not as poor.” Of course I always ask the question: “Aren’t you scared of spreading the disease?” Chris’s response was
typical – a shrug of the shoulders and a change of conversation back to football.

Thoughts on the International AIDS Conference in Mexico

I have just returned from the XVII International AIDS Conference. I always feel very optimistic after attending this event and proud to be working in the HIV field. I suppose that’s how these events are supposed to make you feel. This meeting is held every two years. The first was held in 1985. Not only is it the biggest AIDS conference in the world, but the biggest conference on a global health issue. At each conference I am overwhelmed at the amount of energy, enthusiasm and resources being focused on this disease. And every year I see the world’s resolve and commitment increasing. The number of participants in Mexico totaled 25,000 - the biggest yet. I noticed a couple of interesting developments at this year’s event.

First is a subtle shift I’ve noticed over the past few years. The meeting started as primarily a platform for doctors and scientists to share research and clinical findings. Today, that is no longer the case. In fact, there were relatively few scientific breakthroughs making headlines from the event. The meeting seems to have evolved into a platform to draw global attention to the pandemic and to the various players who are working on the problem. This year the networking and publicity aspects seem to have eclipsed the scientific aspects. And that’s OK. We have the lower-key IAS Conference on HIV Pathogenesis, Treatment and Prevention (the second biggest gathering of HIV experts) as the major platform for announcing breakthroughs in research and pooling scientific knowledge. With the level of complexity of the HIV problem, I would say both conferences serve vital purposes in the effort to overcome this disease.

Another change I noticed at this year’s conference was an increased focus on the role of diagnostics in managing HIV across the developing world. This is a natural and very welcome development arising from the increased availability of ARVs across these regions. In 2007, the efforts of organizations around the world put one million more people in the developing world on ARVs, bringing the total up to three million. With the greater prevalence of ARVs has come an increased awareness of how important monitoring is if those drugs are to do the most good for patients. Specifically, this underscores the need for a viral load testing platform, like our RT-platform, that can provide the greatest access to patients in the developing world and beyond. These sentiments were articulated by several speakers and presenters at the conference, most notably UNAIDS Executive Director Peter Piot and
President Bill Clinton. 

During one of the sessions, Peter Piot stressed the importance of proper monitoring as a vital component of success in managing HIV. President Bill Clinton also underscored this when he told of how things are changing in his foundation from a focus on supplying drugs, to expanding into providing proper diagnostics. In a keynote address he stated, “When we started our work six years ago, we focused on lowering the cost of drugs and tests needed to be in treatment…and over the years we have expanded our work to include a wider range of IRBs in diagnostics.”

The Burnet Institute, who has done so much great work in the battle against HIV, presented a poster on ExaVir Load. The Institute of Human Virology in Baltimore, Maryland added four posters of their own where ExaVir Load was used to gather viral load data. Inside our own booth, we could sense a major shift this year with more people aware of the importance of proper monitoring. We had more visitors coming by and asking us about our assay than ever before.

We have many challenges before us, but I left Mexico with a feeling that the world’s AIDS community is making progress and moving in the right direction.

To tell or not to tell?

SWISS STUDY CREATES CONTROVERSY AT AIDS 2008 IN MEXICO.
Greetings from Mexico City. One of the hottest topics  here at the International AIDS Conference is how to handle the findings of a study published in Bulletin of Swiss Medicine (Bulletin des médecins suisses) that claims, "HIV-positive individuals on effective antiretroviral therapy and without sexually transmitted infections (STIs) are sexually non-infectious.” (quoted from AidsMap)

Some experts are saying we shouldn’t talk about this to HIV patients because they will take it the wrong way and engage in riskier behavior. It is also argued that in places where access to viral load monitoring is limited or non-existent, they can’t consistently track whether or not patients have undetectable viral loads anyway, so the information is of no positive use to them. These are, admittedly, fairly compelling arguments for keeping these results quiet.

But I see three problems with that advice:

1. Patients have the right to access
Ethically, the idea of the medical community conspiring to censor legitimate scientific research because we decide people can’t handle the truth seems like a flawed idea and a dangerous precedent to set. I think all people, and particularly those infected with HIV, are entitled to full access to all the information we have on the disease.

2. No one can keep this information quiet
The genie is already out of the bottle. The fact that you are reading about this now on the Internet is proof of that.  Beyond that, the topic is being heavily debated at the world’s biggest HIV conference.  The information is published and already spreading around the globe. Nothing I know of can stop that.

3. If the findings are not delivered clearly it could misinform
The results of this study are highly prone to misinterpretation. For me this is not a justification to keep it quiet. It is all the more reason to flood the market with information to keep the findings in context.  With regard to resource-limited settings, the overwhelming majority of HIV-infected individuals have no access to their viral load or STI status to even know if they meet the criteria specified in the report.

Do I feel people should be encouraged to have unprotected sex? No. Definitely not. Given the consequences of the virus, the low risk reported by the Swiss is still something that needs to be treated seriously. Even if the statistical probability of being struck by lightning is low, I’d still discourage anyone from standing in a field with a metal rod during a thunder storm. 

As for the resource-limited setting (accounting for most of the world’s HIV-infected population) the point made in the study is mute because so few people have the level of care required to meet the criteria specified to be in the low risk category. And lets face it, the study could simply be wrong.  It wouldn’t be the first time a well-conducted study was disproved by further investigation. 

For me the issue here is not “Whether we should keep these findings from the people?” The only issue is how can we best manage the impact of this information on the population. And that means being proactive and getting the correct version of the story out to the people in the correct context from the start.