From CATIE (June 1, 2015): Study confirms starting HIV treatment early prevents illness and death
"A large, well-designed clinical trial called START has confirmed that by initiating anti-HIV therapy early—when their CD4+ cell counts are still relatively high—HIV-positive people can significantly reduce their risk of developing AIDS, other serious illnesses unrelated to AIDS or dying. According to the U.S. National Institute of Allergy and Infectious Diseases (NIAID), the results from START “support offering treatment to everyone with HIV.”
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Bob Leahy: Sean, thanks for talking with us again. I wanted to ask you first, in the last two or three years we have had several really big developments in the world of HIV. I’m talking about two research studies in the field about the risk of transmission – HPTN 052 and PARTNER – and now we have START, dealing with the benefits of very early HIV treatment. Now the first two have sometimes been called “game-changers”. Do you consider this newest one, START, a game-changer?
Sean Hosein: Yes, it’s a tremendous advance in knowledge, Bob. It’s going to affect things forever in that this will be the trial that settles any prior scientific uncertainty about the importance of starting HIV therapy as soon as possible after diagnosis. This will be remembered just like the landmark studies you mentioned. The early release of data from START will one day be seen as a very important event in the history of the HIV pandemic.
So it’s a game-changer.
Totally. Not only that, I think it’s going to have an effect long after this announcement; there are sub-studies within START that are looking at brain health, bone health, heart health and so on and they are probably going to reveal, as some other studies have, that starting treatment early protects and preserves vital organs from further deterioration. It’s going to be really big and will add further momentum to the message of starting treatment as early as possible.
And this will have important applications for all sorts of people, right? Newly diagnosed of course, but doctors and, people who work in AIDS Service Organizations, for example.
Yes, it will have an important impact on the whole range of people and agencies involved in the health and education around HIV. Doctors, nurses, clinics, pharmacists and of course, community-based organizations . . .
It’s good news to hear. Now the findings aren’t entirely unexpected though; I mean CATIE has been saying for some time that there has been mounting evidence from studies that starting treatment early results in substantial benefits. And of course some community advocates have been suggesting way before this announcement that early treatment is the way to go, even without this gold standard evidence.
Yes, what has been happening, as you point out, is that over the past few years the evidence base has slowly been building up showing that it is advantageous to starting treatment early and finally the gold standard – a large well-designed clinical trial – proved it. And so yes, there were some people ahead of the curve such as yourself and PositiveLite.com, some doctors, researchers, patient groups and so on, but let’s also acknowledge the evidence hasn’t been really, really firm until now.
There are always people who are cautious and it was reasonable to have such caution in the past few years until the release of the START results. Few people expected the size of the difference in outcomes to be so large between the two groups--those who started treatment early and those who didn’t.
Maybe this is a good time, Sean, for those not 100% familiar with START, to summarize what the research told us in a bit more detail.
Sure. START is a trial that began in April 2011. It enrolled nearly 5,000 HIV-positive adults from all over the world. At the start of the study most people had more than 500 CD4 cells, and shortly after people entered the study - they were randomly assigned to one of two interventions. Either they received immediate ART and began therapy right away or they delayed starting on it until their CD4 count had fallen below 350 cells. And an incredible effect happened. The researchers found that after three years the risk of developing AIDS-related illness or serious illness unrelated to AIDS or even dying was cut by slightly more than 50% in people who started therapy right away. In other words, people who delayed starting therapy had twice as many adverse things happen.
And that was enough to stop the study early, right? To stop START (laughs). Or not exactly?
Well, the study was transformed. What they decided after seeing the interim analysis and seeing such ground-breaking results was that people should not be delaying the start of treatment. Any participants who were delaying treatment would be told about the results and asked to consider starting treatment as soon as possible.
It would be unethical not to offer them that opportunity when the researchers who operated START became aware that the benefits of doing so were so overwhelmingly established. Now, Sean, the trial was clearly about treatment and the related health outcomes, but people are also taking treatment to help reduce the risk of transmission to their partners. That raises the question to what extent does START strengthen the case for treatment as prevention? This seems to me to add strength to that argument a lot.
START wasn’t really about prevention. But yes, there really are two benefits to starting treatment as early as possible – one is personal health and the other is that it significantly reduces the risk of passing on the virus to a partner, once the viral load is undetectable and stays there.
I’m suggesting, Sean, that if you add those two benefits together, rather than look at them in isolation, the case for early treatment is super strong. For some people too the prevention benefit is perceived as even stronger then the health benefit. Other people want to rid the virus from their bodies as much as they can, as soon as they can. It’s an emotional reaction.
Everybody is different and has different reasons for wanting to take treatment. But yes, there are so many potential benefits for starting treatment early.
I think too there are a lot of intangibles. People often feel really good about themselves, when in less than six months they have attained undetectable. We are hearing - and I can believe it - that it feels good, that it’s good for their mental health, their emotional health, they feel better about themselves. There are a lot of ripple effects we don’t always acknowledge. One thing I want to make clear though is that starting treatment early doesn’t mean they have to start the same day they are diagnosed.
Well a few months ago I was talking to some doctors, mostly from the United States, and asking them how are people responding to the offer of treatment after they had been newly diagnosed with HIV? They told me that people from all over generally don’t have a problem with starting treatment shortly after diagnosis – within a few weeks, or at most a few months, because the word has been getting out that treatment is good for you and its generally well tolerated and usually taken once daily. People between the ages of 18 and 40 generally had little concerns with starting therapy shortly after diagnosis. The group that did have some reservations was the group that were over 50 – and just some of them.
I also heard from some doctors in B.C. that some patients are starting treatment the day they are diagnosed. Some patients want to. But you have to understand, they are getting counselling with the offer of therapy, advice about adherence; there are health navigators who help them through the health care system and other safeguards. Also, for many people who begin therapy today, the latest version of the guidelines developed for the U.S. Federal Health Ministry (called the Department of Health and Human Services or simply the DHHS) recommends very effective, safe and simple modern therapies (usually once daily). All of these factors play a role in a person’s decision to start treatment early.
But there will be some people who don’t want to start right away, for various reasons. How should we support them? They still may have concerns about side effects, or whether they can be adherent. Maybe they just don’t like taking pills, putting chemicals in their body? Bear in mind too at that point they may be somewhat confused, somewhat down, somewhat overwhelmed. Is that the best time to make such an important decision, to make such a big life-commitment?
For some people it’s probably OK to wait a bit, but that’s a decision that should be made in cooperation with a doctor who has a sense of their overall health and any other medical issues that a person might have. However, it’s perfectly reasonable for someone to raise concerns like what you’ve mentioned. At this point in the doctor’s office, there should be a dialogue about what their concerns are. In this way people can be counselled, educated, and issues can be resolved. There is so much data out there to answer concerns that people might have and reassure them about the safety of modern treatment
OK, the issue of informed consent, or put another way, making sure there is no coercion at play here seems even more important now, do you think? The fact that doctors are now armed with a very strong case suggests to me that we need to be even more protective of peoples’ rights to ask questions - or even say no.
I think we always need to be protective of the principle of informed consent. For anything health-related, not just for HIV. But particularly for HIV where this a life-long therapy, people have to be ready to make a commitment for it and people may come with little knowledge of the disease when they are just diagnosed, so yes, it can be overwhelming. That’s why it’s important to stress the need for counselling, not only before and after the test results, but also prior to the offer of treatment being made.
OK so what’s next Sean? How do we make sure that all this new knowledge we’re talking about not only gets out to those who need it but also impacts the experience of every single person who enters the health care system having been diagnosed with HIV, wherever they are in Canada, because as we know there have been regional differences in the past in what they can expect. And to be honest, that has always made me uncomfortable.
We need to have a larger conversation about health care systems to understand where the next checkpoint is in HIV care as researchers strive to understand how people get hooked up to care and stay in care and on treatment with an undetectable viral load. This type of research is called Program Science and finding out what is happening within health care systems and what we can do better is important. I think research is beginning to take place partly as the treatment cascade concept gains traction.
Right, that is a bigger conversation, Sean, even though it’s closely linked to the treatment issues we’ve been talking about. Let’s save that one for another day. Thanks again, Sean for talking to us today. You’ve been great.