Sean Hosein, CATIE’s Science and Medicine editor, has been chronicling what’s new in HIV treatment for 25 years. (We recently reported on the 200th issue of his prime body of work, TreatmentUpdate here. Now PositiveLite.com editor Bob Leahy sits down with the ever-knowledgeable Sean (below right) once again – he first interviewed him in April 2013 - to review how our concept of HIV treatment has changed over the years and continues to evolve.
Bob Leahy: Hi Sean. Thank you for talking to us at PositiveLite.com. This is the 200th issue of TreatmentUpdate that's just been published. Now you started TreatmentUpdate way back before even CATIE was invented, didn’t you.
Sean Hosein. That’s right. I was writing about treatment initially back in 1986, in a local magazine at the time – Rites magazine – they gave me a column, half a page then a whole page. Then I started to produce a newsletter on its own and starting in 1989 and with the help of volunteers at the University of Toronto of Toronto who published and translated it for me. In 1990 when CATIE was formed, the organization helped me with stuffing envelopes, mailing it out and paying for printing etc. And after that it became a CATIE publication.
Right. So you must be very proud. This is a significant body of work. Do you regard it, Sean, as “your baby”?
Yes. Now that I have time to look back on it and now that you mention it, yes. Sometimes I still get so involved in exploring the research that is happening that I hardly have time to stand back and think about it. So thanks to you and others for reminding me!
What I wanted to explore with you is that over the course of those two hundred issues, our concept of what treatment can do has changed gradually but radically. Would you agree?
Yes. Initially we were living in a health emergency. It was about preventing people from getting AIDS, and among people who had AIDS to help them stay healthy so that they wouldn’t get a life-threatening infection.
And you were grappling too with things that might make an impact on the immune system?
That’s right. Looking back on it, it seemed at times as if everyone was grasping at straws. It is hard for people today who did not live through the first decade of AIDS (the 1980s) to understand how desperate everyone involved was to try and makes sense of this strange and new syndrome and what they would do to treat it. Nothing was off the table. There weren’t good enough tests or enough understanding of AIDS to figure out what kind of infection you were going to get next. Doctors and nurses were trying unusual combinations of antibiotics in an attempt to save people, for instance. I was writing about emerging infection fighters and things like that. Yet for many of us involved in some way in the opening saga of the AIDS epidemic it meant that we were living on the cutting edge of everything.
And that must have more or less continued right through to 1995-96 when people finally started to go on protease inhibitors. That changed prospects radically, didn’t it.
Well before 1996 there was always news about this treatment or that treatment or that immune booster or . . . and they might have had good effects initially but within six months to a year the therapy would fail. But in 1996, they introduced protease inhibitors which were extremely powerful and for the first time people were living really well and their CD4 counts were climbing to heights they hadn’t seen in years. And for the first time we saw people who had gone in to hospital wards to die, get up and walk out on their own. And they had gained weight too! Never before in the terrible history of AIDS had this happened.
That was the Lazarus effect we sometimes refer to.
Exactly. It was shocking. The first time I saw it happen, I thought “this is unusual.” Then I saw it again and again and it happened so many times that I knew this was real and that it would last. Something had changed the treatment landscape tremendously.
I remember initially we were very focussed on improving CD4 counts. At what stage did the realization that we could measure viral load and understand the need to get that number down happen?
That emerged from the clinical trials of the drugs at the time. The first viral load test that I knew about could only count down to about 10,000 copies. That was in 1995. Then the next generation of tests came that could count down to 1,000 copies and then 400 copies. And in the late 90s we had tests that could count down to 40 or 50 copies. So as these tests became more and more accurate and the drugs more and more powerful, doctors realized that to keep the amount of virus in the blood as low as possible was really, really important.
And at some point we realized that the amount of virus in your blood also had an impact on your ability to transmit the virus. That was an additional component of treatment. When did we start to think like that? Remind me.
The researchers started to talk about this around 2000 and there were isolated studies that suggested there might be an impact. But it wasn’t until HPTN 052 which came out almost three years ago that there was definitive evidence among heterosexual discordant couples that if you give the positive partner HIV treatment, it reduces the virus in the blood and likely in the genital secretions so the chances of passing on the virus fall tremendously. There have been various studies done in the real world – in South Africa and China – and you see that the numbers of new infections fall, but it never falls 100%. It has fallen by 30% in some places because maybe people didn’t take their meds, or maybe the medicines were too toxic because they were the first generation of meds. In other places new infections have fallen by nearly 50%. But in these “real world” studies we have not seen the 96% reduction that was observed in the well-controlled trial, HPTN052.
So I guess out of all that, discussions started to occur about whether as an individual strategy getting your viral load down was an effective prevention strategy to control HIV transmission.
Yes. People at the WHO - the World Health Organization – and UNAIDS and, in Canada, Dr. Julio Montaner at the BC Centre for Excellence in HIV/AIDS began to talk about treatment as prevention and the promise that it held.
So prior to that point, treatment had been regarded as an individual issue but we started to think of the impact of treatment on population health, of community health.
Yes they started to think treatment could reduce the spread of HIV.
This was a huge step in the evolution of treatment, then ,from something that was about just improving your health, improving your immune system, improving your lifespan, to something that could get the health of the community in better shape.
It was a huge step. In the absence of a vaccine, they started to look at treatment as prevention as one way of reducing the risk of transmission. I would say that treatment as prevention does work. It may not work at the level of 100%, as we would like it to, but many studies around the world are showing that it has some effect. In places like British Columbia where the BC Centre for Excellence in HIV/AIDS has been a pioneer in using treatment as prevention, it showed that among heterosexuals and among drug users the spread of HIV has slowed down in conjunction with more widespread use of ART. However, there has not been as significant a decline in transmission between gay and bisexual men in BC. So I would say it works – it may not work at 100%, but does any intervention ever work 100%? It’s making tremendous progress.
And I think most people make the point that it doesn’t mean the end of condoms – people who are negative in particular will not be able to abandon the use of condoms until the virus has gone. Treatment as prevention is just another strategy, would you agree?
We will always need condoms for a number of reasons. I would also caution that there are a lot of STIs out there and that we’ve seen the spread of Hepatitis C through condomless anal intercourse among HIV-positive people, particularly gay men.
So you’ve made the case for treatment as prevention for people who are not on treatment but perhaps are considering going on treatment but you’ve also written recently about why some people don’t want to start treatment. It almost seems illogical until you think about the human side of treatment decisions and how important a decision it can be. Maybe you could recap for readers what those reasons might be.
Yes, let’s talk about that Bob. I would say that nobody should start treatment until they are ready to, psychologically even and I think that especially these days when they are encouraging frequent testing of people at risk, more people are going to find out that they are HIV-positive earlier in the course of the disease. They may not be psychologically prepared for it. And so I think it’s perfectly legitimate for someone to say “I’m not ready to start treatment right now”. That’s fine, but in the meantime you need to think about what treatment can do for you and how beneficial it is.It may be that some people haven’t had a chance to have that fully explained to them and have had to grapple with that.
To be fair, starting treatment is a big step for people and they need a bit of time. But they also need to know that starting treatment today is generally very simple, like one pill once a day. If you are starting treatment today the chances of getting side effects are much, much lower than they were 15-20 years ago.
Right. Before we go into why treatment might work well for them I just wanted to explore a little more where that hesitation might come from and I think you mentioned in your article three things. One – side effects; two – too many pills, the pill burden and three – fitting it in their lives, scheduling issues. These are the sort of things that stop people jumping right in. Is that correct?
Yes.
I have to say, Sean, that those reasons don’t strike me as representing very big barriers to taking life-saving drugs. One pill a day doesn’t strike me as much of a pill burden. It takes ten seconds and that surely shouldn’t present a scheduling problem, finding time in one’s day. Side effects are, as you’ve said, quite often minimal or non-existent. I guess what I’m saying is that these things could be talked through with their doctor – because, to be honest, those arguments, if you weigh them against potential benefits – are not strong.
I agree those arguments are not strong. If people raise them it’s because the average person who hasn’t been involved in treatment may not know about the current state of the art, how much easier it is to start treatment these days. However the main reason in the study that people didn’t want to start treatment is that people were saying “my body is telling me that my body is not ready for it.”
And that’s valid. Factor in the psychological implications of being diagnosed with HIV, which I think are very important, and now you are getting in to the meat of why people may not be ready. It’s an emotional response. Would you agree?
What we need are smaller focus groups to tease out the meaning of things like “well, what do you mean by your body is not ready?” Or what do you mean by ”Well I don’t have symptoms so I don’t see why I should begin taking it”.
Yes, but that’s a knowledge thing. If you explain what inflammation is about, for instance, and the damage it can do to you that you may not see, surely we can address that?
Oh, it can be addressed. But I’m just saying that right now you and I are imagining what people might be thinking, and we are probably on the right track, but let’s have several focus groups that involve newly diagnosed people and find out what they are thinking, perhaps not understanding that once you’ve got HIV it’s really best to start treatment right away.
I think I agree with you Sean. I think that was the intent of your article, that it was saying we do have a little bit of a problem, there is some more work our community has to do in terms of education, in terms of understanding the rationale of newly diagnosed people, so that we can give them a better shake at getting healthy.
Yes, I think that for people who find out they are newly HIV-positive, it’s mostly a shock, it’s mostly unexpected, and if you aren’t immersed in treatment like you are and say “look, that’s not a good argument” then it’s different. People need a chance to process their diagnosis. And you know after we talk to people, after counselling and explaining to people the benefits of early treatment and why it’s good to start, then most people do start. Or fairly soon after.
I must confess Sean I’m an advocate of starting treatment early, as you probably know, but the piece that has always concerned me and still concerns me is this education piece and the difficulty in getting true informed consent, when someone is a little bit vulnerable, where their knowledge level coming in is almost certainly low to zero. So that’s the piece that strikes me where we need to make sure we do the work so that if people are offered treatment early, it’s a well-based decision that they make. I just feel that if I were placed in that position now as a newly diagnosed person, not knowing much about HIV, I could be very easily influenced, if a doctor suggested that starting me on treatment right away was a good thing. I think people are very vulnerable at this place in their HIV journey and we have to make sure that they are protected as much as possible.
Yes, and I’m not in favour of somebody rushing in on treatment within a few weeks of learning that they are positive. There should be discussions that educate people about the state of HIV today but certainly it shouldn’t be the case that you get a positive test result and immediately it’s “here, take some pills.” No one involved in education and fighting the epidemic means that.
I think you and I are on the same page on this one, Sean. Now let’s go more in to the case for people starting treatment early, because we’ve talked a lot about why they might not, but what’s the counter-argument? What’s the case for starting treatment early? How strong is it? Let’s talk both from a prevention point of view and with respect to health outcomes too.
There are a lot of arguments for starting treatment early. It keeps the level of virus as low as possible, HIV causes inflammation which damages many organs and paves the road for bone disease, heart disease – things like that. The sooner you can suppress this viral replication, the better. Also early treatment helps your immune system and you need a healthy immune system.
You didn’t mention the possibility of making someone a less infectious person?
And so another benefit is for the community. It makes people less sexually infectious or, if you are using needles, less likely to transmit the virus. And that’s a good thing for your partner or partners and it’s a good thing for society. You know there is only so much money in the health budget and we all have a role to play (and a say) in how our scarce health dollars are spent and over the long-term.
OK, can we loop back then to the case against early treatment for a minute? I know when Dr. Colin Kovacs from Toronto’s Maple Leaf Medical Clinic spoke at the OHTN Research Conference about early treatment he spent some time talking about the potential for side effects to emerge in the long term and whether that in itself was cause for delaying the start of treatment.
I think it is part of the discussion when the offer of treatment is made. Everything you take has the potential for side effects whether it’s a herb or a medicine or tea. Now with the HIV drugs used to start treatment today, they are very safe and for the most part . . . people have been taking them for quite a few years and the effects are well known. So I think that there is generally a good handle on what you can expect. And when your body is in relatively good shape as it is early in the course of HIV disease if you start taking medicines then you tend generally not to get serious side effects.
Dr Kovacs’ bottom line - I hope I’m stating it correctly - was that it’s probably best to stop the inflammation process as early as possible, so his inclination is to recommend that people start treatment early.
My suggestion is that people consider starting treatment early and have that conversation with their doctor. It’s about stopping inflammation and I agree with Colin. With inflammation we are finding more and more that it does really bad things to the heart, lungs and the bones . . .
So we have a fairly persuasive case for starting early, and we have those arguments we discussed earlier for not starting treatment yet, are we doing enough to make sure that people understand that yes, there are pros and there are cons and what is the balance of those pros and cons?
We won’t know until we ask people about that. What I can tell from British Columbia, where there is good data on this, and certainly from San Francisco, is that people are starting treatment earlier, so I think the case is being made. I think the area we also need more work on is encouraging people to practice safer sex, whether they are negative or positive. Also people who perceive themselves as negative need to get tested; about 25% of positive people in Canada don’t know they are positive.
OK we have had a good discussion about when to start treatment, etc. I just wanted to discuss how all this ties in to treatment as prevention.You’ve made the case for moving toward earlier treatment. I would say that the HIV community, at least in Ontario, has so far been less than enthusiastic in embracing this as a prevention strategy. Do you think that’s a problem?
I think it’s fine to have that contrary point of view because it is, in part, rooted in the history of AIDS. I mean in the 80s and first half of the 90s when people were encouraged to start treatment early, sometimes treatment had very clear, horrible side effects, like nerve damage that would come from ddI (Videx) or d4T (Zerit) and so on. . . And in the mid-to-late 90s we had repeated things going like lipodystrophy, which is very distressing. That background knowledge causes worry at some level, whether it’s subconscious or up front. So I think many people are coming at this from a historical perspective. They may not be aware they are. It is perfectly reasonable to be cautious. But then, as we said, treatments today are a lot better and we are not getting those sorts of problems.
I have bad neuropathy in my feet caused by meds and I can relate. So I can recognize the dangers of jumping in too early but at the same time I recognize that things have changed a lot. It strikes me too though that when we talk about the opposition to treatment as prevention, we are in a bit of a transitional phase where . . I think I’m an example where I’ve switched sides from someone who voiced real concerns to someone who has reassessed their position. I sense we are at a place now wherer other people may be making similar decisions, or perhaps waiting to see more evidence, waiting for the situation regarding its efficacy in gay men to become clearer. But I do sense we are at an important place in our history where, certainly in Ontario, we are taking stock of where we should go next.
Yes, I think we are, Bob. That’s a good way of putting it. You know, treatment as prevention is being taken up in China, France, Panama, and other places and those are just some of the big ones, and I think it’s the way the whole word is gradually moving. BC has managed to do it and I hope that eventually other parts of Canada will take it up. But remember that while this is happening, we also have to have more opportunities to offer HIV tests, and there are competing priorities for the health care system.
Meanwhile we see a move to normalize HIV which of course has funding implications.
And the key thing here is that HIV is not happening in isolation. We are moving towards the concept of a healthier society where we try to prevent diseases happening. HIV is just one part of it. But many people are moving towards treatment as prevention for a whole bunch of reasons. We need to keep public interest in funding HIV treatment and making it freely available. Treatment as prevention is something that the public can understand and policy makers can understand. It’s in the interests of HIV-positive people to make treatment as prevention succeed.
Right. Isn’t it interesting, Sean, how we started off here talking about the early days of TreatmentUpdate and how frantic we were then to try and find things to stave off infection and now we are talking about how HIV treatment has evolved in to a huge global health issue. That evolution we’ve seen is fascinating to me. I think this discussion has been really good.
Sean: I do too.
Bob: Thank you very much, Sean. You’ve been amazing!