Role of the AntiRetroviral Therapy: Management of non-infectious co-morbidities in HIV-infected persons
Q&A with Jens D. Lundgren
Professor of Viral Diseases at University of Copenhagen, Faculty of Health Sciences
Rigshospitalet, Copenhagen, Denmark
Copenhagen HIV Programme
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By Andrea Massa
Professor, what’s the state of the play of anti-retroviral therapy for HIV patients, particularly here in Europe?
Hopefully, the idea in Europe at the moment is that we need to make sure that people are initiated before they develop severe immune deficiency.
You are a co-PI on the START study (Strategic Timing of AntiRetroviral Therapy). What sort of indications are coming from this trial? What’s your view about the timing for antiretroviral therapy?
The START study is trying to address whether we should hit hard and hit early. We are not done with the trial yet, so until such time we don’t know whether it is a good idea to hit hard and hit early. The point is that the current guidelines are aimed to initiate therapy before people are risk of AIDS defining events. The only reason to start therapy earlier would be because treatment is postulated to prevent end organ disease, cardiovascular disease, renal disease, etc. We don’t know, we have a hypothesis that it may, but there is a big difference between a hypothesis, however compelling, and actual data to show that is how things are together. One of the hypotheses is that untreated HIV leads to chronic inflammation and the chronic inflammation progresses the end organ diseases, renal, liver disease and etc. That is what the START study aims to do – study whether it is actually possible to prevent the serious non AIDS events by initiation of therapy earlier, we don’t know and that’s why we need to do the study.
So, it’s too early to say how correct the inflammation hypothesis is?
I have seen data recently to suggest it may be correct and data to suggest it is not correct. The data sets I am looking at are too small to make conclusive evidence. And that’s fine, we are used to that in research – having research questions, hypotheses that we are debating. Just because we are debating them and just because it is very intriguing doesn’t mean that it is correct. Think back six or eight years ago when everybody thought that it was good to interrupt therapy once in a while. The SMART study showed it was actually extraordinarily harmful. We need to be a little bit more humble and differentiate between what we think we know and what we actually know. To mix those two together is a big mistake.
Do we have enough data to review current guidelines for when HIV-positive patients should start ART?
Absolutely, that would be a huge mistake. That would be to react on indicia rather than on substance and data. We have done that before and we realised at the time it was a big mistake and so the guidelines became very conservative.
How do you respond to concerns over drug toxicity and possible long-term side effects of AntiRetroviral Therapy?
We know that some of the side effects from exposure to drugs but we certainly don’t know all of them. We have only used these drugs for six to up to 10 years and we need to use them for 20, 30, 40 up to 50 years. So, we don’t know what the long term side effects are. There may still be surprises coming up. I have some sense that there may be new surprises in 2010. We are not done in understanding the full profile of adverse effects from using anti-retroviral therapy and we shouldn’t just put people on treatment because we think it may be good, we have to do it because we know it will be good.
What strategies are we putting in place specifically to prevent non-infectious co-morbidities?
That relates to the EACS guidelines on co-morbidities. There is very little mentioning of anti-retroviral therapy but there is a lot of essentially reminding colleagues of the internal medicine background, what they learned in medical school in terms of what are the preventative measures for cardiovascular diseases and how do we actually do that. Well, we calculate the underlying risk of cardiovascular disease, identify those at high risk, and then we consider using statins or aspirin. This is really where HIV medicine and internal medicine are coming together. It is a huge mistake to believe that anti-retroviral treatment is a strong and important intervention to prevent these co-morbidities. We need to remind ourselves of the important contribution that is used in the general population and to start to use them as well in HIV populations. The point is that they are not currently being used appropriately, and hopefully these guidelines will help us and remind colleagues how to do this. I very strongly believe that HIV physicians have an obligation to make sure that these preventative measures are actually implemented. The analogy is there are two chefs to make a fine dinner and it always goes wrong. There needs to be one chef who deals with this, and either it’s the HIV doctor or it’s the general doctor. But the HIV doctor needs to make sure that some one takes care of this.
So, the medical community still has to report success in the management of such diseases?
Absolutely, we need to come away from the situation where we are focusing on the virus. That’s wrong. We are focusing on a human being that happens to be infected with a virus so of course we need to attend to the virus but we still need to tend to the rest of the body.
Looking at recent data, which one of these non-infectious co-morbidities is putting HIV patients at major risk today?
It is very diverse and depends on which person you are talking about. For the co-infected viral hepatitis contracted clearly liver disease is a major problem. For older people it’s the cancers and the cardiovascular disease. In particular, black people are prone to develop renal disease although we see that also being developed in others. So, it depends on who you are, on your lifestyle, age, genetic background, and how good your doctor is. Cardiovascular disease is not a problem in the 35-year olds but it is a big problem in a 55-year old man.
Finally, we are also experiencing a higher prevalence of depression in HIV patients. 20-40% compared to an average of 7% in the general population. How to tackle such an issue?
I agree in principal that depression is a bigger problem in AIDS patients than in the general population, for many good reasons. Being infected with HIV is a stress factor for many people, it creates a trauma for them that it is difficult to deal with for many and on top of that there is social isolation, the stigmatisation, discrimination. Also to some extent although that is by no means the only explanation, there is also a certain lifestyle that is seen to occur more frequently in people with psychiatric disease which gets some people infected with HIV. So it’s a mixture of those. The bottom line is that we need to remind ourselves as HIV doctors that HIV patients are at risk of depression and we need to have tools at our disposal to diagnose that condition because we can help them.
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