Assessing and Acting on Cardiovascular Disease Risk in HIV-Infected Patients

A Podcast Discussion With Marshall Glesby, M.D., Ph.D., and Jens Lundgren, M.D.

Executive Editor

Table of Contents


Over the past few years, the HIV clinical realm has seen an increased focus on the constellation of events that are associated with cardiovascular disease. In many ways, our understanding of cardiovascular risk in HIV-infected patients is still in its infancy. There remains a fair amount of uncertainty not only regarding the HIV- or antiretroviral-specific factors that increase this risk, but also regarding the strategies to employ in an effort to prevent, assess or manage the dangers of cardiovascular disease in people with HIV. But there is a lot we do know, and that knowledge can help guide clinicians as they determine the best way forward.

To discuss these issues, we brought together two of the leading minds on cardiovascular disease and HIV for a frank conversation: Marshall Glesby, M.D., Ph.D., the associate chief of the Division of Infectious Diseases and the director of the Cornell HIV Clinical Trials Unit at Weill Cornell Medical College; and Jens Lundgren, M.D., the chief physician and director of the Copenhagen HIV Programme. Both are at the forefront of research efforts in this area.


Myles Helfand: Let's start with an overview of the problem. Dr. Lundgren, if you could start us off; where are we right now in terms of how prevalent cardiovascular complications are among HIV-infected patients?

Jens Lundgren: This is an area that has been very much focused on during the last 10 to 12 years. As a consequence of that, a substantial amount of data have accumulated, which show that the risk of contracting cardiovascular disease for a person with a given age is slightly higher if this person is HIV infected, as opposed to not HIV infected.

The reasons for why there is such an excess risk are heavily discussed, and I think we will have a chance to discuss the details of that as we progress into this. But the theoretical possibilities are that: HIV-positive populations have an increased prevalence of traditional cardiovascular risk factors that drives an increase. For example, we know that the smoking prevalence in HIV-infected persons is higher than in the background population. That's one explanation.

The second potential explanation is that antiviral drugs are affecting the risk. We'll discuss that. The third sort of principle, or theoretical reason, is that the HIV itself is driving that.

There's a lot of research still to do to further understand this. But I think the safe thing to say here is that whatever problem that we have now in 2010 will be exacerbated in the next 10 years, given the fact that probably the strongest risk factor for cardiovascular disease and HIV is age. Obviously, as antiviral therapies keep people alive, they are aging into an age range where we know -- from the data on HIV patients, but also in the general population, of course -- that the risk of cardiovascular disease will increase. So we need, as HIV physicians, to be aware of this and be at increased vigilance around efforts to prevent cardiovascular disease. Because this will be something that, whatever the level of the problems that we have at the moment, will increase because of the aging of the population.

Myles Helfand: Is there research right now to suggest that we're already in the middle of a rising trend of cardiovascular disease among people with HIV?

Jens Lundgren: It's interesting. There are various studies that have been focusing on this. But it seems, at least in the studies that I'm aware of, that we are at a pretty stable level at the moment. I think that's likely because of the fact that there has been such attention on this in the last 10 years and therefore the various preventive efforts are now having an impact, both in terms of dealing with traditional cardiovascular risk factors, as well as antiviral drugs.

So, at the moment, we are not really at an increasing slope, other than the fact that, as more and more people are getting older, one would expect to see more events. Over and above that, at least from the data I've seen, we don't have an emerging big problem. But obviously, we need to be vigilant, too, to maintain this.

Marshall Glesby: If I could add just one thing to that: Clearly, there has been a lot of focus on coronary heart disease in the last 10 to 12 years, as Jens said. But I think there have been some other interesting trends that have emerged in recent years, as well. Particularly, several studies using echocardiography have been presented or published in recent years that suggest that dilated cardiomyopathy -- left ventricular dysfunction, which we used to see fairly commonly in the pre-combination antiretroviral era -- seems to have largely disappeared. But replacing it seems to be a higher prevalence of diastolic dysfunction. In some studies, up to 50% of people with HIV who undergo echoes will have some evidence of diastolic dysfunction -- often mild, and not clear if it's transient, or whether it will persist. I think the available data, although the controls have not necessarily been optimal in all of these studies, suggest that it is more common in people with HIV than in similarly aged controls from the general population.

I think the other interesting observation has been, in recent years, an increasing recognition of what appears to be a primary pulmonary hypertension in people with HIV. It's still fairly uncommon, but seems to be more common than in the general population, as well.

Jens Lundgren: I agree. That's an important observation. Just to supplement, and give the whole spectrum of this: We are studying strokes, as well, as a manifestation. Obviously, the risk factor profiles for strokes are different for coronary heart disease, hypertension being the lead responsible risk factor. But the number of strokes is now not necessarily trivial, pointing to the [need to be] very careful in your assessment of hypertension in your patients.

Risk Factors

Myles Helfand: Let's get into the risk factors for cardiovascular disease. You mentioned at the very beginning, Dr. Lundgren, that the waters are still a bit muddied in that area, as far as precisely what you can attribute to causing an increased cardiovascular disease risk in people with HIV. And it also sounds like, if we're talking about this disease manifesting itself in any number of different types of complications, that we could be looking at a myriad of different risk factors.

Jens Lundgren: That's how cardiovascular disease develops. I would say that, although there's still debate, I think it is pretty consistent from the data, at least that I've seen. The major risk factors are age and gender -- both well-known and pretty irreversible risk factors. And among the modifiable risk factors: diabetes, hypertension and dyslipidemia. Well-known, traditional cardiovascular risk factors are really driving this.

In young HIV-infected persons, the risk of cardiovascular disease is very low. The problem is in -- and therefore the [solution], certainly in terms of prevention, needs to absolutely focus on -- people in the older age range, particularly if they have any of the traditional cardiovascular risk factors. And I, of course, in that instance forgot to mention smoking.

Marshall Glesby: Absolutely. Smoking is a key risk factor. I think the data are pretty consistent that the prevalence of smoking tends to be greater in HIV-infected clinical settings than in other settings.

Jens Lundgren: It's very, very difficult for people to quit. There have been all sorts of attempts in intervention trials to reduce smoking via the application of medical interventions. At least, that's the data I've seen from Europe. I'm interested to see what your perspective is, Marshall. But at least in the European setting, I think it has been really, really difficult to actively intervene from the medical side.

It seems like -- at least, the perspective I'm getting is that -- we need to make sure that people understand the harmful effects, and continue to put that message across that it's really up to you [the patient] to make a decision on whether you want to quit or not. But it is helpful to do.

Marshall Glesby: Absolutely. It's, I think, a challenge for anyone, whether they have HIV or not, obviously, to quit smoking. And I think as clinicians we need to be better about trying to help our patients quit. I think it's easier to write a prescription for a statin and address a lipid problem than it is to deal with a behavioral thing like smoking.

Myles Helfand: To what extent, then, would you feel that increased cardiovascular risk in people with HIV -- particularly as they age -- is due to aging versus, to use smoking as an example, the fact that a person has just been smoking for a long time, and the risk increases? How does that factor in with known or theorized HIV-related, or antiretroviral-related, heart disease risks?

Jens Lundgren: I can try to respond to that from the data that I'm aware of. Let's assume that you have a person that, over the next 10 years, has a 10% risk of developing coronary heart disease. So, if you studied 10 persons, one of them will develop coronary heart disease. This one: that's because of his age and let's say he has a little bit of diabetes, etc., etc.

Let's now assume that person has been smoking. Then whatever risk that he had would be multiplied by around 150%. So, from a 10% risk, he would increase to a 20 to 25% risk. That's what you get, on top of everything else, if you're smoking. If this person quits smoking, that doesn't necessarily mean that his risk goes back to 10%, because it takes some time for the harm from smoking to vanish. But if he actually does that, data that we have accumulated, as well as data from the background population, would argue that, say, after five to seven years, his risk will go back to 10%. So the heart forgives you for smoking.

But it's important that people start to do this at a fairly young age, in cardiovascular terms -- when they at least turn 40 -- because that's where the underlying risk starts to increase, and that's where you get the most [benefit], in terms of prevention from quitting smoking, before you turn 45 and 50, where the risk really starts to kick up.

Controlling Risk

Myles Helfand: All right. Let's focus on that older population, then, particularly in light of the fact that the larger proportion of people living with HIV are 40 or older, and becoming older as time goes on.

We know, for young people, the main thing is to avoid or ameliorate all of the traditional risk factors that can put a person at risk for cardiovascular disease. If your patient is 40 or older, what do you do as an HIV clinician? What is your approach to the assortment of risk factors? How do you factor in something like, for instance, senescence? We've slowly, but increasingly over the past few years, seen signs that suggest that HIV infection itself is somehow accelerating certain aspects of the aging process.

Marshall Glesby: First of all, I'd like to object to your cutoff of age 40 as older.

Myles Helfand: [Laughs.] In my defense, I was only doing so because Dr. Lundgren had mentioned it a minute earlier. I by no means would say 40 is a cutoff.

Marshall Glesby: OK, there you go. The issue of senescence: It's interesting academically, and I think there is a lot of active investigation, trying to sort out the potential roles of immune activation and premature senescence, in terms of the pathogenesis of various complications that we see in people with HIV, including coronary heart disease.

In terms of what we can practically do in a clinical setting at this point: I think we don't really know. There are studies that are planned, or perhaps ongoing, that are looking at different approaches to reduce inflammation and immune activation, and looking at surrogate measures of atherosclerosis and other potential end organ complications.

One issue that has emerged in recent years since the SMART study is concern about uncontrolled HIV. I think probably most of the people listening to this are aware of the SMART study, which randomized people to continuous versus intermittent antiretroviral therapy, based on their CD4 counts. The intermittent arm had an excess of cardiovascular events. A lot of that has been attributed to inflammation related to uncontrolled HIV viremia or bursts of HIV replication. And there have been some nice biomarker studies, which I think Dr. Lundgren has been involved with, that have looked at markers of coagulation and inflammation and associated them with mortality, for example.

So I think controlling HIV is probably an important thing. And the START study, looking at when the optimal time to initiate antiretroviral therapy may be, will hopefully provide important data in this regard.

Jens Lundgren: The SMART study was an interesting study, also to further understand the development of cardiovascular disease and HIV. But obviously it was an interruption study. You're comparing people on treatment that either continued therapy or interrupted therapy. The study was interrupted fairly soon after it was started, given the fact that there was an overwhelming difference in clinical outcome that favored the continued antiviral therapy arm.

Therefore, we've been struggling when we have been analyzing the SMART study, to have a sufficient endpoint to actually look at each of the components by themselves. In, for example, cardiovascular disease, we really didn't have enough endpoint to have a robust finding on that.

What it clearly shows is that you shouldn't interrupt therapy. But whether actually providing antiviral therapy, per se, is a strategy to reduce cardiovascular disease? As Marshall was saying: that's really the study that needs to show this.

We did another publication that came out in the Journal of AIDS recently, looking at biomarkers in the small group of patients in SMART that were not on therapy when they were enrolled, and where we essentially have a sort of miniature of the SMART study; namely, that if they were randomized to the so-called DC [drug conservation] arm, the interruption arm, essentially they just stayed off therapy. And those who were randomized to the VS [virological suppression] arm, they initiated therapy.

It was interesting. It's around 450 patients, but at least in that subset of patients, over a six-month period thereafter, we couldn't find a difference in these inflammatory markers. Again, this is too small of a cohort to really make a generalized statement from. But that was interesting.

So, at least in my picture, it's a very interesting, it's a very compelling, hypothesis. But we really need to nail this before we can say something that can, at least in my opinion, guide, in a robust way, the clinical management.

Myles Helfand: In the meantime, besides the potential HIV-related factor, we have the seminal D:A:D study -- which, of course, you've been intimately involved with, Dr. Lundgren. It investigated the potential tie between cardiovascular risk and specific antiretrovirals or antiretroviral classes.

Jens Lundgren: That's true. That has been an interesting exercise. You can say that the problem with the D:A:D study is that it's not a randomized trial, and therefore whatever we can observe in that study will be mere associations, which may or may not be causal. That's unfortunately the nature of the beast, because we haven't done the large-scale randomized trials to elucidate this.

Of course, when you look at D:A:D data and other data from observational studies, you need to be very cautious around how you interpret them. But at least the data from D:A:D, which have been supported by numerous other observational studies, have suggested that protease inhibitors, at least some drugs in the protease inhibitor class, are associated with an excess risk of cardiovascular disease. I think that's at least pretty consistent in the literature, that that's a problem.

The other observation that has been generated from the D:A:D study data was this highly unexpected association with abacavir [Ziagen]. Although I should emphasize that this signal -- again, we can't really say it was because of abacavir -- but at least the signal was confined to people at high underlying risk, and therefore really not something that is of relevance in people in which the underlying risk is relatively low. But in people with a high underlying risk, we did see a rather striking high rate of coronary heart disease in those on abacavir, as opposed to those who were not. It appeared to be reversible for those who stopped it, at least. Their risk had dropped down to whatever underlying risk that they had because of other factors.

Recently, there's been the suggestion that perhaps the explanation for this is that the drop leads to platelet hyperreactivity: The platelets become more sticky, which, by itself, doesn't cause coronary heart disease. But if you have extensive plaque formation in your coronary arteries, then if your platelet stickiness increases, your propensity to develop clinical symptoms from that will likely increase. And that is at least a potential mechanism.

But again, I would like to emphasize that this is really only relevant for people who have a high underlying risk, and for whom they already have existing subclinical atherosclerotic processes. There's a lot of debate about this, and a lot of controversy, and a lot of different opinions around it, which I think just signals that the research community is trying to deal with the signal, like any other safety signal, and trying to sort it out.

Myles Helfand: In the case of the protease inhibitors, could you put that risk in a little bit of context?

Jens Lundgren: Compared to the abacavir signal, which appeared to be, at least epidemiologically, a rapid turn-on, rapid turn-off signal, it seems like the protease inhibitor signal is more gradual. So the longer you've been on the drug, the greater the problem becomes. So there is that time factor, which was not true for the abacavir signal.

The other thing, again, is that these are expressed in relative terms. Therefore, if your underlying risk is very low, then, for example, doubling your risk because you're on a protease inhibitor really doesn't change your risk materially.

On the other hand, if your underlying risk is fairly substantial -- for example, if you have multiple traditional risk factors and you're getting older -- then it starts to be more clinically relevant to deal with.

Of course, the two ways to deal with it, if I can just complete that, is that you can either consider using another [antiretroviral] drug, or you can start to be more aggressive in your management of traditional cardiovascular risk factors. At least theoretically, both of those should be effective.

Marshall Glesby: I agree completely with what Jens just said. I think we have to be perhaps a little bit cautious just impugning all protease inhibitors. I know that there have been some analyses from D:A:D looking at specific drugs, and probably as more person-years of observation accrue, there may be better power to look at them. But we do know that there can be differences in the class, in terms of effects on insulin sensitivity and lipids. And that may not be all that's driving these associations if they are causal between myocardial infarction and the use of this class of drugs. I think we have a lot to learn, still, about nuances within the class, and what drugs may be worse than others.

Jens Lundgren: Absolutely. We don't, at least in D:A:D, have enough power, as you said, to really claim whether this is a class effect, or whether it's just some individual drugs that drive it. And really the only way to deal with that is to allow for more person-years to accumulate -- which is now happening, but it will probably take another year before we'll have enough data.

One of the drugs that we have been asked about quite a lot is atazanavir [Reyataz]. But that will take at least another year before we'll have enough data to look into that.

Assessing Risk

Myles Helfand: In the meantime, then, when it comes to the brass tacks for a clinician, what factors should they be taking into account when they try to determine cardiovascular risk in an HIV-positive patient? Is it the same exact risk assessment procedure that any clinician would normally use for any patient? Or should they be factoring in things like previous abacavir experience, or length of HIV infection?

Jens Lundgren: I can start by saying that the prediction of underlying risk is becoming quite an important management tool. So therefore I appreciate the question that you're raising here. At least in D:A:D, our advantage is that we can study the observed risk. So whatever risk prediction that you apply, you can essentially compare that risk prediction to what actually happens to patients.

We just went through that exercise recently and published that. What was interesting was that if you used, for example, the Framingham equation, the traditional equation developed with a population on the East Coast of the United States back in the '60s and '70s, at least for relatively younger people -- so that's people below the age of 50, being HIV infected -- the Framingham equation was over-predicting what was actually observed. That may have a logical explanation, given the fact that it's a very different population from where the Framingham equation was developed.

We actually went through the exercise of developing an HIV-specific risk equation that can be used, and which actually takes into account not only traditional risk factors but, as well, for example, abacavir, which remains an independent predictor of the underlying risk in patients. We put that online, so if people are interested in that, they can at least use that for patient management.

As far as I'm aware, that's the only sort-of-validated risk equation in HIV patients. And by validated, I mean that you develop a risk prediction and then you actually compare that to the observed risk. But I'm not sure. I would be curious to hear what Marshall is using to make risk predictions in his cohorts of patients.

Marshall Glesby: Clinically, when I'm faced with an individual patient -- just getting back to part of the original question, in terms of how to approach them -- I think most expert guidelines suggest that we should be monitoring lipids and glucose probably more aggressively than in someone without HIV of a similar age. So I do tend to check lipids, at least annually, depending on what the values are. And I follow fasting glucose and, in select patients, would consider doing an oral glucose tolerance test. I am concerned about undiagnosed diabetes.

I have used the Framingham risk equation, although there may be some subtle differences, in terms of actual event rates. What you've seen in your cohort, compared to what's predicted, I think, is an approximation that's reasonable. I have not used HIV-specific equations to date, but I look forward to trying those out.

I don't order inflammatory markers, like C-reactive protein. I think the data are fairly limited, in terms of the predictive value of C-reactive protein, and whether it is the same in someone with HIV compared to someone without HIV.

There are, I think, some pretty reasonable data from a number of studies suggesting that [C-reactive protein] levels may remain elevated despite controlling HIV replication. I think Jens alluded to the subanalysis from the SMART study, and there are some data from the ACTG [AIDS Clinical Trials Group] trial, as well, that suggest that levels may end up being persistently elevated in some patients, despite controlling the HIV.

So I'm not sure what the role of further risk stratifying using things like C-reactive protein might be. But I think we need further data on that.

Myles Helfand: Would you extend that to other inflammation markers, like IL-6 or D-dimer?

Marshall Glesby: I don't check those markers clinically. I think it will be interesting to see what happens in some of the ongoing studies, in terms of using those markers. I think there are some interventional studies that are planned that will use some of the data that came from SMART, in terms of cutoffs for some of these values and then potentially intervening to reduce inflammation to see if they affect some markers.

But, in 2010 or 2011, are we there yet, in terms of using these things clinically? I personally don't think so. I'm not sure what Jens and his colleagues do across the Atlantic. I'd be interested to hear.

Jens Lundgren: Well, I can just say that I 100% agree with you that, first, in terms of the risk prediction, I think the Framingham equation is an excellent risk prediction tool, which obviously takes into account lipids and the development of diabetes, etc. -- you know, all the traditional risk factors. And it's an excellent way to stratify a cohort.

I certainly also agree with your point about the measurement of inflammatory and coagulation biomarkers. It's a great research tool at the moment to further understand this, but it's really not ready for clinical routine usage.

I think first and foremost, as Marshall already said, because we don't know actually how to react to this: What is a rational intervention in case you find that these biomarkers are elevated? What do you actually do, if you want to practice evidence-based medicine? It's an area of intense research effort at the moment. We really need to sort this out, so we don't start to measure things in people, and start to react to it by giving more medicine when we are unsure whether it actually provides any benefit to them. So I 100% agree with you on that.

Caring for a New Patient

Myles Helfand: This sounds like a very stressful clinical situation. In the context of, let's say, an HIV clinician, a new patient presents. Let's say it's a 45-year-old man who doesn't smoke, but who has a family history of some cardiovascular disease. You do some testing. You find he's got borderline high cholesterol, borderline high triglycerides. So it's not clear that he's a time bomb, but his CD4 count is low, as frequently happens in clinical settings because patients present late. Let's say his CD4 count is 250.

How do you start, as a clinician, to pull apart the different aspects of potential risk factors for complications, and make the decision about when to start antiretroviral therapy, and what to start with, given the potential cardiovascular risks?

Marshall Glesby: In a patient like that, clearly, treating their HIV should be the priority. If their CD4 count is 250, and that's confirmed, then I think most of us would be more focused on that, as the shorter-term issue, rather than the cardiovascular risk factors that you mentioned. Personally, I would see what evolves with treating their HIV.

If someone does have a number of cardiovascular risk factors, I certainly would keep that in mind in terms of selecting an antiretroviral regimen. But for the most part, I think the regimens that we're thinking about using first-line are relatively lipid friendly, and hopefully not causing major metabolic complications, the way some of the older regimens that we used tended to do.

So I would start out with treating the HIV and then certainly, if the patient persisted, or had a worsening lipid problem, then I would address that as appropriate. But I don't know that I would approach that patient fundamentally differently than someone without HIV. In the back of my mind, I might be thinking that their HIV and perhaps their years of uncontrolled HIV could be predisposing them to atherosclerotic changes. But I have not necessarily had that be the driving force, in terms of my decision making. I would focus on modifiable risk factors and perhaps just keeping in mind that they may be at somewhat higher risk because of their underlying HIV infection.

Myles Helfand: How aggressive would you be about incorporating statins and fibrates into the mix if a person has borderline high cholesterol or triglycerides? Where do you decide to start filtering that stuff in, particularly in light of a couple of potential interaction issues here and there between antiretrovirals and some lipid-fighting meds?

Jens Lundgren: First of all, this patient is in need of effective antiviral therapy to improve his overall health. Cardiovascular disease is not the primary focus here. Also, this person, who supposedly has just entered your clinic, he needs to start being comfortable with his HIV disease, and being comfortable with taking medicine and adherence and all sorts of stuff. That's what you need to focus on initially.

Let's now assume that half a year or a year has gone, and he has been stabilized. He is well-suppressed and no major problems have arisen. Then you need to start to assess his underlying risk. If his underlying risk goes above, say, 15% (a 10-year risk) and he has elevated lipids (total cholesterol or LDL cholesterol), I would then, in that case, consider initiating a statin as my primary focus.

Obviously, if he is diabetic, you need to treat that; if he is hypertensive, you obviously need to treat that, also, earlier. But in terms of lipid management, that would be, at least in my regular practice, the strategy: to control his HIV first, and then see how it goes.

Also, if I can just say: We're talking cardiovascular disease here, right? But many people who initiate [antiretroviral] therapy are also starting drugs that can affect other organ systems -- for example, the kidneys. For example, tenofovir [Viread] can impair renal function. Not in many patients, but it can happen. So there are a lot of issues to deal with.

All these things need to be sorted out before you start to think of what will happen thereafter and whether you need additional medications in the mix. At least, that would be how I would approach it. It's not an emergency. I mean, it's something you need to deal with. But you need to, first of all, get his HIV under control.

Myles Helfand: I'm assuming lifestyle and diet changes would also be pretty high on the priority list before you consider any kind of pharmaceutical intervention, right?

Jens Lundgren: Absolutely. This person needs to deal with a lot of issues, right? He's just been told he has HIV. He's just been told that he needs to be on medication for the rest of his life. Whatever sexual health impact that may have -- there are a lot of issues for that person to deal with.

But gradually, you start to get to know your patient well, and understand his background, and can talk about these other sorts of more subtle issues that he needs to start focusing on. At least, that has been my approach so far.

Marshall Glesby: I agree with that completely. And I think, in terms of drug-drug interactions, there are certainly important drug-drug interactions between some of the statins and protease inhibitors, for example, that we do need to keep in mind. But they are not insurmountable problems. If someone needs a statin, we can pick a statin that will not put the person at higher risk of a clinically important drug-drug interaction.

Jens Lundgren: Or just start with a low dose, and then see how it goes.

Myles Helfand: So in most cases, then, it sounds like you guys would not be basing your decision about what to prescribe, in terms of antiretrovirals, on a person's cardiovascular risk profile. Like, we're not talking about holding back on protease inhibitors. As you mentioned a little earlier, Dr. Glesby, the current preferred first-line antiretrovirals are not really believed to be so much of a problem, when it comes to cardiovascular risk. Some of the older ones, though, might be a little bit different. And there are certainly criteria that come into play that might make those drugs more desirable from the standpoint of treating HIV infection. For instance, there may be complications involving a person's prior drug resistance to a preferred first-line drug, or other confounding factors that might prevent certain antiretrovirals from being used.

Would you make any modifications to what you're prescribing, in terms of antiretrovirals, based on cardiovascular risk? Or is that only after everything else has been exhausted?

Marshall Glesby: In the specific patient that you mentioned, it doesn't sound like that person is going to be in a particularly high-risk category, based on the information that you provided. I would probably try to more formally risk-stratify a patient like that. But given what you said, I don't know that cardiovascular risk issues would be the primary driving force, in terms of selecting a regimen. I mean, there are other issues to factor in, in terms of dosing convenience, as you alluded to -- you know, whether the person has any underlying resistance, etc. So it may be a consideration, but I don't know that it's the most important consideration.

Jens Lundgren: I would agree with that.

Marshall Glesby: I think we do have plenty of options. I mean, there's an integrase inhibitor; protease inhibitors that appear to not have major adverse effects on lipids; and, of course, the non-nucleoside option, if the patient is sensitive to non-nukes.

Myles Helfand: That seems like pretty practical, straightforward information: Take it step by step. Tackle the HIV. If there are any risk factors, then tackle the lifestyle and diet issues first. If the risk appears significant -- high cholesterol, high triglycerides -- if they're above that threshold, then move forward with statins or fibrates. But it sounds like neither of you are suggesting a particularly aggressive take on ameliorating or preventing the development of cardiovascular risk. It's more just, "Let's wait and see. Let's treat the HIV. And then see where things go."

Caring for a Patient at High Risk

Marshall Glesby: Well, I'd just like to throw out the caveat that the example that you were giving did not appear to be somebody at high risk. If you had a patient at intermediate or particularly at high risk, then cardiovascular risk issues would be perhaps more important -- at least in my thinking about how to manage that patient.

Jens Lundgren: Absolutely.

Myles Helfand: So you might consider slicing the abacavir out, if abacavir were something that you were considering, if the person already had a high underlying risk of cardiovascular disease. But not otherwise.

Jens Lundgren: That would be my thinking. Again, the alternative to abacavir, if we are talking about that, is tenofovir. And you want to make sure that his kidneys are all right, as well. So you need to keep balanced views on things.

Myles Helfand: That's a really important point: I realize we're focusing very intently on cardiovascular complications, because that's the focus of this discussion. But this should not be done in a vacuum. As both of you mentioned earlier in this talk, there are a number of other complications that can potentially impact people with HIV, and they all need to be taken into account.

Marshall Glesby: I agree.

Final Thoughts for the Treating HIV Clinician

Myles Helfand: This is the part of it that feels stressful to me, if I were to be in a position to make those decisions. It feels like, particularly over the past several years, we have moved from a situation where treating an HIV-infected patient is mostly about just treating the HIV, to [a situation in which] treating an HIV-infected patient, depending on their CD4 count and viral load, is perhaps as much, if not even more, an issue of treating a lot of potential other comorbities that can come into play, and trying to balance the treatment of those, or the prevention of those, with the need to tackle the HIV infection itself. That's a pretty tall order for a lot of HIV clinicians, I would expect. Especially those who have traditionally been just very focused on infectious diseases.

Jens Lundgren: I agree that there's been a switch in the discussion around these things. But I think the underlying theme here is that HIV is bad for you and therefore if you are in need of treatment, you really need the treatment firsthand. And clearly, we have been discussing these other comorbidities more intensely, and we need to deal with them, and deal with them in a graded way, depending on people's underlying risk.

But it hasn't dramatically changed in the last two years; it's just been the focus of discussion. Which is healthy, because that just shows that we are now entering into a stage of managing HIV where we have become a little bit more sophisticated. So it's not only a CD4 and viral load discussion; it's also these other factors.

But, hey; that's not different from the rest of the population, where you need to deal with these issues, as well. So for me that's just a signal that HIV is becoming a normalized condition, where we need to focus on other issues, as well. And that's true for HIV patients, as well as the general population.

Marshall Glesby: I think those of us who are, let's say, infectious disease specialists do have to hone our general internal medicine skills so that we can manage some of these other issues, whether it's lipids or diabetes, etc., just to deal with the overall health status of our patients, rather than just focusing only on the HIV.

Jens Lundgren: And you know, sometimes HIV physicians have completely forgotten their internal medicine training. But what they learned in medical school is still valid. And if they aren't sure about it -- and I want to stress that -- if they aren't sure about it, and have been focusing on infectious disease and have lost some of the cutting-edge knowledge in other specialties, consult with some of your colleagues that are specialists in this. And make sure that you know how to mend these things in 2010.

There's nothing wrong with just admitting, "Well, I'm very good in antiviral therapy, but I don't have my skill set in cardiovascular disease prevention up-to-date." So talk to your cardiologist colleagues and ask them, "What would you do in this situation?" And they will tell you.

Myles Helfand: That seems like a pretty strong note to end on. Unless either of you have anything you'd like to add, I think we'll wrap it up here. Dr. Glesby, Dr. Lundgren, thank you both so much.

This transcript has been lightly edited for clarity.

Myles Helfand is the editorial director of and