February 11, 2009
There's nothing like hearing the results of studies directly from those who actually conducted the research. In this interview, you'll meet one of these impressive HIV researchers and read his explanation of a study she presented at CROI 2009.
I'm Julian Falutz. I'm a physician. I've been involved in HIV care over 20 years and I work at the Montréal General Hospital at the HIV clinic, where I'm the Director of the HIV Metabolic Clinic.
The work that we're representing today are results of a cross-sectional analysis of DEXA [dual energy x-ray absortiometry] scans done in a cohort of about 130 clinically stable HIV-positive males.1
What we did was based on some previous results that we have where we're concerned that these patients may be losing bone mass -- preferentially at the hip region at a far greater rate than at age-matched controls. There may be a number of reasons for this. It may be related to their drug history. It may be related to the loss of fat that occurs also preferentially at the hip region as a result of the generalized lipoatrophy that some of the patients have been experiencing.
What we did in this analysis is that we compared the results of T scores at three sites -- the lumbosacral spine, the femoral neck and the total hip. We compared them to T scores from DEXA scans that were available in a historical control group of HIV-negative men who were matched 1:1 with our patients and who had been simply referred for DEXA scans by their physicians on the suspicion that they may have bone loss. We had no control over who these patients were, but we had access to their results.
Then we analyzed the T scores at these three sites in these populations of HIV-positive and HIV-negative controls, stratified by age into those less than 50 years old and to those above 50 years old.
What we showed was that in the younger group, those less than 50 years oldwhere the median age was 43, their T scores were significantly less than in the negative controls. In the older group, those with a median age of 56, there was no difference between the HIV positive and the HIV negative populations.
But interestingly, in the younger HIV-positive, they had a similar T score at either the femoral neck or the total hip to the HIV-negative- men who were on average about 15 years older, so suggesting that their hips are similar in terms of their bone mineral density to a control population at least 15 years older.
So an accelerated kind of aging?
An accelerated bone loss, that's right. We're looking at risk factors for this and there's any number that can be speculated, but it's at least a finding, which should lead to further investigation of what's going on. There are a lot of studies suggesting that HIV-positive men and women lose bone mineral density more rapidly than control populations. But we're -- we looked at regional changes and we're a little bit worried about what's happening at the hip with possibly, an increased risk over time of fractures.
Did you look at prevalence of particularly ART [antiretroviral therapy]? Were there any particular drugs that may have helped accelerate the bone loss?
We started to look at that and I don't really have any reliable results at this time. We did a preliminary analysis that we presented in the fall at the annual lipodystrophy meeting and there's a suggestion that there may be an increased use in patients who had been on d4T [stavudine, Zerit], but also on a couple of other non- thymidine analog drugs. I think it's too preliminary for me to make any definitive statement, but we're now starting to put the data together looking at risk factors.
Were many of these patients on the newer medications? We're doing ongoing DEXA scans, usually about every two years in our patients and these were the first DEXA scans that were done.
They were done in these 130 patients. The first DEXA scans that were done in this group of 130 patients were done anywhere between 2001 and 2007, with the median time of about 2003. Overall this is a group who were using drugs that were more common, you know, five years ago than are common now. This is shown in the fact that more people were on older type of regimens, including d4T, etc. than some of the newer drugs. So this a snapshot of what happened in the past, but we do have followup DEXA scans on about half of these patients and we're going to start to do that analysis to see what happens over time in terms of bone loss at the different regions.
Do you have the average time that these men were on HIV medications?
I do. It's right here by each drug. These were heavily treatment-experienced patients.
Could you tell me a little bit about the fracture rate?
There were too few to really make any reliable statements, but we did an analysis looking at using a published fracture risk score for HIV-negative patients who are over the age of 50.
There's no reliable data on correlating T scores with fracture risk in men under the age of 50 that's ever been published. But in the subgroup of our patients who are over the age of 50, most of them were in the 10-year low risk group for fracture risk.
But interestingly enough, in the control group -- in HIV-negative patients -- most of them who were low risk had low risk at the lumbosacral spine, whereas most of our patients, even though most of them were on a low risk group for 10-year fracture risk, most of that risk was found at the femoral neck rather than at the lumbosacral spine, again, suggesting that HIV-positive patients may possibly be at greater risk for hip fractures than controls.
Do you think patients who are just beginning therapy this year,-- if you gave them a DEXA scan, do you think it would different in the newly infected group of people who had never been on antiretroviral treatment?
We know that one important risk factor for bone mineral density loss is duration of HIV infection, so that has to be factored into it. The issue of whether the different drugs are involved is still controversial. But I think pretty much everybody agrees that duration of HIV infection is an important independent risk factor. People who've been infected for less time overall have more bone mineral density.
It hasn't been easy I imagine to look at the two tracks, meaning, duration of HIV infection and duration of being on antiretrovirals and see which one is weighted more importantly.
Yes. That's a very good point. The problem with most cohorts is that we don't know when an individual patient became infected, so the duration of HIV infection at the time of the DEXA scan is not reliable.
Something like the MAX cohort would be able to give better quantitative data on duration of HIV infection, but in those small studies where duration of infection has been l better documented, they clearly show an independent contribution.
As a result of this, are you recommending to patients that they take calcium supplements?
I think calcium supplements need to be seen in light of what the current evidence is. The only evidence we have is in the general population. And, depending on the degree of bone mineral density loss, and obviously other factors need to be looked at like lack of exercise, cigarette smoking and hypogonadism, which are both in the general population and in HIV-infected patients are recognized risk factors. That needs to be determined. And if they have evidence of osteoporosis, consideration should be given for using antiresorptive agents [agents that would help stop bone loss].
As to whether all patients should be on just calcium and vitamin D, I think that's never really been shown to be of benefit in the general population, certainly in younger males without any recognized risk factors. So I think we have to be a little careful.
You can say, "Well, it's only calcium and vitamin D. Big deal. Just take -- you know, pop a vitamin pill," but , it's still extra pills. There's a cost involved. Some people will have GI [gastrointestinal] intolerance, etc. I think for the time being, until better evidence comes along, I would follow published guidelines for management of osteoporosis.
Thank you very much for taking the time to talk with me.