Continuous HAART Associated With Decreased Bone Mineral Density, SMART Substudy Finds
An Interview With Birgit Grund, Ph.D.
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 her explanation of the study she presented at ICAAC/IDSA 2008.
My name is Birgit Grund. I am from the University of Minnesota's Coordinating Centers for Biometric Research. I'm a statistician on the SMART study,1 specifically the body composition substudy of SMART.2 In this substudy, X-ray scans were used to measure different measures of body composition, including bone marrow density. We had longitudinal measurements of spine bone marrow density by quantitative computed tomography [QCT], which measures the inside of the bone (the trabecular bone); spine bone marrow density by DEXA [dual-energy X-ray absorptiometry], which measures mostly cortical bone, but also trabecular bone; and bone marrow density by DEXA at the hip. So we have three major bone marrow density locations.
Birgit Grund, Ph.D.
In the SMART trial, patients with CD4+ cell counts greater than 350 were randomized to continuous antiretroviral therapy versus CD4-guided intermittent antiretroviral therapy. [Editor's note: Of the patients who were randomized to receive continuous antiretroviral therapy, 68% had already been on therapy at baseline. Of the patients who were randomized to receive intermittent therapy -- to stop treatment at 350 and resume if their CD4+ cell count fell below 250 -- 78% had been on therapy at baseline. In both arms of the study, the average duration of antiretroviral therapy use at baseline was six years.]
What we saw in the randomized comparison is that at all three measures -- two in the spine, one in the hip -- patients on the continuous antiretroviral therapy arm had lower bone marrow density through follow up than patients on the intermittent antiretroviral therapy arm. The differences were significant.
Could you talk a little bit about the differences?
Differences at the hip between the two study arms were 1.4% off baseline [P = .002]. Differences at the spine, spine QCT, were 2.9% [P = .01]. Differences by DEXA in the spine were 1.2% [P = .05]. Average follow-up was about two years. Of that, time spent off antiretroviral therapy was a little bit over a year in the intermittent therapy arm.
We tried to tease out which drugs contributed most to the decline in bone marrow density, but we had a small cohort of 98 participants. We looked at cumulative use of drugs on antiretroviral therapy. The results were not consistent across the three measurements. What we saw consistently across the three locations is that with continuous antiretroviral therapy, bone density declined more than with intermittent therapy.
Is there any take-home for clinicians back home?
I think further research needs to be done. It's too early to speak about recommendations, but it certainly prompts us to think about guidelines for HIV-infected patients.
Was there anything in the patient characteristics that would be connected to this decrease in bone density?
Twenty-three percent were women. The average age of participants was 44 years. About a quarter of participants were black. A little less than half were white.
Could it be a function of age at all?
Well, it is known that bone marrow density decreases with age, but the decrease is not as high as we have seen it here in this study. It's a little bit higher than what you would expect in the HIV-uninfected population of that age. However, it is known that in cross-sectional studies, persons with HIV tend to have somewhat lower bone marrow density than persons who are not HIV infected.
Thank you very much.
This transcript has been lightly edited for clarity.
- El-Sadr W, and the SMART Study Group. Re-initiation of ART in the CD4-guided ART interruption group in the SMART study lowers risk of opportunistic disease or death. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 36.
- Grund B, Carr A, and the Insight SMART Study Group. Continuous antiretroviral therapy (ART) decreases bone mineral density: results from the SMART study. In: Program and abstracts of the 48th Annual ICAAC/IDSA 46th Annual Meeting; October 25-28, 2008; Washington, D.C. Abstract H-2312a.