February 26, 2007
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[In] the SUN study, [we aimed] to understand the natural history of HIV in the HAART [highly active antiretroviral therapy] era. It's a large CDC [U.S. Centers for Disease Control and Prevention] cohort, similar to the MACS [Multicenter AIDS Cohort Study, an ongoing prospective study of HIV infection in men who have sex with men (MSM) in major U.S. cities] or the HOPS [HIV Outpatient Study, a large U.S. cohort containing more than 7,800 patients who have been followed since 1993] cohort. We're trying to understand metabolic complications of HIV in people who are on highly active antiretroviral therapy.
This poster is really looking at the initial baseline low bone mineral density rates in our cohort. Our cohort consists of about 680 HIV-infected patients from four cities in the United States, including seven different clinics -- the cities are Denver, St. Louis, Minneapolis, and Providence -- and it's very representative of the HIV epidemic.
In terms of our patient population overall, the mean age is about 41. We have about 135 women and 500 men, about 380 Caucasians and 175 African-Americans. Overall, our cohort: 75% of them are on HAART, about 65% of whom are undetectable. About 10% are naïve to therapy.
The first thing that we found in looking at baseline was, 10% of people had osteoporosis, and 52% of people had osteopenia. Right about 62% of people had low bone mineral density. We compared this to a matched cohort from NHANES [National Health and Nutrition Examination Survey, a program of studies that assess the health and nutritional status of about 5,000 persons each year in the United States]. We matched for age, race, gender and BMI. What we found were significantly lower bone marrow density in the SUN study cohorts. There was only 1% of osteoporosis in the NHANES cohort, versus our 10%, so clearly, a much worse bone mineral density.
When we looked at factors that were related, what we really found were some traditional factors, as well as a couple of HIV factors, although in the multivariate analysis, the key things for low bone mineral density were male gender, low BMI or weight, no resistance training, older age, and unemployment. When we looked at the multivariate analysis for osteoporosis we found low BMI [body mass index, i.e., weight adjusted for height], older age, lower CD4+ count, and then longer duration since HIV diagnosis.
We looked at antiretroviral therapy; in the multivariate analysis, there was no association. There was an association with any use of d4T [stavudine, Zerit)] with low bone mineral density. I think, longitudinally, we'll get a lot more information about the role of antiretroviral therapy, as we follow those people over time; and we hope to have more data on that in the future.
I think the take-home message of our poster is that we need to be really assessing our people more at baseline for bone mineral density. Probably the first thing is really identifying people with risk factors. In HIV, [those at risk for low bone mineral density] may not have the traditional risk factors, in that men seem to be affected more [than women, who are tend to be more at risk]. Clearly people with low BMI or weight should be assessed, as well. We should be more aggressive in getting DEXA [dual energy X-ray absorptiometry] scanning then, as well as making sure people have adequate calcium and vitamin D. Then, for people who are osteoporotic, [we need to] get them on alendronate to prevent fractures.
Why do you think male gender was such an important risk factor here?
I think there are a couple of issues. The number one issue is: In our cohort the men are more likely to be Caucasian, and they have a significantly lower BMI. Overall, the male BMI was about 24.9 versus 30 in the women. Clearly, BMI is playing a critical role for the male gender. There may also be a bias in that women are getting diagnosed [with low bone density] earlier, but it's hard to know that absolutely. Their duration of HIV infection may be longer than we're estimating.
Were rates of low bone mineral density in people over 46 comparable between your study group and the HIV-uninfected population?
No. Definitely, we don't see osteoporosis in [HIV-negative] men, generally, until over 65. [We don't see osteoporosis in] women, until [they're] post-menopausal; (Although at 46, for women, that's kind of on the cusp, there, I suppose, of menopause). Clearly, [osteoporosis is] occurring at a much earlier age in people with HIV and it seems to be related more to HIV disease than to antiretroviral therapy. At least, that's what we're finding so far.
Is this an ongoing study?
Yes. This is a prospective cohort that will be going on for five years, so you can expect to continue to see data from us through at least 2011, 2012.
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