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  ID Week
October 2-6, 2013
San Francisco
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"ART-naïve HIV+ adults, but not controls, had BMD loss at the total hip and trochanter sites over 48 weeks" - ART-Naive Adults More Likely to Lose Trochanter BMD Than HIV-Negatives
  IDWeek, October 2-6, 2013, San Francisco
Mark Mascolini
Compared with matched HIV-negative controls, antiretroviral therapy (ART)-naive people with HIV were more likely to lose bone mineral density (BMD) at the trochanter (top of thigh bone) through 48 weeks of follow-up [1]. Systemic inflammation in HIV-positive people appeared to explain this difference.
Associations between vitamin D, inflammation, and BMD in people with HIV remain incompletely understood. Research does show that HIV-positive people have higher odds of reduced BMD and osteoporosis than HIV-negative people [2], and antiretroviral therapy plays a role in bone loss at least in the first year of treatment [3].
To examine these issues more closely in people with no antiretroviral experience, researchers from Cleveland's Case Western Reserve University conducted a 48-week single-site case-control study of 47 adults with HIV and 41 healthy HIV-negative people matched by age, sex, and race to the HIV group. People with HIV all had a CD4 count above 400 and a stable CD4 slope; none had diabetes or an active infection or inflammatory condition, and none were pregnant or breastfeeding. The HIV-negative group had no known condition requiring prescription drugs. At a baseline visit and week 48, the researchers made DXA scans of the hip and lumbar spine and measured vitamin D (23[OH]D), IL-6, hsCRP, sTNFR-I and II, sVCAM-1, and sICAM-1.
By design, the HIV-positive and negative groups were similar in age (average about 39), gender (about two thirds men), and race (about two thirds African American). Body mass index averaged about 26 kg/m(2) in both groups. The HIV group included a significantly larger proportion of current smokers (72% versus 15%, P < 0.0001) and people with HCV infection (19% versus 2%, P = 0.02), both of which are associated with lower BMD. In people with HIV, current CD4 count averaged 625 and viral load 4638 copies. These people had HIV infection for an average 4 years.
At the baseline visit, HIV-positive and negative people had similar median vitamin D levels (13.2 and 15.1 ng/mL, P = 0.63). (Both averages are well below the normal level of 30 ng/mL.) The HIV group had significantly higher median baseline levels of IL-6 (3 versus 2.2 pg/mL, P = 0.005), sTNFR-II (2434 versus 1965 pg/mL, P = 0.008), sVCAM-1 (782 versus 544 ng/mL, P < 0.0001), and sICAM-1 (300 versus 187 ng/mL, P < 0.0001). Vitamin D and marker levels did not change significantly in either group through 48 weeks.
BMD at the baseline visit did not differ significantly between people with and without HIV at the total hip, femoral neck, trochanter, or spine. Nor did the HIV group and the no-HIV group differ in proportions with osteopenia at baseline (33.3% and 32.5%, P = 0.58). Two people with HIV (4.4%) had osteoporosis at the baseline visit. Through 48 weeks of follow-up, people with HIV lost about 0.6% of BMD at the total hip and 1.4% at the trochanter, but those losses did not represent a significant difference from the minimal gains in the HIV-negative group (P = 0.23 and P = 0.09). HIV-negative people lost more BMD at the femoral neck than HIV-positive people, also a nonsignificant difference (P = 0.87).
But 92.5% of people with HIV lost some BMD at any site, compared with 73.0% of HIV-negative controls, and this difference was statistically significant after adjustment for age, sex, race, body mass index, smoking, and HCV infection (P = 0.01). After adjustment for these variables, a significantly bigger proportion of the HIV group lost BMD at the trochanter (73.0% versus 49.0%, adjusted odds ratio 2.8, 95% confidence interval [CI] 1.1 to 7.2, P = 0.03). When the researchers added levels of vitamin D and inflammation markers to the model comparing trochanter BMD loss, the impact of HIV on BMD loss diminished by more than 10%.
Through 48 weeks of follow-up, 20.5% with HIV versus 5.6% without HIV had progression to osteopenia or osteoporosis, a difference that fell short of statistical significance (P = 0.09). Among people with HIV, two factors were independently associated with progression--white race (P = 0.008) and higher baseline IL-6 (P = 0.04).
The Case Western Reserve team concluded that antiretroviral-naive people with HIV may lose BMD--in this study at the total hip and trochanter--through 48 weeks of follow-up off therapy. Statistical analysis indicated that systemic inflammation appeared to explain greater bone loss at the trochanter in people with versus without HIV. And in people with HIV, the inflammatory marker IL-6 was linked to progression to osteopenia or osteoporosis.
1. Hileman CO, Labbato DE, Storer NJ, McComsey GA. Inflammation, vitamin D and change in bone mineral density (BMD) in antiretroviral therapy (ART)-naive HIV-infected and uninfected adults--a 48-week matched prospective cohort study. IDWeek 2013. October 2-6, 2013. San Francisco. Abstract 674.
2. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS. 2006;20:2165-1274. http://www.natap.org/2006/HIV/120406_09.htm
3. McComsey GA, Kitch D, Daar ES, et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011;203:1791-1801. http://jid.oxfordjournals.org/content/203/12/1791.long
Reported by Jules Levin
Inflammation, Vitamin D and Change in Bone Mineral Density in Antiretroviral-Naïve HIV-infected and Uninfected Adults 48-Week Matched Prospective Cohort Study
Corrilynn O Hileman Danielle E Labbato Norma J Storer Grace A McComsey