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Plasma Sclerostin in HIV-Infected Adults on Effective Antiretroviral Therapy.

ABSTRACT: Sclerostin is linked to bone physiology and cardiovascular disease through the Wnt/?-catenin signaling pathway. The goal of this study was to determine if sclerostin is related to bone physiology and cardiovascular disease during antiretroviral treatment in HIV-infected persons. This was a cross-sectional analysis from study entry into the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV (SATURN) trial, an ongoing randomized trial comparing rosuvastatin to placebo in HIV-infected adults on antiretroviral therapy. Plasma sclerostin was measured at study entry by ELISA from participants with available samples. Spearman correlation and multivariable linear regression were used to test relationships between sclerostin and bone density or bone turnover and cardiovascular disease. Among 139 HIV-infected participants (median age 46 years, CD4 lymphocyte count 614 cells/?l), the median plasma sclerostin level was 444.1 (IQR 330.3, 570.1) pg/ml. Correlations were detected between sclerostin and age (r=0.26), lumbar spine Z-score (r=0.31), RANKL (r=-0.21), carotid intima-media thickness (CIMT, r=0.19), and sVCAM-1 (r=0.27), p<0.05. No significant correlations were detected between sclerostin and current (r=0.006) or nadir CD4 count (r=0.11). While associations between sclerostin, lumbar spine Z-score, and sVCAM-1 were robust to covariate adjustment (p<0.01), association with CIMT was no longer significant (p=0.08). Our findings provide preliminary support for a relationship between sclerostin and bone mineral density in HIV-infected persons. The Wnt/?-catenin pathway should be investigated as a potential mechanism for loss of bone mineral density in treated HIV infection.

SUBMITTER: Erlandson KM

PROVIDER: S-EPMC4505764 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Plasma Sclerostin in HIV-Infected Adults on Effective Antiretroviral Therapy.

Erlandson Kristine M KM O'Riordan MaryAnn M Hileman Corrilynn O CO Rapaport Eric E Labbato Danielle D Campbell Thomas B TB McComsey Grace A GA

AIDS research and human retroviruses 20150527 7

Sclerostin is linked to bone physiology and cardiovascular disease through the Wnt/β-catenin signaling pathway. The goal of this study was to determine if sclerostin is related to bone physiology and cardiovascular disease during antiretroviral treatment in HIV-infected persons. This was a cross-sectional analysis from study entry into the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV (SATURN) trial, an ongoing randomized trial comparing rosuvastatin to placebo in ...[more]

PMID: 25919636

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Project description:For adults with human immunodeficiency virus (HIV) infection who have CD4+ T-cell counts that are greater than 200 and less than 350 per cubic millimeter and who live in areas with limited resources, the optimal time to initiate antiretroviral therapy remains uncertain.We conducted a randomized, open-label trial of early initiation of antiretroviral therapy, as compared with the standard timing for initiation of therapy, among HIV-infected adults in Haiti who had a confirmed CD4+ T-cell count that was greater than 200 and less than 350 per cubic millimeter at baseline and no history of an acquired immunodeficiency syndrome (AIDS) illness. The primary study end point was survival. The early-treatment group began taking zidovudine, lamivudine, and efavirenz therapy within 2 weeks after enrollment. The standard-treatment group started the same regimen of antiretroviral therapy when their CD4+ T-cell count fell to 200 per cubic millimeter or less or when clinical AIDS developed. Participants in both groups underwent monthly follow-up assessments and received isoniazid and trimethoprim-sulfamethoxazole prophylaxis with nutritional support.Between 2005 and 2008, a total of 816 participants--408 per group--were enrolled and were followed for a median of 21 months. The CD4+ T-cell count at enrollment was approximately 280 per cubic millimeter in both groups. There were 23 deaths in the standard-treatment group, as compared with 6 in the early-treatment group (hazard ratio with standard treatment, 4.0; 95% confidence interval [CI], 1.6 to 9.8; P=0.001). There were 36 incident cases of tuberculosis in the standard-treatment group, as compared with 18 in the early-treatment group (hazard ratio, 2.0; 95% CI, 1.2 to 3.6; P=0.01).Early initiation of antiretroviral therapy decreased the rates of death and incident tuberculosis. Access to antiretroviral therapy should be expanded to include all HIV-infected adults who have CD4+ T-cell counts of less than 350 per cubic millimeter, including those who live in areas with limited resources. (ClinicalTrials.gov number, NCT00120510.)

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Dataset Information

Plasma Sclerostin in HIV-Infected Adults on Effective Antiretroviral Therapy.

Publications

Plasma Sclerostin in HIV-Infected Adults on Effective Antiretroviral Therapy.

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