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Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy.

ABSTRACT: Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomized to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline and months 4 and 12; BMD at the spine (dual-energy X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared with the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (?CTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p ? 0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and ?CTX at month 4 predicted decrease in hip BMD at month 12, whereas increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months.

SUBMITTER: Hoy J

PROVIDER: S-EPMC3657331 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy.

Hoy Jennifer J Grund Birgit B Roediger Mollie M Ensrud Kristine E KE Brar Indira I Colebunders Robert R Castro Nathalie De ND Johnson Margaret M Sharma Anjali A Carr Andrew A

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20130601 6

Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomized to continuous or intermittent ART, plasma m ...[more]

PMID: 23299909

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Project description:BackgroundThe effect of interruption of antiretroviral therapy (ART) on lipoprotein particle subclasses has not been studied. We examined short-term changes in lipids and lipoprotein particles among 332 HIV-infected individuals randomized to interrupt or continue ART in the "Strategies for Management of Antiretroviral Therapy" trial.MethodsLipids and lipoprotein particles measured by nuclear magnetic resonance spectroscopy were compared between randomized groups at month 1; associations with inflammatory and coagulation markers (high sensitivity C-reactive protein; interleukin 6; amyloid A; amyloid P; D-dimer; prothrombin fragment 1 + 2) were assessed.ResultsCompared with continuation of ART, treatment interruption resulted in substantial declines in total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglyceride, at month 1 but had little net effect on total/HDL cholesterol ratio [baseline-adjusted mean difference [95% confidence interval (CI)] interruption versus continuation arms: -0.10 (-0.59 to 0.38); P = 0.67]. ART interruption resulted in declines in total, large, and medium very low density lipoprotein (VLDL) particle concentrations (VLDL-p) and total and medium HDL-p. However, there was no change in small HDL-p [baseline-adjusted percentage difference between arms: -4.6% (-13.1%, +5.1% ); P = 0.35], small LDL-p [-5.0% (-16.9%, +8.6%); P = 0.45], or other LDL-p subclasses. Changes in lipid parameters on ART interruption did not differ according to baseline ART class (protease inhibitor versus non-nucleoside reverse transcriptase inhibitor) but were negatively associated both with changes in HIV viral load and with changes in inflammatory and coagulation markers, particularly D-dimer.ConclusionsThese results suggest that ART interruption does not favorably influence overall lipid profile: there was little net effect on total/HDL cholesterol ratio, and no change in small LDL-p or small HDL-p, the lipoprotein particle subclasses most consistently linked to coronary risk. Short-term declines in lipid parameters after ART interruption were not associated with class of ART and may be linked to increases in viral replication, inflammation and coagulation.

Dataset Information

Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy.

Publications

Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy.

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