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Bone turnover markers in children living with HIV remaining on ritonavir-boosted lopinavir or switching to efavirenz.
Bone. 2020 Jun 23; 138:115500.BONE

Abstract

INTRODUCTION

We previously found lower bone mass but similar bone turnover in pre-pubertal children living with HIV (CLWH) on a ritonavir-boosted lopinavir (LPV/r)-based vs. efavirenz-based antiretroviral therapy regimen 2 years after switch. Here, we evaluate if bone turnover differed between the groups close to the time of switch.

METHODS

Samples from 108 children remaining on LPV/r and 104 children switched to efavirenz were available for analysis 8 weeks post-randomization. Bone turnover markers, including C-telopeptide of type 1 collagen (CTx), procollagen type-I N-terminal propeptide (P1NP), and osteocalcin were measured. Markers of immune activation were also measured, including IL-6, TNF-alpha, soluble CD14 and high-sensitivity C-reactive protein (CRP).

RESULTS

Eight weeks post-randomization, we did not detect differences in CTx (1.42 vs. 1.44 ng/mL, p = 0.85) or P1NP concentrations (622 vs. 513 ng/mL, p = 0.68) between treatment groups. At 8 weeks, the treatment groups also had similar levels of IL-6, TNF-alpha, soluble CD14 and high-sensitivity CRP. Osteocalcin (ng/mL) was higher in the LPV/r than efavirenz group both at 8 weeks (88.6 vs. 67.3, p = 0.001) and 2 years (67.6 vs. 49.8, p = 0.001).

CONCLUSIONS

Overall, we failed to detect difference in bone turnover by P1NP and CTx in virologically-suppressed CLWH on different regimens at a time point close to the switch. We did observe higher levels of total osteocalcin in children remaining on LPV/r compared to children switched to efavirenz. Future studies should focus on uncovering the mechanism and determining whether perturbation in undercarboxylated osteocalcin could explain some of the bone side effects noted with protease inhibitors.

Authors+Show Affiliations

Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA.Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Pediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA; ICAP at Columbia, Mailman School of Public Health, Columbia University, New York, NY, USA.Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Pediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA; ICAP at Columbia, Mailman School of Public Health, Columbia University, New York, NY, USA. Electronic address: sma2@columbia.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32590137

Citation

Shiau, Stephanie, et al. "Bone Turnover Markers in Children Living With HIV Remaining On Ritonavir-boosted Lopinavir or Switching to Efavirenz." Bone, vol. 138, 2020, p. 115500.
Shiau S, Yin MT, Strehlau R, et al. Bone turnover markers in children living with HIV remaining on ritonavir-boosted lopinavir or switching to efavirenz. Bone. 2020;138:115500.
Shiau, S., Yin, M. T., Strehlau, R., Shen, J., Abrams, E. J., Coovadia, A., Kuhn, L., & Arpadi, S. M. (2020). Bone turnover markers in children living with HIV remaining on ritonavir-boosted lopinavir or switching to efavirenz. Bone, 138, 115500. https://doi.org/10.1016/j.bone.2020.115500
Shiau S, et al. Bone Turnover Markers in Children Living With HIV Remaining On Ritonavir-boosted Lopinavir or Switching to Efavirenz. Bone. 2020 Jun 23;138:115500. PubMed PMID: 32590137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bone turnover markers in children living with HIV remaining on ritonavir-boosted lopinavir or switching to efavirenz. AU - Shiau,Stephanie, AU - Yin,Michael T, AU - Strehlau,Renate, AU - Shen,Jing, AU - Abrams,Elaine J, AU - Coovadia,Ashraf, AU - Kuhn,Louise, AU - Arpadi,Stephen M, Y1 - 2020/06/23/ PY - 2020/02/14/received PY - 2020/05/15/revised PY - 2020/06/14/accepted PY - 2020/6/27/pubmed PY - 2020/6/27/medline PY - 2020/6/27/entrez KW - Bone KW - Bone turnover markers KW - Osteocalcin KW - Protease inhibitors SP - 115500 EP - 115500 JF - Bone JO - Bone VL - 138 N2 - INTRODUCTION: We previously found lower bone mass but similar bone turnover in pre-pubertal children living with HIV (CLWH) on a ritonavir-boosted lopinavir (LPV/r)-based vs. efavirenz-based antiretroviral therapy regimen 2 years after switch. Here, we evaluate if bone turnover differed between the groups close to the time of switch. METHODS: Samples from 108 children remaining on LPV/r and 104 children switched to efavirenz were available for analysis 8 weeks post-randomization. Bone turnover markers, including C-telopeptide of type 1 collagen (CTx), procollagen type-I N-terminal propeptide (P1NP), and osteocalcin were measured. Markers of immune activation were also measured, including IL-6, TNF-alpha, soluble CD14 and high-sensitivity C-reactive protein (CRP). RESULTS: Eight weeks post-randomization, we did not detect differences in CTx (1.42 vs. 1.44 ng/mL, p = 0.85) or P1NP concentrations (622 vs. 513 ng/mL, p = 0.68) between treatment groups. At 8 weeks, the treatment groups also had similar levels of IL-6, TNF-alpha, soluble CD14 and high-sensitivity CRP. Osteocalcin (ng/mL) was higher in the LPV/r than efavirenz group both at 8 weeks (88.6 vs. 67.3, p = 0.001) and 2 years (67.6 vs. 49.8, p = 0.001). CONCLUSIONS: Overall, we failed to detect difference in bone turnover by P1NP and CTx in virologically-suppressed CLWH on different regimens at a time point close to the switch. We did observe higher levels of total osteocalcin in children remaining on LPV/r compared to children switched to efavirenz. Future studies should focus on uncovering the mechanism and determining whether perturbation in undercarboxylated osteocalcin could explain some of the bone side effects noted with protease inhibitors. SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/32590137/Bone_turnover_markers_in_children_living_with_HIV_remaining_on_ritonavir-boosted_lopinavir_or_switching_to_efavirenz L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(20)30280-5 DB - PRIME DP - Unbound Medicine ER -
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