PMID- 32590137
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20220126
IS  - 1873-2763 (Electronic)
IS  - 8756-3282 (Print)
IS  - 1873-2763 (Linking)
VI  - 138
DP  - 2020 Sep
TI  - Bone turnover markers in children living with HIV remaining on ritonavir-boosted 
      lopinavir or switching to efavirenz.
PG  - 115500
LID - S8756-3282(20)30280-5 [pii]
LID - 10.1016/j.bone.2020.115500 [doi]
AB  - 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.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Shiau, Stephanie
AU  - Shiau S
AD  - Department of Biostatistics and Epidemiology, Rutgers School of Public Health, 
      Piscataway, NJ, USA.
FAU - Yin, Michael T
AU  - Yin MT
AD  - Department of Medicine, College of Physicians and Surgeons, Columbia University, 
      New York, NY, USA.
FAU - Strehlau, Renate
AU  - Strehlau R
AD  - 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.
FAU - Shen, Jing
AU  - Shen J
AD  - Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia 
      University, New York, NY, USA.
FAU - Abrams, Elaine J
AU  - Abrams EJ
AD  - 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.
FAU - Coovadia, Ashraf
AU  - Coovadia A
AD  - 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.
FAU - Kuhn, Louise
AU  - Kuhn L
AD  - 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.
FAU - Arpadi, Stephen M
AU  - Arpadi SM
AD  - 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.
LA  - eng
GR  - R01 HD061255/HD/NICHD NIH HHS/United States
GR  - R01 HD073952/HD/NICHD NIH HHS/United States
GR  - R01 HD073977/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200623
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Alkynes)
RN  - 0 (Benzoxazines)
RN  - 0 (Cyclopropanes)
RN  - 2494G1JF75 (Lopinavir)
RN  - JE6H2O27P8 (efavirenz)
RN  - O3J8G9O825 (Ritonavir)
SB  - IM
MH  - Alkynes
MH  - Benzoxazines
MH  - Bone Remodeling
MH  - Child
MH  - Cyclopropanes
MH  - *HIV Infections/drug therapy
MH  - Humans
MH  - Lopinavir/therapeutic use
MH  - *Ritonavir/therapeutic use
PMC - PMC8786259
MID - NIHMS1624041
OTO - NOTNLM
OT  - Bone
OT  - Bone turnover markers
OT  - Osteocalcin
OT  - Protease inhibitors
COIS- Declaration of competing interest Stephanie Shiau, Michael T. Yin, Renate 
      Strehlau, Jing Shen, Elaine J. Abrams, Ashraf Coovadia, Louise Kuhn, and Stephen 
      M. Arpadi declare that they have no conflict of interest.
EDAT- 2020/06/27 06:00
MHDA- 2021/06/22 06:00
PMCR- 2022/01/24
CRDT- 2020/06/27 06:00
PHST- 2020/02/14 00:00 [received]
PHST- 2020/05/15 00:00 [revised]
PHST- 2020/06/14 00:00 [accepted]
PHST- 2020/06/27 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/06/27 06:00 [entrez]
PHST- 2022/01/24 00:00 [pmc-release]
AID - S8756-3282(20)30280-5 [pii]
AID - 10.1016/j.bone.2020.115500 [doi]
PST - ppublish
SO  - Bone. 2020 Sep;138:115500. doi: 10.1016/j.bone.2020.115500. Epub 2020 Jun 23.