Shiau Stephanie, Yin Michael T, Strehlau Renate, Shen Jing, Abrams Elaine J, Coovadia Ashraf, Kuhn Louise, Arpadi Stephen M
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.
Bone. 2020 Sep;138:115500. doi: 10.1016/j.bone.2020.115500. Epub 2020 Jun 23.
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.
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).
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).
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.
我们之前发现，在转换治疗方案2年后，接受基于利托那韦增强型洛匹那韦（LPV/r）与基于依非韦伦的抗逆转录病毒治疗方案的青春期前感染艾滋病毒儿童（CLWH）的骨量较低，但骨转换情况相似。在此，我们评估在接近转换治疗方案时两组之间的骨转换是否存在差异。
随机分组8周后，有108名继续使用LPV/r的儿童和104名转换为依非韦伦的儿童的样本可供分析。测量了骨转换标志物，包括I型胶原C末端肽（CTx）、I型前胶原N末端前肽（P1NP）和骨钙素。还测量了免疫激活标志物，包括白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、可溶性CD14和高敏C反应蛋白（CRP）。
随机分组8周后，我们未检测到治疗组之间CTx浓度（1.42对1.44 ng/mL，p = 0.85）或P1NP浓度（622对513 ng/mL，p = 0.68）存在差异。在8周时，治疗组的IL-6、TNF-α、可溶性CD14和高敏CRP水平也相似。在8周（88.6对67.3，p = 0.001）和2年（67.6对49.8，p = 0.001）时，LPV/r组的骨钙素（ng/mL）均高于依非韦伦组。
总体而言，在接近治疗方案转换的时间点，我们未能检测到接受不同治疗方案且病毒得到抑制的CLWH中P1NP和CTx在骨转换方面存在差异。我们确实观察到，与转换为依非韦伦的儿童相比，继续使用LPV/r的儿童总骨钙素水平更高。未来的研究应侧重于揭示其机制，并确定未羧化骨钙素的扰动是否可以解释蛋白酶抑制剂所导致的一些骨骼副作用。
