The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
Department of Health Systems and Populations, Macquarie University, Sydney, NSW, Australia.
HIV Med. 2020 Sep;21(8):492-504. doi: 10.1111/hiv.12882. Epub 2020 Jun 23.
We assessed whether changes at week 12 in markers of bone turnover, inflammation, and immune activation were associated with clinically important (≥ 5%) bone mineral density (BMD) loss from baseline to week 48 at the proximal femur (hip) and lumbar spine in the SECOND-LINE study.
We measured concentrations of procollagen type 1 pro-peptide (P1NP), carboxyl-terminal collagen crosslinks (CTX), high-sensitivity C-reactive protein (hs-CRP), D-dimer, interleukin (IL)-6, tumor necrosis factor (TNF), neopterin, and soluble CD14 and 163 at weeks 0, 12, and 48 in 123 SECOND-LINE dual-energy X-ray absorptiometry (DXA) substudy participants. Linear regression was used to compare changes in biomarkers. Predictors of ≥ 5% BMD loss were examined using multivariable regression.
The mean age was 38 years, the mean CD4 T-cell count was 252 cells/µL and the mean viral load was 4.2 log HIV-1 RNA copies/mL; 56% of participants were female and 47% were randomized to receive a nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI]-based regimen [91% (53/58) were randomized to receive a tenofovir disoproxil fumarate (TDF)-containing regimen]. Over 48 weeks, 71% in the N(t)RTI arm experienced ≥ 5% hip BMD loss vs. 29% in the raltegravir arm (P = 0.001). Week 12 changes in P1NP and CTX were significantly greater among patients experiencing ≥ 5% hip BMD loss, patients randomized to N(t)RTI, and male patients. Predictors of ≥ 5% hip BMD loss at week 48 were P1NP increase [odds ratio (OR) 5.0; 95% confidence interval (CI) 1.1-27; P < 0.043]; N(t)RTI randomization (OR 6.7; 95% CI 2.0-27.1; P < 0.003), being African, higher baseline CD4 T cell count , and smoking.
In a diverse cohort of viraemic HIV-infected patients, switching to second-line antiretroviral therapy (ART) was associated with clinically significant BMD loss, which was correlated with an early increase in P1NP. Measurement of P1NP may facilitate timely interventions to reduce rapid BMD loss among at-risk patients.
我们评估了在 SECOND-LINE 研究中，第 12 周时骨转换标志物、炎症标志物和免疫激活标志物的变化是否与第 0 周至第 48 周时近侧股骨（髋部）和腰椎的基线骨密度（BMD）丢失≥5%有关。
我们在 SECOND-LINE 双能 X 射线吸收法（DXA）子研究的 123 名参与者中，分别在第 0、12 和 48 周时测量了前胶原 1 型前肽（P1NP）、羧基末端胶原交联（CTX）、高敏 C 反应蛋白（hs-CRP）、D-二聚体、白细胞介素（IL）-6、肿瘤坏死因子（TNF）、新蝶呤和可溶性 CD14 和 163 的浓度。线性回归用于比较生物标志物的变化。使用多变量回归来检查 BMD 丢失≥5%的预测因素。
参与者的平均年龄为 38 岁，平均 CD4 T 细胞计数为 252 个/µL，平均病毒载量为 4.2 log HIV-1 RNA 拷贝/mL；56%的参与者为女性，47%随机接受核苷（酸）逆转录酶抑制剂[N(t)RTI]为基础的方案[91%（53/58）随机接受含有替诺福韦二吡呋酯（TDF）的方案]。在 48 周内，N(t)RTI 组中 71%的患者出现髋部 BMD 丢失≥5%，而拉替拉韦组中为 29%（P=0.001）。髋部 BMD 丢失≥5%的患者、随机接受 N(t)RTI 的患者和男性患者的第 12 周时 P1NP 和 CTX 的变化明显更大。第 48 周时髋部 BMD 丢失≥5%的预测因素为 P1NP 升高[比值比（OR）5.0；95%置信区间（CI）1.1-27；P<0.043]；N(t)RTI 随机化（OR 6.7；95%CI 2.0-27.1；P<0.003）、非洲裔、较高的基线 CD4 T 细胞计数和吸烟。
在一组多样化的病毒血症 HIV 感染患者中，转换为二线抗逆转录病毒治疗（ART）与临床显著的 BMD 丢失相关，这与 P1NP 的早期增加有关。P1NP 的测量可能有助于及时干预，减少高危患者的快速 BMD 丢失。
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