Slama Laurence, Reddy Susheel, Phair John, Palella Frank J, Brown Todd T
Hôpital Hôtel-Dieu, APHP, Service de Thérapeutique en Immuno-Infectiologie, 1 Place du Parvis Notre-Dame, 75181 Paris cedex 04, France.
Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
J Antimicrob Chemother. 2017 May 1;72(5):1456-1461. doi: 10.1093/jac/dkx011.
Osteoporosis is common among HIV-infected persons and contributes to risk of fragility fracture. While ART initiation is associated with decreases in bone mineral density and increases in bone turnover, the impact of HIV on bone metabolism is unclear.
We identified men at the Chicago site of the Multicenter AIDS Cohort Study who HIV seroconverted while under observation. Concentrations of 25-OH vitamin D, bone turnover markers [procollagen type 1 N terminal propeptide (P1NP), osteocalcin (OC), C-telopeptide (CTX)] and sclerostin were measured from stored serum obtained at pre-HIV infection, pre-ART and post-ART initiation timepoints. Mixed models, with each biomarker as an outcome, were fitted. Timepoint, age, CD4 count (cells/mm 3 ), HIV-viral suppression, season and an age by timepoint interaction term were considered as fixed effects.
Data from 52 participants revealed that median duration between HIV seroconversion and ART initiation was 8.7 years (IQR 3.7-11.6). Median CD4 and plasma HIV-RNA concentrations were 445 (IQR 298.5-689) and 20 184 copies/mL (IQR 6237-64 340), respectively, at the pre-ART timepoint. Multivariate analyses demonstrated pre-HIV infection levels of OC that were higher than pre-ART levels (6.8 versus 5.7 ng/mL, P = 0.04); and pre-ART levels of sclerostin that were higher than post-ART levels (0.033 versus 0.02 ng/mL, P <0.001). No changes in P1NP, CTX and 25-OH vitamin D levels were detected.
HIV seroconversion was associated with decreased OC levels while ART initiation was associated with decreases in sclerostin, a negative regulator of bone formation. Our results suggest that both HIV infection and ART have an impact on bone metabolism in white men.
骨质疏松在感染HIV的人群中很常见，会增加脆性骨折的风险。虽然开始抗逆转录病毒治疗（ART）与骨矿物质密度降低和骨转换增加有关，但HIV对骨代谢的影响尚不清楚。
我们在多中心艾滋病队列研究的芝加哥站点中，确定了在观察期间发生HIV血清转化的男性。从HIV感染前、ART前和开始ART后时间点采集的储存血清中，测量25-羟维生素D、骨转换标志物[I型前胶原N端前肽（P1NP）、骨钙素（OC）、C-末端肽（CTX）]和硬化蛋白的浓度。以每个生物标志物为结果，拟合混合模型。将时间点、年龄、CD4细胞计数（细胞/mm³）、HIV病毒抑制、季节以及年龄与时间点的交互项作为固定效应。
52名参与者的数据显示，HIV血清转化与开始ART之间的中位持续时间为8.7年（四分位间距3.7 - 11.6年）。在ART前时间点，CD4和血浆HIV-RNA浓度的中位数分别为445（四分位间距298.5 - 689）和20184拷贝/mL（四分位间距6237 - 64340）。多变量分析表明，HIV感染前OC水平高于ART前水平（6.8对5.7 ng/mL，P = 0.04）；ART前硬化蛋白水平高于开始ART后水平（0.033对0.02 ng/mL，P <0.001）。未检测到P1NP、CTX和25-羟维生素D水平的变化。
HIV血清转化与OC水平降低有关，而开始ART与骨形成的负调节因子硬化蛋白水平降低有关。我们的结果表明，HIV感染和ART均对白人男性的骨代谢有影响。
