Low Baseline CD4+ Count Is Associated With Greater Bone Mineral Density Loss After Antiretroviral Therapy Initiation
Low Baseline CD4+ Count Is Associated With Greater Bone Mineral Density Loss After Antiretroviral Therapy Initiation
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DOI：
10.1093/cid/cit538
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发表时间：
2013-11-15
影响因子：
11.8
通讯作者：
Brown, Todd T.
中科院分区：
文献类型：
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作者：
Grant, Philip M.;Kitch, Douglas;Brown, Todd T.
背景抗逆转录病毒治疗（ART）开始后2年内，骨密度（BMD）下降2%-6%。ART前免疫缺陷和早期免疫恢复可能导致这种损失。我们汇总了3项在初治患者中开始ART的研究的数据，其中进行了系列全身双能X线吸收扫描。我们使用线性回归来评估基线CD 4（+）和16周CD 4（+）变化（绝对和相对）对96周总BMD较基线变化的影响。我们进行了多变量线性回归，以评估基线变量年龄、性别、种族/民族、体重指数（BMI）、丙型肝炎状态、母研究、人类免疫缺陷病毒1型（HIV-1）RNA水平与分配至含蛋白酶抑制剂（PI）或替诺福韦方案对96周总BMD变化的相关性。纳入的796例受试者的平均96周总BMD损失为2.0%。在多变量分析中，基线CD 4（+）细胞计数与96周BMD丢失显著相关;基线CD 4（+）= 500个细胞/μ L的个体。治疗16周后，CD 4（+）计数的相对增加（而非绝对增加）与BMD的下降显著相关，但在控制了基线CD 4（+）计数后则无相关性。在多变量分析中，年龄较大、女性、较低的BMI、较高的HIV-1 RNA水平以及PI和替诺福韦分配也与BMD下降更大相关。治疗前低CD 4（+）计数，但不是更大的CD 4（+）计数增加，是一个强大的和独立的风险因素，骨丢失后开始抗逆转录病毒治疗。在较高的CD 4（+）计数时开始ART可能会减少骨质疏松症和脆性骨折的负担。
Background. Bone mineral density (BMD) decreases 2%-6% in the 2 years after antiretroviral therapy (ART) initiation. Pre-ART immune deficiency and early immune recovery may contribute to this loss.Methods. We pooled data from 3 studies of ART initiation in treatment-naive patients in which serial whole-body dual-energy X-ray absorptiometry scans were performed. We used linear regression to evaluate effects of baseline CD4(+) and 16-week CD4(+) change (both absolute and relative) on 96-week total BMD change from baseline. We performed multivariable linear regression to assess associations between baseline variables of age, sex, race/ethnicity, body mass index (BMI), hepatitis C status, parent study, human immunodeficiency virus type 1 (HIV-1) RNA level, and assignment to a protease inhibitor (PI)- or tenofovir-containing regimen on 96-week total BMD change.Results. The included 796 subjects had mean 96-week total BMD loss of 2.0%. In multivariable analysis, baseline CD4(+) cell count was significantly associated with 96-week BMD loss; individuals with baseline CD4(+) = 500 cells/mu L. A greater relative, but not absolute, 16-week increase in CD4(+) count was significantly associated with greater declines in BMD, but not after controlling for baseline CD4(+) count. In multivariable analysis, older age, female sex, lower BMI, higher HIV-1 RNA levels, and PI and tenofovir assignment were also associated with greater BMD decline.Conclusions. Low pretreatment CD4(+) count, but not greater CD4(+) count increase, is a strong and independent risk factor for bone loss after ART initiation. ART initiation at higher CD4(+) counts may reduce the burden of osteoporosis and fragility fractures.