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Abstract：
BACKGROUND: HIV infection and its treatment compromises skeletal development (growth and maturation). Skeletal maturity is assessed as bone age (BA) on hand and wrist radiographs. BA younger than chronological age (CA) indicates delayed development. We conducted a cross-sectional study to determine differences between BA and CA (i.e., skeletal maturity deviation [SMD]), and risk factors associated with SMD in peripubertal children with and without HIV established on antiretroviral therapy (ART) including use of tenofovir disoproxil fumarate (TDF).
METHODS: Children with HIV taking ART for at least two years and a comparison group of HIV-negative children, aged 8-16 years and frequency-matched by age and sex, were recruited from HIV clinics and local schools in the same catchment area, in Harare, Zimbabwe. BA was assessed from non-dominant hand-wrist radiographs using the Tanner Whitehouse 3 method. Negative SMD values correspond to delayed development, i.e., BA younger than CA. Multivariable linear regression models determined factors associated with SMD overall, and in children with HIV.
RESULTS: In total, 534 participants (54% males) were included; by design CA was similar in males and females, whether living with or without HIV. Mean (SD) SMD was more negative in CWH than in HIV-negative children in both males [-1.4(1.4) vs. -0.4(1.1) years] and females [-1.1(1.3) vs. -0.0(1.2) years]. HIV infection and weight-for-age Z-score<-2 were associated with more negative SMD in both males and females after adjusting for socio-economic status, orphanhood, pubertal stage, and calcium intake. Age at ART initiation was associated with SMD in both males and females with those starting ART later more delayed: starting ART aged 4-8 years 1.14 (-1.84, -0.43), or over 8 years 1.47 (-2.30, -0.65) (p-value for trend < 0.001). Similar non-significant trends were seen in males. TDF exposure TDF exposure whether < 4years or ≥ 4 years was not associated with delayed development.
CONCLUSIONS: Perinatally-acquired HIV infection and being underweight were independently associated with delayed skeletal maturation in both males and females. Starting ART later was independently associated with skeletal maturation delay in CWH. Given the known effects of delayed development on later health, it is important to find interventions to ensure healthy weight gain through early years and in CWH to initiate ART as early as possible.
METHODS: Children with HIV taking ART for at least two years and a comparison group of HIV-negative children, aged 8-16 years and frequency-matched by age and sex, were recruited from HIV clinics and local schools in the same catchment area, in Harare, Zimbabwe. BA was assessed from non-dominant hand-wrist radiographs using the Tanner Whitehouse 3 method. Negative SMD values correspond to delayed development, i.e., BA younger than CA. Multivariable linear regression models determined factors associated with SMD overall, and in children with HIV.
RESULTS: In total, 534 participants (54% males) were included; by design CA was similar in males and females, whether living with or without HIV. Mean (SD) SMD was more negative in CWH than in HIV-negative children in both males [-1.4(1.4) vs. -0.4(1.1) years] and females [-1.1(1.3) vs. -0.0(1.2) years]. HIV infection and weight-for-age Z-score<-2 were associated with more negative SMD in both males and females after adjusting for socio-economic status, orphanhood, pubertal stage, and calcium intake. Age at ART initiation was associated with SMD in both males and females with those starting ART later more delayed: starting ART aged 4-8 years 1.14 (-1.84, -0.43), or over 8 years 1.47 (-2.30, -0.65) (p-value for trend < 0.001). Similar non-significant trends were seen in males. TDF exposure TDF exposure whether < 4years or ≥ 4 years was not associated with delayed development.
CONCLUSIONS: Perinatally-acquired HIV infection and being underweight were independently associated with delayed skeletal maturation in both males and females. Starting ART later was independently associated with skeletal maturation delay in CWH. Given the known effects of delayed development on later health, it is important to find interventions to ensure healthy weight gain through early years and in CWH to initiate ART as early as possible.
摘要：
背景：HIV感染及其治疗会损害骨骼发育（生长和成熟）。骨骼成熟度评估为手部和腕部X光片上的骨龄（BA）。比实际年龄（CA）年轻的BA表明发育延迟。我们进行了一项横断面研究，以确定BA和CA之间的差异(即，骨骼成熟度偏差[SMD])，以及在抗逆转录病毒治疗（ART），包括使用富马酸替诺福韦酯（TDF），在有和没有HIV的青春期儿童中与SMD相关的危险因素。
方法：HIV感染儿童服用ART至少两年，对照组为HIV阴性儿童，8-16岁，频率按年龄和性别匹配，是从同一集水区的艾滋病毒诊所和当地学校招募的，在哈拉雷,津巴布韦。使用TannerWhitehouse3方法从非显性手腕X射线照片中评估BA。负的SMD值对应于延迟的发展，即，BA比CA年轻。多变量线性回归模型确定了与SMD总体相关的因素，以及感染艾滋病毒的儿童。
结果：总计，534名参与者(54%为男性)被纳入其中；根据设计，男性和女性的CA相似，无论是否患有艾滋病毒。男性CWH的平均（SD）SMD比HIV阴性儿童的SMD更阴性[-1.4（1.4）vs.-0.4（1.1）年]和女性[-1.1（1.3）vs.-0.0（1.2）年]。在调整社会经济地位后，男性和女性的HIV感染和年龄Z评分<-2的体重与更负的SMD相关。孤儿,青春期阶段，和钙的摄入。开始ART的年龄与男性和女性的SMD相关，开始ART的年龄更晚：开始ART的年龄为4-8岁1.14（-1.84，-0.43），或超过8年1.47（-2.30，-0.65）（趋势的p值<0.001）。在男性中也看到了类似的非显著趋势。TDF暴露TDF暴露<4年或≥4年与延迟发育无关。
结论：围产期获得性HIV感染和体重过轻与男性和女性的骨骼成熟延迟独立相关。后来开始ART与CWH的骨骼成熟延迟独立相关。鉴于发育延迟对以后健康的已知影响，重要的是找到干预措施以确保在早期和CWH中的健康体重增加，以便尽早开始ART。
方法：HIV感染儿童服用ART至少两年，对照组为HIV阴性儿童，8-16岁，频率按年龄和性别匹配，是从同一集水区的艾滋病毒诊所和当地学校招募的，在哈拉雷,津巴布韦。使用TannerWhitehouse3方法从非显性手腕X射线照片中评估BA。负的SMD值对应于延迟的发展，即，BA比CA年轻。多变量线性回归模型确定了与SMD总体相关的因素，以及感染艾滋病毒的儿童。
结果：总计，534名参与者(54%为男性)被纳入其中；根据设计，男性和女性的CA相似，无论是否患有艾滋病毒。男性CWH的平均（SD）SMD比HIV阴性儿童的SMD更阴性[-1.4（1.4）vs.-0.4（1.1）年]和女性[-1.1（1.3）vs.-0.0（1.2）年]。在调整社会经济地位后，男性和女性的HIV感染和年龄Z评分<-2的体重与更负的SMD相关。孤儿,青春期阶段，和钙的摄入。开始ART的年龄与男性和女性的SMD相关，开始ART的年龄更晚：开始ART的年龄为4-8岁1.14（-1.84，-0.43），或超过8年1.47（-2.30，-0.65）（趋势的p值<0.001）。在男性中也看到了类似的非显著趋势。TDF暴露TDF暴露<4年或≥4年与延迟发育无关。
结论：围产期获得性HIV感染和体重过轻与男性和女性的骨骼成熟延迟独立相关。后来开始ART与CWH的骨骼成熟延迟独立相关。鉴于发育延迟对以后健康的已知影响，重要的是找到干预措施以确保在早期和CWH中的健康体重增加，以便尽早开始ART。
