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Abstract：
BACKGROUND: Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function.
METHODS: The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point.
RESULTS: Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8-8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV1 z-score was - 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load.
CONCLUSIONS: There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function.
BACKGROUND: ClinicalTrials.gov NCT02426112. First registered on 24/04/2015.
METHODS: The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point.
RESULTS: Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8-8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV1 z-score was - 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load.
CONCLUSIONS: There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function.
BACKGROUND: ClinicalTrials.gov NCT02426112. First registered on 24/04/2015.
摘要：
背景：慢性肺病（CLD）在HIV（CWH）儿童中很常见，包括在接受抗逆转录病毒治疗（ART）的儿童中。阿奇霉素具有抗菌和抗炎作用，在多种肺部疾病中可有效改善肺功能。我们调查了CWH与CLD在ART中的肺功能轨迹，纳入了一项阿奇霉素佐剂的随机对照试验。我们还研究了改变阿奇霉素对肺功能影响的因素。
方法：该研究使用了在马拉维和津巴布韦进行的一项双盲安慰剂对照试验的数据，该试验在6至19岁的CWH中进行了为期48周的阿奇霉素（BREATHES：ClinicalTrials.govNCT02426112），年龄为6至19岁，每秒用力呼气量（FEV1）z评分<-1.0。参与者在停止干预后有24周的进一步随访期。基线测量FEV1、用力肺活量(FVC)和FEV1/FVC,计算24、48和72周和z分数值。在每个随访时间点，使用广义估计方程（GEE）模型来确定阿奇霉素对肺功能z评分的平均影响。
结果：总体而言，347名青少年（51%为男性，中位年龄15岁）被随机分配到阿奇霉素或安慰剂组。ART的中位持续时间为6.2（四分位间距：3.8-8.6）年，基线时56.2％的HIV病毒载量<1000拷贝/ml。在基线,平均FEV1z评分为-2.0(0.7),44.7%(n=155)的FEV1z评分<-2,10.1%的患者有微生物学证据表明阿奇霉素耐药.在两个审判武器中，FEV1和FVCz-得分改善了24周,但此后似乎下降。阿奇霉素和安慰剂组之间的FEV1z评分的调整后的总体平均差异为0.004[-0.08,0.09],表明没有阿奇霉素效应,这对于其他肺功能参数是相似的。没有证据表明阿奇霉素效应和基线年龄之间存在相互作用，肺功能,阿奇霉素耐药性或HIV病毒载量。
结论：在任何时间点均未观察到阿奇霉素对肺功能z评分的影响，提示对肺功能无治疗作用。
背景：ClinicalTrials.govNCT02426112。首次注册于2015年4月24日。
方法：该研究使用了在马拉维和津巴布韦进行的一项双盲安慰剂对照试验的数据，该试验在6至19岁的CWH中进行了为期48周的阿奇霉素（BREATHES：ClinicalTrials.govNCT02426112），年龄为6至19岁，每秒用力呼气量（FEV1）z评分<-1.0。参与者在停止干预后有24周的进一步随访期。基线测量FEV1、用力肺活量(FVC)和FEV1/FVC,计算24、48和72周和z分数值。在每个随访时间点，使用广义估计方程（GEE）模型来确定阿奇霉素对肺功能z评分的平均影响。
结果：总体而言，347名青少年（51%为男性，中位年龄15岁）被随机分配到阿奇霉素或安慰剂组。ART的中位持续时间为6.2（四分位间距：3.8-8.6）年，基线时56.2％的HIV病毒载量<1000拷贝/ml。在基线,平均FEV1z评分为-2.0(0.7),44.7%(n=155)的FEV1z评分<-2,10.1%的患者有微生物学证据表明阿奇霉素耐药.在两个审判武器中，FEV1和FVCz-得分改善了24周,但此后似乎下降。阿奇霉素和安慰剂组之间的FEV1z评分的调整后的总体平均差异为0.004[-0.08,0.09],表明没有阿奇霉素效应,这对于其他肺功能参数是相似的。没有证据表明阿奇霉素效应和基线年龄之间存在相互作用，肺功能,阿奇霉素耐药性或HIV病毒载量。
结论：在任何时间点均未观察到阿奇霉素对肺功能z评分的影响，提示对肺功能无治疗作用。
背景：ClinicalTrials.govNCT02426112。首次注册于2015年4月24日。
