Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study
Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study
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DOI：
10.1186/1471-2334-12-296
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发表时间：
2012-11-12
影响因子：
3.7
通讯作者：
Di Giambenedetto, Simona
中科院分区：
文献类型：
--
作者：
Prosperi, Mattia C. F.;Fabbiani, Massimiliano;Di Giambenedetto, Simona
背景：药物相关毒性一直是抗逆转录病毒治疗中止的主要原因之一。然而，其决定因素并不完全清楚。本研究的目的是探讨一线抗逆转录病毒治疗终止的预测因素，由于不良事件和他们的演变，在最近几年。方法：患者开始一线抗逆转录病毒治疗的回顾性选择。主要终点是由于不良事件而停止治疗的时间，估计发生率，根据临床/人口统计学/化学基线患者的标志物拟合Kaplan-Meier和多变量考克斯回归模型。在1988年至2010年的1，861人年随访期间，观察到302例因不良事件而停药，对应的发生率（95% CI）为0.16（0.14-0.18）。通过Kaplan-Meier估计，90天、180天、1年、2年和5年时无不良事件的概率（95% CI）为0.88（0.86-0.90）、0.85（0.83-0.87）、0.79（0.76-0.81）、0.70（0.67-0.74）、0.55（0.50-0.61）。最具代表性的不良事件是胃肠道症状（28.5%）、血液学（13.2%）或代谢（脂质和葡萄糖代谢、脂肪营养不良）（11.3%）毒性和超敏反应（9.3%）。与不良事件风险增加相关的因素有：年龄较大、CDC C期、女性、同性恋/双性恋风险组（与异性恋）、HBsAg阳性。在药物中，齐多夫定、司他夫定、扎西他滨、去羟肌苷、全剂量利托那韦、茚地那韦以及依法韦仑（实际上推荐用于一线治疗方案）与毒性风险增加相关。此外，HIV基因型F1感染的患者表现出更高的风险的不良事件的趋势。结论：开始抗逆转录病毒治疗后，从不良事件的概率似乎随着时间的推移而减少。在与毒性增加相关的药物中，目前仅推荐一种用于一线治疗方案，但改进了药物制剂。年龄较大、CDC分期、MSM风险因素和性别也与毒性风险增加相关，在设计一线治疗方案时应予以考虑。
Background: Drug-related toxicity has been one of the main causes of antiretroviral treatment discontinuation. However, its determinants are not fully understood. Aim of this study was to investigate predictors of first-line antiretroviral therapy discontinuation due to adverse events and their evolution in recent years.Methods: Patients starting first-line antiretroviral therapy were retrospectively selected. Primary end-point was the time to discontinuation of therapy due to adverse events, estimating incidence, fitting Kaplan-Meier and multivariable Cox regression models upon clinical/demographic/chemical baseline patients' markers.Results: 1,096 patients were included: 302 discontinuations for adverse events were observed over 1,861 person years of follow-up between 1988 and 2010, corresponding to an incidence (95% CI) of 0.16 (0.14-0.18). By Kaplan-Meier estimation, the probabilities (95% CI) of being free from an adverse event at 90 days, 180 days, one year, two years, and five years were 0.88 (0.86-0.90), 0.85 (0.83-0.87), 0.79 (0.76-0.81), 0.70 (0.67-0.74), 0.55 (0.50-0.61), respectively. The most represented adverse events were gastrointestinal symptoms (28.5%), hematological (13.2%) or metabolic (lipid and glucose metabolism, lipodystrophy) (11.3%) toxicities and hypersensitivity reactions (9.3%). Factors associated with an increased hazard of adverse events were: older age, CDC stage C, female gender, homo/bisexual risk group (vs. heterosexual), HBsAg-positivity. Among drugs, zidovudine, stavudine, zalcitabine, didanosine, full-dose ritonavir, indinavir but also efavirenz (actually recommended for first-line regimens) were associated to an increased hazard of toxicity. Moreover, patients infected by HIV genotype F1 showed a trend for a higher risk of adverse events.Conclusions: After starting antiretroviral therapy, the probability of remaining free from adverse events seems to decrease over time. Among drugs associated with increased toxicity, only one is currently recommended for first-line regimens but with improved drug formulation. Older age, CDC stage, MSM risk factor and gender are also associated with an increased hazard of toxicity and should be considered when designing a first-line regimen.