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[十年抗逆转录病毒治疗:接受十年高效三联疗法患者的概况]

[A decade of antiretroviral therapy: a profile of patients with 10 years of highly effective triple therapy].

作者信息

Wilson Gonzalo, Wolff Marcelo

机构信息

Unidad de Infectología, Departamento de Medicina, Hospital Carlos van Buren, Valparaíso, Chile.

出版信息

Rev Chilena Infectol. 2012 Jun;29(3):337-43. doi: 10.4067/S0716-10182012000300015.

Abstract

INTRODUCTION

Highly effective antiretroviral triple therapy (TAR3) has led to a significant increase in survival of patients (pts) infected with human immunodeficiency virus. In 1999 it was started in the Chilean public health system, including Arriarán Foundation (FA) access to TAR, reaching full coverage since 2003. By October 31, 2009 124 pts had reached 10 years of uninterrupted TAR3 in FA.

OBJECTIVE

To describe and analyze the profile of pts, their therapeutic regimen (s) and clinical outcomes during 10 years of TAR3.

METHODS

Retrospective descriptive study. We reviewed the records of pts who had reached 10 years of uninterrupted TAR3 in FA. Demographic data, baseline and virological staging at start of TAR3, comorbidities and complications were recorded. Drug regimens used were analyzed, as well as toxicity, virological and immunological outcomes, frequency and reasons for change in therapy. Complications were classified as opportunistic and not opportunistic during this evolution and the latest known clinical and laboratory data were registered. A database program based on Excel was used.

RESULTS

121/124 pts were available for analysis, 76.8% male, male-female ratio was 3.3:1. Baseline median age: 36 years (20-69); CD4 cells 176/ mm³ (8-1,224) with 65.3% < 200; median viral load (STL): 60,078 copies/ml (1,100- 7,900,000); 36.3% were in clinical AIDS stage. Patients received an average of 3.5 therapies regimens during the decade (range, 1 [14 pts, 11.5%] to 7 [3 pts, 2.4%]), with average duration of 42 months each and a median of 36 months. As initial TAR3 regimen 2 backbone nucleoside analogues (ITRN) was the most frequent, with a protease inhibitor (PI) in 51.2% and non-nucleoside RTIs (NNRTIs) in 38.8%. Adverse reactions were the main reason for change of therapy (24.7%), followed by virological failure (24.2%) and treatment simplification (16.6%). At the latest assessment, all with > 10 years of TAR3 median CD4 was 602 cells/mm³, 11 pts (9%) had CD4 < 200/mm³; 85.2% had undetectable VL (< 80 copies/mL); the remaining 14.8% had a median of 1,800 copies/mL. Only 2 pts (1.7%) were in AIDS clinical stage. Current regimens were 2 NRTI plus 1 NNRTI in 61 pts (50.4%), 2 or more NRTI plus 1 PI in 46 (38%). Seventy two pts (60.3%) had chronic comorbidities at latest follow up. Dyslipidemia, hypertension, diabetes mellitus and renal failure were the most frequent conditions; 17 pts (14%) had clinical lipodystrophy secondary to TAR.

CONCLUSION

Achieving a decade of TAR is already a reality and in the short term will be routine. This is rarely achieved with the initial therapeutic regimen. The major obstacles to prolonged maintenance of a single therapeutic regimen have been adverse effects and virological failure, although current drugs with better efficacy and safety profile may allow longer use for each regimen. Despite the difficulty of treating these pts, they can achieve long-term survival with good virologic control, immune recovery and absence of opportunistic complications associated with HIV infection. Nonetheless, the high frequency of non opportunistic chronic comorbidities and antiretroviral therapy side effects after prolonged or life-long use is becoming a major issue.

摘要

引言

高效抗逆转录病毒三联疗法(TAR3)显著提高了感染人类免疫缺陷病毒患者的生存率。1999年,该疗法在智利公共卫生系统启动,包括阿里亚兰基金会(FA)也可使用TAR,自2003年起实现全面覆盖。截至2009年10月31日,FA有124例患者已接受了10年不间断的TAR3治疗。

目的

描述和分析接受TAR3治疗10年期间患者的特征、治疗方案及临床结局。

方法

回顾性描述性研究。我们查阅了FA中已接受10年不间断TAR3治疗的患者记录。记录人口统计学数据、TAR3开始时的基线和病毒学分期、合并症及并发症。分析所使用的药物方案,以及毒性、病毒学和免疫学结局、治疗改变的频率及原因。在此病程中,并发症分为机会性和非机会性,并记录最新的已知临床和实验室数据。使用基于Excel的数据库程序。

结果

121/124例患者可供分析,男性占76.8%,男女比例为3.3:1。基线年龄中位数:36岁(20 - 69岁);CD4细胞176/mm³(8 - 1224),65.3% < 200;病毒载量中位数(STL):60078拷贝/ml(1100 - 7900000);36.3%处于临床艾滋病期。患者在这十年中平均接受3.5种治疗方案(范围为1种[14例患者,11.5%]至7种[3例患者,2.4%]),每种方案平均持续42个月,中位数为36个月。作为初始TAR3方案,2种骨干核苷类似物(ITRN)最常见,51.2%联合蛋白酶抑制剂(PI),38.8%联合非核苷类逆转录酶抑制剂(NNRTIs)。不良反应是治疗改变的主要原因(24.7%),其次是病毒学失败(24.2%)和治疗简化(16.6%)。在最新评估时,所有接受TAR3超过10年的患者CD4中位数为602细胞/mm³,11例患者(9%)CD4 < 200/mm³;85.2%的患者病毒载量不可检测(< 80拷贝/mL);其余14.8%的患者病毒载量中位数为1800拷贝/mL。仅2例患者(1.7%)处于艾滋病临床期。目前的治疗方案为61例患者(50.4%)采用2种核苷类逆转录酶抑制剂加1种非核苷类逆转录酶抑制剂,46例患者(38%)采用2种或更多核苷类逆转录酶抑制剂加1种蛋白酶抑制剂。在最新随访时,72例患者(60.3%)患有慢性合并症。血脂异常、高血压、糖尿病和肾衰竭是最常见的情况;17例患者(14%)有TAR继发的临床脂肪营养不良。

结论

实现十年的TAR3治疗已成为现实,短期内将成为常规治疗。初始治疗方案很少能达到这一目标。单一治疗方案长期维持的主要障碍是不良反应和病毒学失败,尽管目前疗效和安全性更好的药物可能使每种方案使用时间更长。尽管治疗这些患者存在困难,但他们可以通过良好的病毒学控制、免疫恢复以及无HIV感染相关的机会性并发症实现长期生存。然而,长期或终身使用后非机会性慢性合并症和抗逆转录病毒治疗副作用的高发生率正成为一个主要问题。

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