河南省某县获得性免疫缺陷综合征患者二线抗病毒疗效及耐药变异分析

doi:10.3877/cma.j.issn.1674-1358.2017.04.004

中华实验和临床感染病杂志(电子版) ›› 2017, Vol. 11 ›› Issue (04) : 330 -334. doi: 10.3877/cma.j.issn.1674-1358.2017.04.004

临床论著

河南省某县获得性免疫缺陷综合征患者二线抗病毒疗效及耐药变异分析

尚明全¹, 张旻², 尚红²^,^†(

)

^1. 110001　沈阳市，中国医科大学附属第一医院检验科卫计委艾滋病免疫学重点实验室；024000　赤峰市，内蒙赤峰市医院检验科
^2. 110001　沈阳市，中国医科大学附属第一医院检验科卫计委艾滋病免疫学重点实验室

收稿日期:2016-10-10 出版日期:2017-08-15
通信作者: 尚红
基金资助:
国家科技重大专项资助(No. 2008ZX10102)

Effect and drug resistance variation of second-line antiretroviral therapy among patients with acquired immune deficiency syndrome in a county of Henan Province

Mingquan Shang¹, Min Zhang², Hong Shang²^,^†()

^1. Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, the First Affiliated Hospital of China Medical University, Shenyang 110001, China; Clinical Laboratory, Chifeng Municipal Hospital, Chifeng 024000, China.
^2. Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, the First Affiliated Hospital of China Medical University, Shenyang 110001, China

Received:2016-10-10 Published:2017-08-15
Corresponding author: Hong Shang

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引用本文：

尚明全, 张旻, 尚红. 河南省某县获得性免疫缺陷综合征患者二线抗病毒疗效及耐药变异分析[J]. 中华实验和临床感染病杂志(电子版), 2017, 11(04): 330-334.

Mingquan Shang, Min Zhang, Hong Shang. Effect and drug resistance variation of second-line antiretroviral therapy among patients with acquired immune deficiency syndrome in a county of Henan Province[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2017, 11(04): 330-334.

目的

了解我国河南省尉氏县部分获得性免疫缺陷综合征（AIDS）患者在更换二线抗病毒治疗方案后的疗效及耐药情况，并分析可能影响二线方案疗效的相关因素。

方法

对65例AIDS患者在换药前、二线方案治疗6个月、治疗12个月时分别进行随访调查，并分别行CD4⁺ T细胞、病毒载量及耐药情况检测。

结果

队列中65例AIDS患者，经二线方案治疗12个月后，CD4⁺ T细胞的均值与基线相比显著升高（t =-2.417、P = 0.017），病毒载量均值显著降低（t = 2.343、P = 0.021），病毒载量< 400拷贝/ml患者由换药前的6.2%上升至62.3%（χ² = 42.704、P < 0.001）。换药前患者交叉耐药和多药耐药严重，二线方案治疗12个月后，检出耐药患者比例由换药前78.5%（51/65）下降为11.3%（6/53）；更换二线方案治疗前后均未检测到蛋白酶抑制剂（PI）耐药患者。换药前患者CD4⁺ T < 100个/μl和HIV-1 RNA> 10 000拷贝/ml与治疗后病毒载量未能有效抑制相关（OR = 5.14，95%CI：0.99～26.71；OR = 3.36，95%CI：0.66～17.21）。

结论

二线抗病毒方案疗效显著。更换二线方案前后均未发现PI耐药，但检出大量蛋白酶抑制剂次要变异，应对更换二线抗病毒治疗方案患者进行长期的耐药监测。

关键词: 获得性免疫缺陷综合征, 高效抗逆转录病毒治疗, 耐药, 二线治疗方案

Objective

To investigate the efficacy and drug resistance of patients with acquired immune deficiency syndrome (AIDS) in Weishi County of Henan province after the change of second-line antiviral therapy, and to analyze the factors which affect the efficacy of second-line therapy.

Methods

Total of 65 patients with AIDS were followed up before treatment change, 6 months and 12 months after second-line antiviral therapy. The CD4⁺ T cell counts, viral load and genotypic resistance testing were detected, respectively.

Results

Among the cohort of 65 patients with AIDS, treatment for 12 months after the second-line, the mean CD4⁺ T cell significantly increased compared with the baseline (t =-2.417, P = 0.017), the mean viral load decreased significantly (t = 2.343, P = 0.021), and patients of viral load < 400 copies/ml increased from 6.2% to 62.3% (χ² = 42.704, P < 0.001). Cross resistance and multi-drug resistance were severe in patients with baseline. After 12 months of second-line treatment, the proportion of resistant patients was decreased from 78.5% (51/65) to 11.3% (6/53); protease inhibitor (PI) resistant patients weren’t detected before and after treatment with second-line regimens. Before the change of dressing, patients with CD4⁺ T < 100 cells/μl and HIV-1 RNA > 10 000 copies/ml were significantly related to virologic failure (OR = 5.14, 95%CI = 0.99-26.71; OR = 3.36, 95%CI = 0.66-17.21).

Conclusions

The second-line antiretroviral therapy was effective. PI drug resistance wasn’t found before and after the second-line regimens was replaced. However, a large number of minor protease inhibitors mutations were detected. Long-term resistance surveillance should be carried out in patients with second-line antiretroviral therapy.

Key words: Acquired immune deficiency syndrome, Highly active antiretroviral therapy, Drug resistance, Second-line therapy

图1 标本与Maker位置比较图

表1 65例研究对象换药前的基本临床资料

变量		例数
性别[例（%）]
	男	43（61.2）
	女	22（32.8）
CD4⁺ T细胞计数[例（%）]
	< 200个/μl	32（49.2）
	≥ 200个/μl、< 350个/μl	25（38.5）
	≥ 350个/μl	8（12.3）
CD4⁺ T细胞计数均值（ ± s）		212.00 ± 137.056
病毒载量（拷贝/ml）
	< 400拷贝/ml	4（6.2）
	≥ 400拷贝/ml、< 10 000拷贝/ml	16（34.6）
	≥ 10 000拷贝/ml	45（69.2）
病毒载量均值（log）		4.51 ± 1.076
耐药患者[例（%）]		51（78.5）
	PI	0（0.0）
	NRTI	43（66.2）
	NNRTI	51（78.5）
获得序列		62（95.4）

表1 65例研究对象换药前的基本临床资料

变量		例数
性别[例（%）]
	男	43（61.2）
	女	22（32.8）
CD4⁺ T细胞计数[例（%）]
	< 200个/μl	32（49.2）
	≥ 200个/μl、< 350个/μl	25（38.5）
	≥ 350个/μl	8（12.3）
CD4⁺ T细胞计数均值（ ± s）		212.00 ± 137.056
病毒载量（拷贝/ml）
	< 400拷贝/ml	4（6.2）
	≥ 400拷贝/ml、< 10 000拷贝/ml	16（34.6）
	≥ 10 000拷贝/ml	45（69.2）
病毒载量均值（log）		4.51 ± 1.076
耐药患者[例（%）]		51（78.5）
	PI	0（0.0）
	NRTI	43（66.2）
	NNRTI	51（78.5）
获得序列		62（95.4）

图2 入组65例患者CD4⁺ T细胞计数均值

图3 入组65例患者的病毒载量

表2 二线方案治疗后65例患者CD4⁺ T细胞计数和病毒载量

组别	CD4⁺ T细胞均值（ ± s，个⁄μl）	CD4⁺ T细胞计数[例（%）]		病毒载量均值（ ± s，log）	病毒载量[例（%）]
组别	CD4⁺ T细胞均值（ ± s，个⁄μl）	< 200个/μl	≥ 200个/μl		< 400拷贝/ml	≥ 400拷贝/ml
治疗前	212.00 ± 137.06	32（49.2）	33（50.8）	4.51 ± 1.08	4（6.2）	61（93.8）
6个月	247.89 ± 142.78	18（34.6）	26（50.0）	2.43 ± 1.42	35（67.3）	17（32.7）
12个月	291.65 ± 142.76	14（26.4）	39（73.6）	2.17 ± 1.61	33（62.3）	20（37.7）
^a统计量	t =-1.185	χ² = 0.732		t = 6.780	χ² = 48.617
^aP值	0.239	> 0.050		< 0.001	< 0.001
^b统计量	t =-2.417	χ² = 6.389		t = 2.343	χ² = 42.704
^bP值	0.017	0.011		0.021	< 0.001

表2 二线方案治疗后65例患者CD4⁺ T细胞计数和病毒载量

组别	CD4⁺ T细胞均值（ ± s，个⁄μl）	CD4⁺ T细胞计数[例（%）]		病毒载量均值（ ± s，log）	病毒载量[例（%）]
组别	CD4⁺ T细胞均值（ ± s，个⁄μl）	< 200个/μl	≥ 200个/μl		< 400拷贝/ml	≥ 400拷贝/ml
治疗前	212.00 ± 137.06	32（49.2）	33（50.8）	4.51 ± 1.08	4（6.2）	61（93.8）
6个月	247.89 ± 142.78	18（34.6）	26（50.0）	2.43 ± 1.42	35（67.3）	17（32.7）
12个月	291.65 ± 142.76	14（26.4）	39（73.6）	2.17 ± 1.61	33（62.3）	20（37.7）
^a统计量	t =-1.185	χ² = 0.732		t = 6.780	χ² = 48.617
^aP值	0.239	> 0.050		< 0.001	< 0.001
^b统计量	t =-2.417	χ² = 6.389		t = 2.343	χ² = 42.704
^bP值	0.017	0.011		0.021	< 0.001

表3 Logistic回归分析53例患者经二线方案治疗12个月后未到达病毒学抑制相关因素

相关因素		OR（95%CI）
性别（女）		1.19（0.34～4.18）
年龄（> 45岁）		2.11（0.64～6.95）
HAART > 3年		0.12（0.01～1.49）
CD4⁺ T < 100个/μl		5.14（0.99～26.71）
CD4⁺ T ≥ 100、CD4⁺ T < 200个/μl		1.72（0.35～8.48）
CD4⁺ T ≥ 200个/ul		1.0
二线方案起始VL > 10 000拷贝/ml		3.36（0.66～17.21）
二线方案更换NRTI药物数量
	1个NRTI	1.31（0.13～13.74）
	2个NRTI	0.76（0.07～7.98）

表3 Logistic回归分析53例患者经二线方案治疗12个月后未到达病毒学抑制相关因素

相关因素		OR（95%CI）
性别（女）		1.19（0.34～4.18）
年龄（> 45岁）		2.11（0.64～6.95）
HAART > 3年		0.12（0.01～1.49）
CD4⁺ T < 100个/μl		5.14（0.99～26.71）
CD4⁺ T ≥ 100、CD4⁺ T < 200个/μl		1.72（0.35～8.48）
CD4⁺ T ≥ 200个/ul		1.0
二线方案起始VL > 10 000拷贝/ml		3.36（0.66～17.21）
二线方案更换NRTI药物数量
	1个NRTI	1.31（0.13～13.74）
	2个NRTI	0.76（0.07～7.98）

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