首页|河南省2018年至2022年抗反转录病毒治疗失败的人类免疫缺陷病毒感染/艾滋病患者基因型耐药的影响因素

河南省2018年至2022年抗反转录病毒治疗失败的人类免疫缺陷病毒感染/艾滋病患者基因型耐药的影响因素

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目的 分析河南省抗反转录病毒治疗(ART)失败的人类免疫缺陷病毒(HIV)感染/艾滋病(AIDS)患者基因型耐药的情况及其影响因素,为调整ART方案、减少耐药提供依据。方法 纳入2018年1月至2022年12月河南省接受ART 24周以上并出现病毒学失败(HIV RNA≥500拷贝/mL)的HIV感染/AIDS患者,收集基线CD4+T淋巴细胞计数、ART方案等临床资料,并于郑州市第六人民医院进行HIV-1基因亚型及其耐药序列突变检测,将序列提交美国斯坦福大学HIV耐药解释系统比对检测结果,确定对核苷类反转录酶抑制剂(NRTI)、非核苷类反转录酶抑制剂(NNRTI)、蛋白酶抑制剂(PI)、整合酶抑制剂(INSTI)的基因型耐药结果。采用多因素logistic回归分析ART失败患者发生耐药的影响因素。结果 982例HIV感染/AIDS患者中899例成功扩增获得序列,检出耐药737例,耐药率为 81。98%(737/899),其中对 NRTI、NNRT1、PI、INSTI 的耐药率分别为 71。97%(647/899)、79。31%(713/899)、5。23%(47/899)和2。72%(20/734)。737例耐药患者中发生2类药物同时耐药者最多,占79。78%(588/737),主要为 NRTI+NNRTI 耐药[79。10%(583/737)];99 例(13。43%)仅发生 1 类药物耐药,48例(6。51%)发生3类药物同时耐药,2例(0。27%)对上述4类药物均耐药。共检测到10种HIV-1基因亚型,其中B亚型最多,占59。73%(537/899),其次为流行重组型(CRF)01_AE亚型[21。91%(197/899)]和 CRF07_BC 亚型[9。45%(85/899)]。基线 CD4+T 淋巴细胞计数、ART 方案和HIV-1基因亚型是耐药发生的独立危险因素,基线CD4+T淋巴细胞计数<100/µL的患者发生耐药的风险是CD4+T淋巴细胞计数≥250/µL的4。55倍[95%可信区间(CI)2。69~7。70];使用2NRTIs+NNRTI方案的患者发生耐药的风险是使用2NRTIs+INSTI方案的4。51倍(95%CI 1。75~11。63);感染B亚型和CRF01_AE亚型的患者发生耐药的风险分别是感染CRF07_BC亚型的2。18倍(95%CI 1。10~4。29)和2。70倍(95%CI1。26~5。78)。结论 河南省ART失败的HIV感染/AIDS患者基因型耐药发生率较高,基线低CD4+T淋巴细胞水平、2NRTIs+NNRTI治疗方案、B亚型和CRF01_AE亚型是患者发生耐药的危险因素。
Influencing factors of genotypic drug resistance in people living with human immunodeficiency virus/acquired immunodeficiency syndrome who failed anti-retroviral therapy in Henan Province from 2018 to 2022
Objective To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA)who failed anti-retroviral therapy(ART)in Henan Province,in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods PLWHA with virological failure(human immunodeficiency virus(HIV)RNA ≥500 copies/mL)after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022.Baseline CD4+T lymphocyte counts,ART regimens and other clinical data were collected.HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People's Hospital of Zhengzhou,and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results.Genotypic drug resistance to nucleotide reverse transcriptase inhibitors(NRTI),non-nucleoside reverse transcriptase inhibitors(NNRTI),protease inhibitors(PI)and integrase inhibitors(INSTI)was determined.Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure.Results Among 982 PLWHA,the sequences of 899 cases were successfully amplified,and drug resistance was detected in 737 cases,with the drug resistance rate of 81.98%(737/899).The rates of resistance to NRTIs,NNRTIs,PIs and INSTIs were 71.97%(647/899),79.31%(713/899),5.23%(47/899)and 2.72%(20/734),respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases(79.78%),mainly NRTI and NNRTI concomitant resistance in 583 cases(79.10%).There were 99 cases(13.43%)who developed resistance to only one class of drugs,and those who developed concurrent resistance to three classes of drugs were 48 cases(6.51%),and two cases(0.27%)were found to be resistant to all four classes of drugs mentioned above.A total of 10 HIV genotypes were detected,among which subtype B accounted for the most(59.73%(537/899)),followed by circulating recombinant form(CRF)01_AE subtype(21.91%(197/899))and CRF07_BC subtype(9.45%(85/899)).The risk factors affecting the development of drug resistance were baseline CD4+T lymphocyte counts,ART regimens and HIV-1 genotypes.The risk of drug resistance in patients with baseline CD4+T lymphocyte counts<100/μL was 4.55 times(95%confidence interval(CI)2.69 to 7.70)higher than patients with CD4+T lymphocyte counts≥250/μL,the risk of drug resistance in patients using 2NRTIs+NNRTI regimen was 4.51 times(95%CI 1.75 to 11.63)higer than those using 2NRTIs+INSTI regimen,and patients infected with B and CRF01_AE subtype was 2.18 times(95%CI 1.10 to 4.29)and 2.70 times(95%CI 1.26 to 5.78)higer than those with CRF07_BC subtype,respectively.Conclusions The incidence of genotypic drug resistance in PLWHA with ART failure in Henan Province is high.Low baseline CD4+T lymphocyte counts,2NRTIs+NNRTI regimens,and genotype B and CRF01_AE are risk factors for drug resistance in PLWHA.

HIV infectionsAcquired immunodeficiency syndromeAntiretroviral therapyGenotypic drug resistanceInfluencing factors

孙燕、陈昭云、霍玉奇、冯梦瑶、刘金瑾、杨萱、赵清霞、张晓华、赵淑娴、张雪、王艳

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郑州市第六人民医院感染科,郑州 450015

郑州市第六人民医院临床医学研究中心,郑州 450015

郑州市第六人民医院转化医学研究中心,郑州 450015

人类免疫缺陷病毒感染 获得性免疫缺陷综合征 抗逆转录病毒治疗 基因型耐药 影响因素

河南省医学科技攻关省部共建项目2023年河南省重点研发与推广专项

SB201903030232102311081

2024

中华传染病杂志
中华医学会

中华传染病杂志

CSTPCD北大核心
影响因子:0.791
ISSN:1000-6680
年,卷(期):2024.42(4)