中国河南省 HIV 感染者长期二线抗反转录病毒治疗效果及耐药性研究。
Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China.
机构信息
NHC Key Laboratory of AIDS Immunology (China Medical University), Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, No 155, Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Key Laboratory of AIDS Immunology of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
出版信息
BMC Infect Dis. 2018 Nov 15;18(1):571. doi: 10.1186/s12879-018-3489-7.
BACKGROUND
HIV/AIDS patients who fail to respond to first-line treatment protocols are switched to second-line ART. Identifying factors that influence effective second-line treatment can improve utilization of limited medical resources. We investigated the efficacy of long-term second-line anti-retroviral therapy (ART) after first-line virologic failure as well as the impact of non-nucleotide reverse transcriptase inhibitor (NNRTI), nucleotide reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI) resistance mutations and medication adherence on ineffective viral suppression.
METHODS
A total of 120 patients were evaluated at 6, 12, 18, 24, and 48 months after initiation of second-line ART; a paper questionnaire was administered via a face-to-face interview and venous blood samples were collected. CD4 T cell count, viral load, and drug resistance genotypes were quantified.
RESULTS
CD4 T cell counts increased from 170 cells/μL (IQR 100-272) at baseline to 359 cells/μL (IQR 236-501) after 48 months of second-line treatment. Viral load (log) decreased from 4.58 copies/mL (IQR 3.96-5.17) to 1.00 copies/mL (IQR 1.00-3.15). After switching to second-line ART, nine patients newly acquired the NRTI drug-resistant mutation, M184 V/I. No major PI resistance mutations were detected. Logistical regression analysis indicated that medication adherence < 90% in the previous month was associated with ineffective viral suppression; baseline high/low/moderate level resistance to 3TC/TDF was protective towards effective viral suppression.
CONCLUSIONS
Long-term second line ART was effective in the Henan region of China. Drug resistance mutations to NRTIs were detected in patients receiving second-line ART, suggesting that drug resistance surveillance should be continued to prevent the spread of resistant strains. Patient medication adherence supervision and management should be strengthened to improve the efficacy of antiviral treatment.
背景
对一线治疗方案无反应的 HIV/AIDS 患者会转为二线抗逆转录病毒治疗（ART）。确定影响二线治疗效果的因素可以改善有限医疗资源的利用。我们研究了一线病毒学失败后长期二线抗逆转录病毒治疗（ART）的疗效，以及非核苷类逆转录酶抑制剂（NNRTI）、核苷酸逆转录酶抑制剂（NRTI）和蛋白酶抑制剂（PI）耐药突变以及药物依从性对病毒抑制无效的影响。
方法
共 120 例患者在二线 ART 开始后第 6、12、18、24 和 48 个月时进行评估；通过面对面访谈进行纸质问卷调查，并采集静脉血样。定量检测 CD4 T 细胞计数、病毒载量和耐药基因型。
结果
CD4 T 细胞计数从基线时的 170 个细胞/μL（IQR 100-272）增加到二线治疗 48 个月时的 359 个细胞/μL（IQR 236-501）。病毒载量（log）从 4.58 拷贝/mL（IQR 3.96-5.17）降至 1.00 拷贝/mL（IQR 1.00-3.15）。在转为二线 ART 后，9 例患者新出现了 NRTI 耐药突变 M184V/I。未检测到主要的 PI 耐药突变。逻辑回归分析表明，前一个月的药物依从性<90%与病毒抑制无效相关；基线时对 3TC/TDF 的高/低/中度耐药对有效病毒抑制具有保护作用。
结论
在中国河南地区，长期二线 ART 是有效的。接受二线 ART 的患者检测到对 NRTIs 的耐药突变，提示应继续进行耐药监测，以防止耐药株的传播。应加强对患者用药依从性的监督和管理，以提高抗病毒治疗的疗效。
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