Pretreatment integrase strand transfer inhibitor resistance in Tianjin, China.
Pretreatment integrase strand transfer inhibitor resistance in Tianjin, China.
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中国天津地区整合酶链转移抑制剂治疗前耐药性研究。
DOI：
10.1097/cm9.0000000000002898
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发表时间：
2023-11-20
影响因子：
6.1
通讯作者：
中科院分区：
文献类型：
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作者：
人类免疫缺陷病毒（HIV）感染是全世界公共卫生的一个重大而紧迫的问题。[1]在1990年代中期，抗逆转录病毒疗法的广泛使用导致艾滋病毒感染管理的重大范式转变，从而将其预后从威胁生命的疾病转变为慢性和可管理的健康状况。根据以前的研究，目前正在接受抗逆转录病毒治疗的艾滋病毒感染者（PLWH）显示，与艾滋病毒感染相关的发病率和死亡率都有所下降，沿着，将病毒传播给他人的风险也有所降低。[2-5]整合酶链转移抑制剂（INSTI）是最新的一类ART药物，表现出强大的效力，耐药屏障高，药物相互作用最小，耐受性极佳。[6，7] 2009年，中国食品药品监督管理总局（CFDA）批准雷特格韦（RAL）作为首个用于治疗HIV/获得性免疫缺陷综合征（AIDS）的药物，随后分别于2015年、2018年、2019年和2023年批准度鲁特韦（DTG）、埃替格韦（EVG）、比替格韦（BIC）和卡博特格韦（CAB）。自2018年以来，INSTI方案已被建议为中国国家艾滋病诊断和治疗指南的首选一线ART。[8]然而，INSTI的使用受到限制，在中国大陆的大部分地区，由于其成本高。因此，在中国，超过80%的PLWH在国家免费抗逆转录病毒治疗项目（NFATP）下接受免费替诺福韦/齐多夫定+拉米夫定+依法韦仑。[8，9]自2020年以来，EVG、DTG和BIC等INSTI的费用逐步下降，目前已纳入中国医疗保险。大城市的地方医疗保险可以支付50-90%的费用，提供大量的报销政策;因此，越来越多的艾滋病毒携带者选择了基于INSTI的治疗方案。截至2022年底，天津近一半的艾滋病毒携带者正在接受INSTI控制方案。INSTI的使用显著增加，导致INSTI相关耐药突变的稳步出现。在中国进行的有限调查表明，在北京和深圳等大城市，抗逆转录病毒初治的PLWH中，耐药水平相对较低。[10然而，天津地区初治患者中的耐药率仍不清楚。本研究评估了中国天津市HIV-1感染的ART初治个体中INSTI相关耐药的患病率。本研究招募了天津市第二人民医院2020年1月1日至2023年4月1日期间的629名ART初治个体。本研究的入选标准如下：（1）天津市第二人民医院门诊患者;（2）HIV-1血清阳性;（3）年龄≥ 18岁;（4）既往未接受过抗病毒治疗;（5）提供知情同意书并可接受耐药检测的受试者。排除标准如下：妊娠、哺乳期妇女、资料不完整和拒绝提供知情同意书。在开始ART之前，从参与者中收集5 mL血液。从NFATP数据库中获得基线临床和人口统计学数据，包括性别、年龄、传播途径、CD 4计数和病毒载量。本研究按照《赫尔辛基宣言》进行，并获得天津市第二人民医院伦理委员会批准（编号：2015-13）。所有参与研究的受试者均提供了书面知情同意书。
Human immunodeficiency virus (HIV) infection is a significant and pressing concern for public health worldwide.[1] Midway through the 1990s, the widespread use of antiretroviral therapy (ART) has resulted in a significant paradigm shift in the management of HIV infection, thereby altering its prognosis from a lifethreatening disease to a chronic and managed health condition. According to previous studies, people who are living with HIV (PLWH) that are on current ART have shown a decrease in both the morbidity and mortality associated with HIV infection, along with a decreased risk of transmitting the virus to others.[2–5] Integrase strand transfer inhibitors (INSTIs) are the most recent category of ART medications, exhibiting strong potency, high barrier to resistance, minimal drug interactions, and excellent tolerability.[6, 7] In 2009, the Chinese Food and Drug Administration (CFDA) authorized raltegravir (RAL) for the first INSTI for the treatment of HIV/acquired immune deficiency syndrome (AIDS), followed by the approval of dolutegravir (DTG), elvitegravir (EVG), bictegravir (BIC), and cabotegravir (CAB) in 2015, 2018, 2019, and 2023, respectively. Since 2018, INSTI-based regimens have been suggested as the preferred first-line ART following the Chinese National Guidelines for HIV/AIDS Diagnosis and Treatment.[8] However, the use of INSTIs is restricted in most regions of the Chinese mainland owing to their high cost. Therefore,> 80% of PLWH in China receive free tenofovir/zidovudine+ lamivudine+ efavirenz under the National Free Antiretroviral Treatment Program (NFATP).[8, 9] Since the year 2020, the cost of INSTIs such as EVG, DTG, and BIC has progressively decreased and is currently covered by Chinese medical insurance. Local health insurance in major cities could cover 50–90% of the cost, providing a substantial reimbursement policy; consequently, an increasing proportion of PLWH selected INSTI-based regimens. By the end of 2022, nearly half of the PLWH in Tianjin were on INSTI-containment regimens. There has been a notable rise in the use of INSTIs, leading to the steady emergence of INSTI-related resistance mutations. Limited investigations in China indicated a relatively low level of INSTI resistance among antiretroviral-naïve PLWH in large cities, such as Beijing and Shenzhen.[10, 11] However, the prevalence of INSTI resistance among treatment-naïve individuals in Tianjin remains unknown. This study evaluated the prevalence of INSTI-associated drug resistance among ART-naïve individuals infected with HIV-1 in Tianjin, China.The current study recruited 629 ART-naïve individuals from Tianjin Second People’s Hospital between January 1, 2020, and April 1, 2023. The criteria for inclusion in the study were as follows:(1) outpatients at Tianjin Second People’s Hospital;(2) HIV-1 seropositive;(3) aged≥ 18 years;(4) no prior antiviral treatment; and (5) participants who provided consent and could undergo drug resistance tests. Exclusion criteria were as listed: pregnancy, breastfeeding women, incomplete data, and refusal to give informed consent. Before initiating ART, 5 mL of blood was collected from the participants. Baseline clinical and demographic data were obtained from the NFATP database, including sex, age, transmission route, CD4 count, and viral load. The study was carried out in accordance with the Declaration of Helsinki and with the approval of the Tianjin Second People’s Hospital’s Ethical Committee (No. 2015-13). All subjects participating in the study provided written informed consent.