关键词: HIV HIV epidemiology HIV resistance HIV subtype

来  源:   DOI:10.1089/AID.2023.0083

Abstract:
More than 62,000 individuals are currently on antiretroviral treatment within the public health system in Argentina. In 2019, more than 50% of people on ART received non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this context, the second nationwide HIV-1 pretreatment drug resistance surveillance study was carried out between April and December 2019 to assess the prevalence of HIV-1 drug resistance in Argentina using the World Health Organization guidelines. This was a nationwide cross-sectional study enrolling consecutive 18-year-old and older individuals starting ARVs at 19 ART-dispensing centers. This allowed us to estimate a point prevalence rate of resistance-associated mutations (RAMs) with a confidence interval (CI) of 5% (for the total population and for those without antiretroviral exposure). Four-hundred forty-seven individuals were included in the study. The prevalence of mutations associated with resistance was detected in 27.7% (95% CI 25.6-34.9%) of the population. For NNRTI, it was 19.6% (95% CI 16.3-24.5%), for integrase strand transfer inhibitor (INSTI) 6.1% (95% CI 6.1-11.9%), for nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) 3% (95% CI 1.9-5.9%), and for protease inhibitors 1.5% (95% CI 0.7-3.6%). Naive individuals had variants of resistance to NRTIs in 16.8% (95% CI 12.8-21.4) and 5.7% (95% CI 2.9-15.9) to INSTI. For experienced individuals, the prevalence of variants associated with resistance was 30.38% (95% CI 20.8-42.2) for NRTIs and 7.7% (95% CI 2.9-15.9) for INSTI. This study shows an increase in the frequency of nonpolymorphic RAMs associated with resistance to NNRTI. This study generates the framework of evidence that supports the use of schemes based on high genetic barrier integrase inhibitors as the first line of treatment and the need for the use of resistance test before prescribing schemes based on NNRTI. We report for the first time the presence of a natural polymorphism associated with the most prevalent recombinant viral form in Argentina and the presence of a mutation linked to first-line integrase inhibitors such as raltegravir.
摘要:
背景:目前,在阿根廷的公共卫生系统中,有超过62,000人正在接受抗逆转录病毒治疗。2019年,超过50%的ART患者接受了NNRTI。
目的:使用WHO指南评估阿根廷HIV-1耐药性的流行情况。
方法:这是一项全国性的横断面研究,在19个ARV分配中心连续招募18岁及以上的个体开始使用ARV。这使我们能够估计aCI为5%的抗性相关突变(RAM)的点患病率(对于总人口和没有抗逆转录病毒暴露的人群)。
结果:本研究纳入了447名个体。在27.7%(95CI25.6-34.9%)的人群中检测到与耐药性相关的突变患病率。对于NNRTI,为19.6%(CI9516.3-24.5%),INSTI6.1%(CI956.1-11.9%),NRTI3%(CI951.9-5.9%)和PI1.5%(CI950.7-3.6%)。幼稚个体对INSTI有16.8%(CI9512.8-21.4)和5.7%(CI952.9-15.9)的NRTI抗性变体。对于有经验的人,与耐药相关的变异体的患病率对于NRTI为30.38%(95CI20.8~42.2),对于INSTI为7.7%(CI952.9~15.9).
结论:在阿根廷进行的具有全国代表性采样的第二项研究表明,与NNTRI抗性相关的非多态抗性相关突变(RAM)的频率增加。这项研究产生了证据框架,支持使用基于高遗传屏障整合酶抑制剂(例如DTG)的方案作为一线治疗,并且需要在基于非核苷抑制剂的处方方案之前使用抗性测试逆转录酶。我们首次报道了与阿根廷最普遍的病毒重组形式相关的天然多态性的存在,这可能对第一代整合酶抑制剂如raltegravir产生影响。
公众号