Pretreatment HIV-drug resistance in Mexico and its impact on the effectiveness of first-line antiretroviral therapy: a nationally representative 2015 WHO survey
Pretreatment HIV-drug resistance in Mexico and its impact on the effectiveness of first-line antiretroviral therapy: a nationally representative 2015 WHO survey
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DOI：
10.1016/s2352-3018(16)30119-9
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发表时间：
2016-12-01
期刊：
影响因子：
16.1
通讯作者：
Reyes-Teran, Gustavo
中科院分区：
文献类型：
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作者：
Avila-Rios, Santiago;Garcia-Morales, Claudia;Reyes-Teran, Gustavo
背景世卫组织制定了一项全球艾滋病毒耐药性监测战略，包括评估治疗前艾滋病毒耐药性。我们的目的是做一个全国性的代表性调查，在墨西哥使用WHO推荐的methods.Methods卫生部抗逆转录病毒治疗（ART）诊所在墨西哥，最大的，包括90%的ART启动卫生部（共66），有资格进行调查。我们采用了概率比例设计方法，在全国范围内对25家诊所进行了抽样调查。邀请即将开始治疗的未接受过抗逆转录病毒治疗的HIV患者参加调查;排除了既往暴露于抗逆转录病毒治疗的个体。我们采用斯坦福大学HIV耐药数据库方法，通过对合格受试者血浆标本中的病毒进行桑格测序和下一代测序，评估治疗前HIV耐药情况。我们获得了入组后中位9.4个月（范围6-12）的随访数据。我们调查了人口统计学变量和治疗前的耐药性与单变量和多变量logistic regression.Findings之间的关系2月3日和2015年7月30日，我们筛选了288例患者在25个诊所，其中264提供了成功测序的病毒，没有证据表明目前暴露于抗逆转录病毒药物。采用桑格方法，在这264名参与者中，41名（15.5%，95%CI 11.4-20.5）对任何抗逆转录病毒药物治疗前耐药，28名（10.6%，7.2-15.0）对非核苷类逆转录酶抑制剂（NNRTI）治疗前耐药。13例（4.9%）参与者对依法韦仑和23例（8.7%）参与者对替诺福韦+恩曲他滨+依法韦仑的治疗前耐药水平至少较低（斯坦福大学罚分>= 15）。采用下一代测序，在264名参与者中，38名（14.4%，95%CI 10.4-19.2）对任何抗逆转录病毒药物具有治疗前耐药，26名（9.8%，6.5-14.1）对NNRTI具有治疗前耐药。在ART启动后中位随访8个月（IQR 6.5-9.4，范围5-11）后，135名NNRTI启动者中有97名（72%）实现了病毒抑制（< 50拷贝/mL），相比之下，25名以蛋白酶为基础的方案启动者中有10名（40%）实现了病毒抑制（p=0.0045）。在将治疗前耐药和初始ART方案作为复合变量进行多变量回归后，治疗前耐药的患者开始NNRTI的病毒抑制率显著降低（比值比0.24，95% CI 0.07-0.74; p= 0.014）。解释在墨西哥，NNRTI预处理耐药性显著降低了基于这些药物的一线ART方案的有效性。应考虑在初始ART随访和决策时进行基线HIV耐药性检测。
Background WHO has developed a global HIV-drug resistance surveillance strategy, including assessment of pretreatment HIV-drug resistance. We aimed to do a nationally representative survey of pretreatment HIV-drug resistance in Mexico using WHO-recommended methods.Methods Among 161 Ministry of Health antiretroviral therapy (ART) clinics in Mexico, the largest, including 90% of ART initiators within the Ministry of Health (66 in total), were eligible for the survey. We used a probability-proportional-to-size design method to sample 25 clinics throughout the country. Consecutive ART-naive patients with HIV about to initiate treatment were invited to participate in the survey; individuals with previous exposure to ART were excluded. We assessed pretreatment HIV-drug resistance by Sanger sequencing and next-generation sequencing of viruses from plasma specimens from eligible participants with Stanford University HIV Drug Resistance Database methods. We obtained follow-up data for a median of 9.4 months (range 6-12) after enrolment. We investigated possible relations between demographic variables and pretreatment drug resistance with univariate and multivariate logistic regression.Findings Between Feb 3 and July 30, 2015, we screened 288 patients in 25 clinics, from whom 264 provided successfully sequenced viruses with no evidence of current exposure to antiretroviral drugs. With the Sanger method, of these 264 participants, 41 (15.5%, 95% CI 11.4-20.5) had pretreatment resistance to any antiretroviral drug and 28 (10.6%, 7.2-15.0) had pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). At least low-level pretreatment resistance (Stanford penalty score >= 15) was noted in 13 (4.9%) of participants to efavirenz and in 23 (8.7%) to the combination tenofovir plus emtricitabine plus efavirenz. With next-generation sequencing, of 264 participants, 38 (14.4%, 95% CI 10.4-19.2) had pretreatment resistance to any antiretroviral drug and 26 (9.8%, 6.5-14.1) had pretreatment resistance to NNRTIs. After median follow-up of 8 months (IQR 6.5-9.4, range 5-11) after ART initiation, 97 (72%) of 135 NNRTI initiators achieved viral suppression (< 50 copies per mL) compared with ten (40%) of 25 individuals who started with protease inhibitor-based regimens (p=0.0045). After multivariate regression considering pretreatment resistance and initial ART regimen as composite variables, people starting NNRTIs with pretreatment drug resistance achieved significantly lower viral suppression (odds ratio 0.24, 95% CI 0.07-0.74; p= 0.014) than patients without NNRTI resistance.Interpretation High levels of pretreatment drug resistance were noted in Mexico, and NNRTI pretreatment drug resistance significantly reduced the effectiveness of first-line ART regimens based on these drugs. Baseline HIV-drug resistance testing for initial ART follow-up and decision making should be considered.