Pinoges Loretxu, Schramm Birgit, Poulet Elisabeth, Balkan Suna, Szumilin Elisabeth, Ferreyra Cecilia, Pujades-Rodríguez Mar
*Clinical Research, Epicentre, Paris, France; †Medical Department, Médecins Sans Frontières, Paris, France; ‡Medical Department, Médecins Sans Frontières, Barcelona, Spain; and §Department of Epidemiology and Public Health, University College London, London, United Kingdom.
J Acquir Immune Defic Syndr. 2015 Apr 15;68(5):527-35. doi: 10.1097/QAI.0000000000000513.
Understanding the factors associated with HIV drug resistance development and subsequent mortality is important to improve clinical patient management.
Analysis of individual electronic health records from 4 HIV programs in Malawi, Kenya, Uganda, and Cambodia, linked to data from 5 cross-sectional virological studies conducted among patients receiving first-line antiretroviral therapy (ART) for ≥6 months. Adjusted logistic and Cox-regression models were used to identify risk factors for drug resistance and subsequent mortality.
A total of 2257 patients (62% women) were included. At ART initiation, median CD4 cell count was 100 cells per microliter (interquartile range, 40-165). A median of 25.1 months after therapy start, 18% of patients had ≥400 and 12.4% ≥1000 HIV RNA copies per milliliter. Of 180 patients with drug resistance data, 83.9% had major resistance(s) to nucleoside or nonnucleoside reverse transcriptase inhibitors, and 74.4% dual resistance. Resistance to nevirapine, lamivudine, and efavirenz was common, and 6% had etravirine cross-resistance. Risk factors for resistance were young age (<35 years), low CD4 cell count (<200 cells/μL), and poor treatment adherence. During 4978 person-years of follow-up after virological testing (median = 31.8 months), 57 deaths occurred [rate = 1.14/100 person-years; 95% confidence interval (CI): 0.88 to 1.48]. Mortality was higher in patients with resistance (hazard ratio = 2.08; 95% CI: 1.07 to 4.07 vs. <400 copies/mL), and older age (hazard ratio = 2.41; 95% CI: 1.24 to 4.71 for ≥43 vs. ≤34 years), and lower in those receiving ART for >30 months.
Our findings underline the importance of optimal treatment adherence and adequate virological response monitoring and emphasize the need for resistance surveillance initiatives even in HIV programs achieving high virological suppression rates.
了解与艾滋病毒耐药性发展及后续死亡率相关的因素对于改善临床患者管理至关重要。
分析来自马拉维、肯尼亚、乌干达和柬埔寨4个艾滋病毒项目的个人电子健康记录，并与在接受一线抗逆转录病毒疗法（ART）≥6个月的患者中进行的5项横断面病毒学研究的数据相联系。使用调整后的逻辑回归和Cox回归模型来确定耐药性和后续死亡率的危险因素。
共纳入2257例患者（62%为女性）。开始接受抗逆转录病毒治疗时，CD4细胞计数中位数为每微升100个细胞（四分位间距为40 - 165）。治疗开始后中位数为25.1个月时，18%的患者每毫升HIV RNA拷贝数≥400，12.4%的患者≥1000。在180例有耐药性数据的患者中，83.9%对核苷类或非核苷类逆转录酶抑制剂有主要耐药，74.4%有双重耐药。对奈韦拉平、拉米夫定和依非韦伦耐药很常见，6%有对依曲韦林的交叉耐药。耐药的危险因素包括年轻（<35岁）、CD4细胞计数低（<200个细胞/μL）和治疗依从性差。在病毒学检测后的4978人年随访期间（中位数 = 31.8个月），发生了57例死亡[发生率 = 1.14/100人年；95%置信区间（CI）：0.88至1.48]。有耐药性的患者死亡率更高（风险比 = 2.08；95%CI：1.07至4.07，与<400拷贝/mL相比），年龄较大的患者死亡率更高（≥43岁与≤34岁相比，风险比 = 2.41；95%CI：1.24至4.71），而接受抗逆转录病毒治疗>30个月的患者死亡率较低。
我们的研究结果强调了最佳治疗依从性和充分的病毒学反应监测的重要性，并强调即使在病毒学抑制率高的艾滋病毒项目中也需要开展耐药性监测举措。
