柬埔寨金瓯医院ESTHER项目中初治及接受过抗逆转录病毒治疗的患者的病毒学失败及HIV-1耐药突变情况
Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.
作者信息
Barennes Hubert, Guillet Stéphanie, Limsreng Setha, Him Sovanvatey, Nouhin Janin, Hak Chanroeurn, Srun Chanvatey, Viretto Gerald, Ouk Vara, Delfraissy Jean Francois, Ségéral Olivier
机构信息
Agence Nationale de Recherche sur le VIH et les Hepatites (ANRS), Phnom Penh, Cambodia; ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Univ. Bordeaux, Bordeaux, France; Epidemiology Unit, Pasteur Institute, Phnom Penh, Cambodia.
Agence Nationale de Recherche sur le VIH et les Hepatites (ANRS), Phnom Penh, Cambodia; Assistance Publique - Hôpitaux de Paris (AP-HP), Département de Médecine Interne et Immunologie Clinique, Centre Hospitalier Universitaire de Bicêtre, Le Kremlin-Bicêtre, France.
出版信息
PLoS One. 2014 Aug 28;9(8):e105736. doi: 10.1371/journal.pone.0105736. eCollection 2014.
INTRODUCTION
In resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes.
METHODS
This retrospective study, conducted in 2010-2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia) assessed virological failure (VF) rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL) was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF) (>1,000 copies/ml) underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms.
RESULTS
On a total of 209 patients, 164 (78.4%) were naive and 45 (21.5%) were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30-194) and 279 cells/mm3 (IQR: 103-455) (p<0.001), respectively. Twenty seven patients (12.9%) exhibited VF (95% CI: 8.6-18.2%), including 10 naive (10/164, 6.0%) and 17 pre-treated (17/45, 37.8%) patients (p<0.001). Among these viremic patients, twenty-two (81.4%) were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3%) harbored ≥1 drug resistance mutations (DRMs) whereas 3 (all belonging to pre-treated patients) harbored wild-types viruses. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%). Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations.
CONCLUSION
In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre-treated patients infection should be considered as well.
引言
在资源有限的环境中，进入抗逆转录病毒治疗（ART）项目的患者包括初治患者和经治患者，他们可能会出现不同的病毒学结果。
方法
这项回顾性研究于2010年至2012年在柬埔寨金边的卡尔梅特医院的HIV诊所进行，评估了初治患者和经治患者的病毒学失败（VF）率及耐药模式。当初治患者在ART的第一年进行病毒载量（VL）检测或经治患者在首次就诊时进行VL检测时，将其纳入研究。出现病毒学失败（VF，>1000拷贝/毫升）的患者接受HIV耐药基因分型检测。根据2013年第23版ANRS算法对耐药突变进行解读。
结果
在总共209名患者中，164名（78.4%）为初治患者，45名（21.5%）为经治患者。他们的初始CD4细胞计数中位数分别为74个细胞/立方毫米（IQR：30 - 194）和279个细胞/立方毫米（IQR：103 - 455）（p<0.001）。27名患者（12.9%）出现病毒学失败（95%CI：8.6 - 18.2%），其中包括10名初治患者（10/164，6.0%）和17名经治患者（17/45，37.8%）（p<0.001）。在这些病毒血症患者中，22名（81.4%）在逆转录酶和蛋白酶编码区进行了测序。总体而言，19名（86.3%）携带≥1种耐药突变（DRM），而3名（均为经治患者）携带野生型病毒。最常见的DRM是M184V（86.3%）、K103N（45.5%）和胸苷类似物突变（TAM）（40.9%）。两名（13.3%）经治患者携带的病毒表现出多核苷酸耐药，包括Q151M、K65R、E33A/D、E44A/D突变。
结论
在柬埔寨，初治患者的病毒学失败率较低，但该亚组中对非核苷类逆转录酶抑制剂（NNRTI）和拉米夫定（3TC）的耐药突变出现相对较快。在经治患者中，病毒学失败率要高得多，TAM相对常见。在开始抗逆转录病毒治疗前以及对于经治患者的感染，也应考虑进行HIV基因分型检测。
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