Division of Microbiology, Calgary Laboratory Services, 9-3535 Research Rd. N.W., Calgary, Alberta, Canada.
J Clin Microbiol. 2011 Jan;49(1):118-24. doi: 10.1128/JCM.00685-10. Epub 2010 Nov 17.
HIV clinics in Canada provide care to an increasing number of patients born outside of Canada with HIV-1 non-B subtype infections. Because the Easy Q HIV-1 v1.2 assay (EQ; bioMérieux) failed to detect some non-B subtype infections, a multiassay HIV-1 viral load (VL) study was conducted with patients with diverse HIV subtype infections. Patients were enrolled from the Southern Alberta HIV Clinic (SAC), Calgary, Alberta, Canada (n = 349) and the McGill HIV Clinic (MHC), Montreal, Quebec, Canada (n = 20) and had four or five tubes of blood drawn for testing by EQ and three other commercial HIV VL assays: (i) the Versant 3.0 HIV-1 test, with the Versant 440 instrument (branched DNA [bDNA]; Siemens), (ii) the RealTime HIV-1 test, with the m2000rt instrument (m2000rt; Abbott Molecular Diagnostics), and (iii) the COBAS AmpliPrep TaqMan HIV-1 48 test (CAP-CTM; Roche Molecular Diagnostics). Blood was processed according to the individual manufacturer's requirements and stored frozen at -86°C. The HIV subtype was known for patients who had undergone HIV genotypic resistance testing (Virco, Belgium). Data analyses were done using standard statistical methods within Stata 9.0 (StataCorp, College Station, TX). A total of 371 samples were tested on 369 patients, of whom 291 (81%) had a Virco genotype result of B (195; 53%) or non-B (96; 26%) subtypes A to D and F to K, as well as circulating recombinant forms (CRFs) (i.e., CRF01_AE and CRF02_AG). Most (58/78; 74%) patients of unknown subtype were recent African emigrants who likely have non-subtype B infection. Overall bias was small in pairwise Bland-Altman plots, but the limits of agreement between assays were wide. Discordant viral load results occurred for 98 samples and were due to missing values, false negatives, and significant underquantification that varied by HIV subtype. Results were obtained for all 371 samples with m2000rt, but for only 357 (97%) with CAP-CTM, 338 (92%) with EQ, and 276 (75%) with bDNA due to errors/equipment failures. False-negative results (nondetection of viral RNA versus other assay results) occurred for all platforms, as follows: for m2000rt, 8 (2%) [B(4) and non-B(4) subtypes], CAP-CTM, 9 (2.5%) [B(6) and non-B(3) subtypes]; EQ, 20 (6%) [B(7) and non-B(13) subtypes]; bDNA, 5 (2%) [B(1) and C(4)]. EQ and bDNA had the highest rates of underquantification by ≥ 1.0 log(10) copies/ml, mainly for HIV non-B subtypes. Performance significantly varied between HIV VL platforms according to subtype. HIV viral diversity in the population being tested must be considered in selection of the viral load platform.
加拿大的 HIV 诊所为越来越多的感染 HIV-1 非 B 亚型的加拿大境外出生的患者提供护理。由于 Easy Q HIV-1 v1.2 检测(EQ;bioMérieux)未能检测到一些非 B 亚型感染,因此对具有不同 HIV 亚型感染的患者进行了多检测 HIV-1 病毒载量(VL)研究。患者来自加拿大艾伯塔省卡尔加里的南艾伯塔 HIV 诊所(SAC)(n = 349)和加拿大魁北克省蒙特利尔的麦吉尔 HIV 诊所(MHC)(n = 20),并从四个或五个管血样中抽取用于 EQ 和其他三个商业 HIV VL 检测:(i)Versant 3.0 HIV-1 测试,使用 Versant 440 仪器(分支 DNA [bDNA];西门子),(ii)实时 HIV-1 测试,使用 m2000rt 仪器(m2000rt;雅培分子诊断),和(iii)COBAS AmpliPrep TaqMan HIV-1 48 测试(CAP-CTM;罗氏分子诊断)。血液根据各个制造商的要求进行处理,并储存在-86°C 的冷冻状态。对于接受 HIV 基因型耐药性检测的患者(Virco,比利时),已知 HIV 亚型。使用 Stata 9.0(StataCorp,College Station,TX)内的标准统计方法进行数据分析。在 369 名患者中测试了 371 个样本,其中 291 名(81%)具有已知的 Virco 基因型结果为 B(195;53%)或非 B(96;26%)亚型 A 至 D 和 F 至 K ,以及循环重组形式(CRF)(即 CRF01_AE 和 CRF02_AG)。大多数(58/78;74%)亚类未知的患者是最近的非洲移民,他们可能感染了非 B 亚型。在成对 Bland-Altman 图中总体偏差较小,但各检测之间的协议界限较宽。98 个样本出现了不一致的病毒载量结果,这是由于存在缺失值、假阴性和显著的低估,这些情况因 HIV 亚型而异。所有 371 个样本均获得 m2000rt 的结果,但仅获得 357 个(97%)的 CAP-CTM、338 个(92%)的 EQ 和 276 个(75%)的 bDNA 的结果,这是由于出现错误/设备故障。所有平台均出现假阴性结果(相对于其他检测结果未检测到病毒 RNA),如下所示:m2000rt,8(2%)[B(4)和非 B(4)亚型];CAP-CTM,9(2.5%)[B(6)和非 B(3)亚型];EQ,20(6%)[B(7)和非 B(13)亚型];bDNA,5(2%)[B(1)和 C(4)]。EQ 和 bDNA 的低估率最高(≥1.0 log(10) 拷贝/ml),主要是针对非 B 亚型的 HIV。根据亚型,HIV VL 平台之间的性能差异显著。在选择病毒载量平台时,必须考虑正在检测的人群中的 HIV 多样性。