EVALUATION OF THE ALINITY M HIV-1 ASSAY FOR THE QUANTIFICATION OF HIV-1 RNA PLASMA VIRAL LOAD IN A HIGH-THROUGHPUT MOLECULAR LABORATORY IN SOUTH AFRICA

L. Maree et al
Journal of Clinical Virology, Volume 132, 2020, 104644
Published Online: 18 Sep 2020

This study, conducted at Lancet Labs (South Africa), evaluated the performance of the Alinity m HIV-1 assay versus cobas 4800 and 6800 HIV-1 assays by testing residual sample material and reported:

• Excellent agreement was seen between Alinity and both cobas assays at 200 copies/mL / 1000 copies/mL* (~99% / ~98%) thresholds, while it was slightly lower at 50 copies/mL (c4800: ~93%; c6800: ~91%).
• High correlation and minimal bias between Alinity and cobas results was observed (c4800 [N=961): r=0.98, -0.004 Log10 copies/ml; c6800 [N=389]: r=0.99, 0.22 Log10 copies/mL). 

*WHO threshold

MULTICENTER CLINICAL COMPARATIVE EVALUATION OF ALINITY M HIV-1 ASSAY PERFORMANCE

P. Braun et al
Journal of Clinical Virology, Volume 129, 2020, 104530
Published Online: 03 Jul 2020

The Alinity m HIV-1 Viral Load assay was evaluated in an international multi-center study with 9 participating 9 laboratories. 

• High precision and reproducibility was found with a panel of clinical samples comprising HIV-1 subtypes B, C and CRF02-AG tested across 4 study sites. 
• Alinity m results correlated well with RealTime, Versant kPCR, CAPT/CTM 2.0 and Aptima (range r 0.96 to 0.98). 
• Overall observed bias of Viral Load results was found between Alinity m and the four comparator tests (range -0.10 to 0.10 Log10 copies/mL). 
• Alinity m and comparator tests showed a high level of agreement at clinical decision points of 200 and 50 copies/mL. 

MULTICENTER CLINICAL EVALUATION OF ALINITY M HBV ASSAY PERFORMANCE

S. Bonanzinga et al
Journal of Clinical Virology, Volume 129, 2020, 104514
Published Online: 03 Jul 2020

This paper summarizes the results of the multicenter Alinity m study. 

It demonstrates excellent linearity, precision (SD ≤0.15 Log10 IU/mL; CV 4.1-8.8%), reproducibility (HiPos/ LoPos: SD ≤0.23 Log10 IU/mL; CV ≤6.7%) and a high detection rate around LOD (≥88.9%) of Alinity m HBV. 

With overall 1542 clinical plasma and serum samples, Alinity m HBV showed comparable performance to Abbott RealTime HBV, Roche CAP/CTM HBV v2, Roche cobas 6800 HBV, and Aptima HBV (r≥0.947) with a low mean of bias (range -0.07 to 0.17 Log10 IU/mL). 

No impact of HBV GT A-E was observed.

MULTICENTER CLINICAL EVALUATION OF ALINITY M HCV ASSAY PERFORMANCE

S. Chevaliez et al
Journal of Clinical Virology, Volume 129, 2020, 104531
Published Online: 03 Jul 2020

This paper summarizes the results of the multicenter Alinity m study. 

It demonstrates excellent linearity, precision (SD ≤0.21 Log10 IU/mL; CV 6.6-13.5%), reproducibility (HiPos/LoPos: SD ≤0.12 Log10 IU/mL; CV ≤4.3%) and a high detection rate at 25 IU/mL (≥98.3%) of Alinity m HCV. 

With overall 1807 clinical plasma and serum samples, Alinity m HCV showed comparable performance to Abbott RealTime HCV, Roche cobas 6800 HCV, and Aptima HCV (r≥0.959) with a low bias (range -0.01 to 0.14 Log10 IU/mL). 

No impact of HCV GT 1-6 was observed.

CLINICAL AND ANALYTICAL EVALUATION OF THE ALINITY M HR HPV ASSAY WITHIN THE VALGENT-3 FRAMEWORK

SK. Dhillon et al
Juornal of Clinical Microbiology, Volume 59, 6 e00286-21. 
Published Online: 19 May 2021

This study evaluated the Alinity m HR HPV assay in comparison to alternative tests using the VALGENT III panel, consisting of 1,300 consecutive cervical samples from women attending organized population-based cervical screening, enriched with 300 samples from women with abnormal cytology.

• Compared to HC2, relative sensitivity for CIN2+/CIN3+ of Alinity m (1.02 [0.99–1.06]/1.03 [0.99–1.06] and its relative specificity for ≤CIN1 (1.01 [1.00–1.02]) were slightly higher.
• Clinical sensitivity and specificity of Alinity m were non-inferior to HC2, RealTime HR HPV and cobas 4800 for the entire study population and among women of ≥30 years.
• HPV genotype-specific concordance between Alinity m and the comparator tests showed excellent agreement (kappa values: 0.82 and 1.00).

COMPARISON OF THE CLINICAL AND ANALYTICAL PERFORMANCE OF ALINITY M HR HPV AND COBAS 4800 HPV ASSAYS IN A POPULATION-BASED SCREENING SETTING

A. Oštrbenk Valenčak et al
Journal of Clinical Virology, Volume 140, July 2021, 104851
Published Online: 10 May 2021

This study compared the performance of Alinity m HR HPV with cobas 4800 and reports:

• Similar clinical performance and cobas 4800 HPV assay (no statistically significant differences in clinical sensitivity & specificity in women of ≥30 years)
• Excellent overall agreement for HPV genotype detection (overall agreement 97.9% [HPV16: 99.6%; HPV18: 99.8%; other hrHPV: 98.1%]).

Cohort (N=4400) data analysis provides evidence that extended genotyping with of Alinity m HR HPV could significantly reduce referral rates of women in need of 6-12 months follow up versus cobas 4800 (224 [5.0%] vs. 378 [8.6%]; p <0.0001).

2020 LIST OF HUMAN PAPILLOMAVIRUS ASSAYS SUITABLE FOR PRIMARY CERVICAL CANCER SCREENING

M. Arbyn et al
Journal of Clinical Microbiology and Infection 2021 May 8;S1198-743X(21)00219-6. 
Published Online: 8 May 2021

This meta-analysis by a consortium of international KOLs (Europe, US, APAC) reviewed published HPV test validation studies designed following Meijer Guidelines 2009 to update the list of HR HPV DNA tests suitable for screening established in 2015:

Both, Alinity m and RealTime HR HPV assays range among the eleven HPV DNA tests considered fully clinically validated.

COMPARISON BETWEEN ABBOTT M2000 REALTIME AND ALINITY M STI SYSTEMS FOR DETECTION OF CHLAMYDIA TRACHOMATIS, NEISSERIA GONORRHOEAE, AND MYCOPLASMA GENITALIUM

B. Hermann et al
European Journal of Clinical Microbiology & Infectious Diseases
Published Online: 15 March 2021

This study compared Alinity m STI CT/NG/MG results to RealTime CT/NG and MG PCRs (home-brew), testing urogenital and extragenital specimens collected in Alinity and m2000 Multi-Collect tubes used in alternating fashion from patients attending an STI clinic for suspected CT/NG/MG infections:

• Agreement between Alinity & RealTime results (347 matched samples): 98.8% for CT and 98.3% for NG.
• Sensitivity & specificity for CT and NG of the Alinity: 95.8% & 99.1% and 100% & 98.2%.
• MG positivity was higher with Alinity compared to inhouse PCR (279 matched samples): 7.9% vs 6.5% (agreement 97.8%), suggesting higher sensitivity of the Alinity assay. In addition, MG presence in another 167 Alinity positive samples was confirmed with Diagenode MG PCR (remaining 8 samples had high Ct values with Alinity m).
• No TV positives were identified in the study population.

SECOND- AND THIRD-GENERATION COMMERCIAL NEISSERIA GONORRHOEAE SCREENING ASSAYS AND THE ONGOING ISSUES OF FALSE-POSITIVE RESULTS AND CONFIRMATORY TESTING

TM. Pryce et al
European Journal of Clinical Microbiology & Infectious Diseases 2021 Jan;40(1):67-75.
Published Online: 07 August 2020

This study investigated NG confirmation rates of cobas 4800 and RealTime CT/NG assays applying an expanded gold standard on NG positives (344 multi-collect samples; 744 cobas PCR media samples): All samples were tested with an in-house duplex NG PCR (opa & por-A). In addition, 344 cobas samples were also tested with RealTime and Xpert and 400 cobas samples were tested with cobas 6800. Culture results from inhouse duplex NG PCR-negative samples (extra-genital) were also considered, when available.

The NG confirmation rate for RealTime results (98%) was higher than that of both cobas 4800 series (92.7% and 93.2%) and exceeded 90% for all anatomical sites, with the exception of 78% for oropharyngeal specimens tested with cobas 4800.

COMMERCIALLY AVAILABLE MOLECULAR TESTS FOR HUMAN PAPILLOMAVIRUSES: A GLOBAL OVERVIEW

M. Poljak et al
Clinical Microbiology and Infection, Volume 26, 2020, 1144e1150
Published Online: 02 April 2020

This overview of marketed HPV tests reports a total of 254 distinct assays being available globally. The author ranked tests along their validation (Meijer Guidelines, VALGENT framework) and approval status (FDA; WHO pre-qualification) [see supplemental data]. 

Abbott RealTime and Alinity m HR HPV rank among the few tests validated for cervical cancer screening (Meijer & VALGENT), while RealTime is also WHO pre-qualified. 

RealTime, HC2, cobas 4800, Onclarity and Xpert fulfil three criteria, while none of the tests fulfill all four criteria. 

VALIDATION AND VERIFICATION OF THE ABBOTT REALTIME SARS-COV-2 ASSAY ANALYTICAL AND CLINICAL PERFORMANCE

E. Degli-Angeli et al
Journal of Clinical Virology, Volume 129, 2020, 104474
Published Online: 28 May 2020

This paper demonstrates the high sensitivity (93%) and specificity (100%) of the FDA EUA Abbott RealTime SARS-CoV-2 assay. 

Detection rate exceeded LOD (95% at 50 copies/mL). 24 non-SARS-CoV-2 samples were negative.

In comparison to a CDC-based in-house assay, 100% specificity and 93% sensitivity was observed (the two discordant positive samples had late cycle numbers, including one with inconclusive results in addition, were diluted 1:2 and subsequently found negative with m2000).

PERFORMANCE CHARACTERISTICS OF THE ABBOTT ALINITY M SARS-COV-2 ASSAY

GA. Perchetti et al
Journal of Clinical Virology, Volume 140, July 2021, 104869
Published Online: 14 May 2021

This paper demonstrates the good assay performance of Alinity m SARS-CoV-2 vs. Roche cobas 6800 and Hologic Panther Fusion in nasopharyngeal swabs. Overall agreement was 100% with Panther Fusion, while compared to c6800, Alinity detected 8 samples as positive that were either negative (n=1), only presumptive positive (n=5; only sarbecovirus target positive) or only positive by the SARS-CoV-2 target (n=2). Alinity m SARS-CoV-2 showed high sensitivity (100% detection rates at 50 cp/ml), specificity (no detection of nonSARS-CoV-2 viruses), linearity (R²>0.99), and agreement between two Alinity m instruments (0.4 Ct difference). Precision (CVs<2%;PPA/NPA=100%) was higher with Alinity m than LDT (CV<3%).

CAVE: Non-CE-marked assays

VERIFICATION OF THE ABBOTT ALINITY M RESP-4-PLEX ASSAY FOR DETECTION OF SARS-COV-2, INFLUENZA A/B, AND RESPIRATORY SYNCYTIAL VIRUS

A. Cheng et al
MediRxiv 2021 April. 
Published Online: 22 April 2021

This reprint demonstrates how Alinity m Resp-4-Plex assay is a welcome addition to targeted respiratory panel options that will be necessary in a post-COVID world when the signs and symptoms of respiratory diseases overlap.  It appeared highly accurate, sensitive and precise in detecting SARS-CoV-2, influenza A, influenza B and RSV.  

Data showed that clinical samples that were identified as positive by other assays were positive by Alinity m Resp-4-Plex.  Good agreement with other assays.

In influenza B positive samples, Alinity m Resp-4-Plex detected RSV positive which was missed by comparator assay. 

VERIFICATION AND VALIDATION OF SARS-COV-2 ASSAY PERFORMANCE ON THE ABBOTT M2000 AND ALINITY M SYSTEMS (FDA EUA)

JW. Hirschhorn et al
Journal of Clinical Microbiology 2021 Apr 20;59(5):e03119-20.
Published Online: 20 April 2021

This paper demonstrates the analytical performance of the FDA EUA Abbott RealTime SARS-CoV-2: linearity: R²=0.99; reproducibility: CV<5%; confirmed LOD=100 cp/ml; no cross reaction with common respiratory pathogens.

Data showed good clinical performance compared to the CDC (91% PPA, 100% NPA) and ThermoFisher TaqPath assays (100% PPA, 95% NPA). Furthermore, authors confirmed LOD=100 cp/ml for Alinity m SARS-CoV-2 and demonstrated equivalent clinical performance with RealTime SARS-CoV-2 (PPA and NPA ≥92%).

Frequency distribution of Cn values of first positive clinical specimens revealed 8% of specimens with low viral burdens (<100 cp/ml) which can only be detected with a highly sensitive assay.

COMPARATIVE ANALYSIS OF POINT-OF-CARE, HIGH-THROUGHPUT AND LABORATORY-DEVELOPED SARS-COV-2 NUCLEIC ACID AMPLIFICATION TESTS (NATS)

N. Kohmer et al
Journal of Virologic Methods Volume 291, May 2021, 114102
Published Online: 16 February 2021

This paper to demonstrate the excellent sensitivity of the Alinity m SARS-CoV-2 assay compared toa number of alternative assays. Alinity m detected very low Viral Loads s of a dilution panel or an INSTAND EQA panel.

DIAGNOSTIC ACCURACY OF CENTRALISED ASSAYS FOR TB DETECTION AND DETECTION OF RESISTANCE TO RIFAMPICIN AND ISONIAZID: A SYSTEMATIC REVIEW AND META-ANALYSIS

M. Kohli et al
The European Respiratory Journal, 57(2), 2000747
Published Online: 04 Feb 2021

This manuscript highlights FIND's systematic review of new centralized molecular assays for MTB and RIF/INH resistance.

• Data pool from previously published studies was significantly larger for RealTime versus comparator tests. 
• Pooled estimates for KPIs of RealTime were comparable to those of the other tests. 
• Since all three tests demonstrated sensitivity for smear-negative cases comparable to Xpert MTB/RIF, they are rated as “good contenders for this frequently difficult-to-diagnose use case” by the authors. 
• m2000 platform has a broad menu among other systems and a higher throughput versus BD Max (24 per run).

COMPARATIVE ANALYTICAL EVALUATION OF FOUR CENTRALIZED PLATFORMS FOR THE DETECTION OF M. TUBERCULOSIS COMPLEX AND RESISTANCE TO RIFAMPICIN AND ISONIAZID

M. de Vos et al
Journal of Clinical Microbiology, 2020, JCM.02168-20
Published Online: 02 Dec 2020

This study by FIND, assessed analytical sensitivity for MTBc and accuracy for RIF/INH detection of centralized tests using M.tuberculosis and M.bovis strains spiked into sputum and strains with high-confidence mutations accounting for >85% of first-line resistance globally: 

• RealTime MTB demonstrated high sensitivity for H37Rv (322 genomes/mL), compared to BD MAX MDR-TB (826 genomes/mL), Roche cobas MTB (2,416 genomes/mL), Xpert (3,781 genomes/mL) and Hain FluoroType MTBDR (10,398 genomes/mL). 
• RealTime and Roche MTB assays had higher and similar sensitivity for M. bovis (2,182 / 2,136 genomes/mL), compared to Xpert (2,926 genomes/mL), BD (4,301 genomes/mL) and Hain (23,139 genomes/mL). 

THE PERFORMANCE OF THE ABBOTT REAL TIME MTB RIF/INH COMPARED TO THE MTBDR PLUS V2 FOR THE IDENTIFICATION OF MDR-TB AMONG ISOLATES

A. David et al
Infection and Drug Resistance, Volume 13, 2020, 3301-3308
Published Online: 28 Sep 2020

This study conducted at WITS/NHLS, South Africa compared the RealTime MTB Resistance assay with Hain MTBDRplus v2 (LPA) on 93 cultured isolates, of which 83 generated successful results with both tests.

• RealTime showed high agreement for resistance detection with LPA (RIF, k: 0.765; INH, k: 0.919). 
• Sequencing of 10 samples with discordant resistance results revealed a lower resistance misclassification rate with RealTime (2 RIF, 4 INH) compared to LPA (6 RIF, 3 INH).