Hepatitis C virus infection associated with coronary and thoracic aortic atherosclerosis.

BACKGROUND: Coronary and thoracic aortic calcification was associated with stroke, coronary heart, and peripheral vascular disease. Hepatitis C virus (HCV) infection is significantly associated with insulin resistance, diabetes mellitus and hepatic steatosis. We aimed to investigate the relationship between HCV infection and coronary, thoracic aortic atherosclerosis. MATERIALS AND METHODS: Calcification was detected by chest computed tomography and defined as any Agatston score greater than zero. Metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Fibrosis-4 (FIB-4) and AST-to-platelet ratio (APRI) was calculated. The anti-HCV signal-to-cutoff (S/CO) ratio was determined by the third generation ELISA kit. Atherosclerosis risk was estimated by using multiple logistic regression modeling. RESULTS: Being positive for both metabolic syndrome and HCV infection (OR = 2.65, 95% CI: 1.26-5.59, p = 0.007), negative for metabolic syndrome and positive for HCV infection (OR = 2.75, 95% CI: 1.48-5.30, p = 0.001), and positive for metabolic syndrome and negative for HCV infection (OR = 2.42, 95% CI: 1.92-3.07, p < 0.001) were associated with atherosclerosis compared with being negative for both metabolic syndrome and HCV infection (Ptrend< 0.001). HCV infection with liver fibrosis (HCVFIB4>1.4; OR = 2.16, 95% CI: 1.22-3.82, p = 0.008), or (HCVAPRI>0.5; OR = 3.40, 95% CI: 1.28-9.06, p = 0.014) and elevated anti-HCV S/CO ratio (anti-HCVS/CO>10.0; OR = 1.72, 95% CI: 1.01-2.93, p = 0.045) was associated with atherosclerosis. CONCLUSIONS: HCV infection with metabolic syndrome, liver fibrosis and elevated anti-HCV S/CO ratio was associated with atherosclerosis.

Using signal-to-cutoff ratios of HIV screening assay to predict HIV infection.

BACKGROUND: The sensitivity of HIV screening assays often leads to a high rate of false-positive results, requiring retests and confirmatory tests. This study aimed to analyze the capability of signal-to-cutoff (S/CO) ratios of HIV screening assay to predict HIV infection. METHODS: A retrospective study on the HIV screening-positive population was performed at Zhongshan Hospital, Xiamen University, the correlation between HIV screening assay S/CO ratios and HIV infection was assessed, and plotted Receiver Operating Characteristic (ROC) curves were generated to establish the optimal cutoff value for predicting HIV infection. RESULTS: Out of 396,679 patients, 836 were confirmed to be HIV-infected, with an HIV prevalence of 0.21%. The median S/CO ratios in HIV infection were significantly higher than that in non-HIV infection (296.9 vs. 2.41, P < 0.001). The rate of confirmed HIV infection was increased with higher S/CO ratios in the screening assay. The ROC curve based on the HIV screening assay S/CO ratio achieved a sensitivity of 93.78% and a specificity of 93.12% with an optimal cutoff value of 14.09. The area under the ROC curve was 0.9612. Further analysis of the ROC curve indicated that the S/CO ratio thresholds yielding positive predictive values of 99%, 99.5%, and 100% for HIV infection were 26.25, 285.7, and 354.5, respectively. CONCLUSION: Using HIV screening assay S/CO ratio to predict HIV infection can largely reduce necessitating retests and confirmatory tests. Incorporating the S/CO ratio into HIV testing algorithms can have significant implications for medical and public health practices.

A case of a false positive HIV antigen/antibody screen in a pregnant woman at delivery and the clinical importance of reviewing signal-to-cutoff ratio values.

We present a unique case not previously touched upon in the literature, and its ensuing management, of a falsely reactive HIV (human immunodeficiency virus) screening test which resulted in a woman during active labor, hours after rupture of membranes. The patient was screened for HIV using the ARCHITECT 4th generation HIV 1 and 2 Antigen/Antibody (Ag/Ab) Combo assay, and the results were repeatedly reactive. A cesarean delivery was recommended, and the patient received intrapartum antiretroviral therapy. Due to rapid progression of labor, the infant was delivered vaginally and received multiple doses of antiretroviral therapy. For confirmation, a viral load PCR test was obtained which resulted undetectable, and it was concluded that the screening results were falsely positive. While the cause of the inaccurate screening result is still unclear, a COVID-19 vaccination in close proximity to the delivery remains suspicious. Four months after delivery, the patient's screening test was no longer reactive.

Improved detection of hepatitis C virus-positive blood donors and determination of infection status.

BACKGROUND: In low-risk populations, variability in the sensitivity of current serological tests for Hepatitis C virus (HCV) blood donor screening may lead to the presence of false-positive results. This contributes to the unnecessary loss of blood donor samples as well as to difficulty in accurate donor counselling. The present study determined the optimal cut-off value of a chemiluminescent immunoassay for identification of HCV-reactive blood donors. STUDY DESIGN AND METHODS: In a retrospective cross-sectional analysis of 193 973 blood donations, 578 samples that were positive for HCV antibody in a chemiluminescent immunoassay and/or RNA screening tests were identified. Blood from 379 of these positive samples was available for retesting by a second confirmatory HCV immunoassay followed by a receiver operating characteristic (ROC) curve analysis. Donors were also recalled for a new analysis. RESULTS: Only 71 (18.7%) blood samples remained HCV-positive upon retesting, while 233 (61.5%) now tested negative and 75 (19.8%) yielding indeterminate results. A signal to cutoff ratio ≥4.32 was determined as the best differential threshold between a positive and negative result, increasing the positive predictive value from 27.3% to 66.7%. CONCLUSION: Using a higher threshold for an HCV-positive blood sample enhances the chemiluminescent immunoassay screening test´s accuracy and helps to improve donor counselling and notification processes.

Novel Criteria for Diagnosing Acute and Early Human Immunodeficiency Virus Infection in a Multinational Study of Early Antiretroviral Therapy Initiation.

BACKGROUND: Antiretroviral therapy (ART) initiation during acute and early human immunodeficiency virus infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of AEHI diagnostic criteria from a prospective study of early ART initiation. METHODS: AIDS Clinical Trials Group A 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any 1 of 6 criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Ag/Ab Combo or GS HIV Combo Ag/Ab EIA. HIV status and Fiebig stage were confirmed by centralized testing. RESULTS: From 2017 through 2019, 195 participants were enrolled with median age of 27 years (interquartile range, 23-39). Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, 4 (2.0%) participants were found to have chronic infection, and 3 (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II-IV AEHI cases with no false-positive results. CONCLUSIONS: Novel AEHI criteria that incorporate ARCHITECT S/CO facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice. CLINICAL TRIALS REGISTRATION: NCT02859558.

Signal-to-cutoff ratios of current anti-HCV assays and a suggestion of new algorithm of supplementary testing.

BACKGROUND: The detection of hepatitis C virus antibody (anti-HCV) is known to have high false-positive rates. Using signal-to-cutoff (S/Co) ratios in reflex supplemental testing, however, could reduce false-positive rates. Here, we analyzed the 2-year data of an anti-HCV assay to understand the significance of the S/Co ratio and make a new algorithm by confirming with a second anti-HCV assay. METHODS: We reviewed 32,573 samples of the Architect assay (Abbott Diagnostics) from a tertiary hospital. Retests with the Elecsys (Roche Diagnostics) and Vitros (Ortho Clinical Diagnostics) assays were performed in 346 anti-HCV-positive samples. HCV RNA PCR and recombinant immunoblot assay (RIBA) were performed in 147 and 11 anti-HCV-positive samples, respectively. RESULTS: Among 32,573 samples, 446 (1.37%) yielded positive results and 32,127 (98.6%) yielded negative results. Concordance rates in low S/Co samples (0.9-10.0) were 35.2%, 43.8%, and 81.9% for the Architect-Elecsys, Architect-Vitros, and Elecsys-Vitros comparisons, respectively. Correlation coefficients of S/Co ratios were as follows: Architect-Elecsys, 0.20; Architect-Vitros, 0.42; and Elecsys-Vitros, 0.46. In logistic regression, the S/Co value for predicting positivity with 95% probability was 3.13, while that for predicting 50% probability was 8.85. S/Co ratios of 1.70-3.34 showed one reactive antigen out of five antigens, and S/Co ratios of 13.54-17.72 showed three to five positive reactions out of five antigens used in the RIBA. CONCLUSIONS: Supplementary testing of anti-HCV screening results is necessary to distinguish between true positivity and biological false positivity for anti-HCV. In this study, we presented an algorithm of supplementary testing by a retest with a second reagent, which could be useful in clinical laboratories.

HIV serology signal-to-cutoff ratio as a rapid method to predict confirmation of HIV infection.

Early and rapid detection of patients with HIV is a key to preventing further transmission. The purpose of this study was to assess the ability of signal-to-cutoff (S/CO) ratio from initial screening fourth-generation HIV serology to predict subsequent confirmation of HIV. Patients with a first-time positive HIV serology (S/CO ratio ≥ 1) from 2012 to 2016 were included. Ratios were compared to the results of confirmatory testing. Predictive probabilities (PPs) of a positive confirmatory result were calculated based on a logistic regression model. A total of 45,138 HIV serology tests were performed; 250 patients met inclusion criteria, comprising 84 (34%) HIV negative patients, 136 (54%) chronic infections, and 30 (12%) acute infections. The PP of a confirmed positive result increased with higher S/CO ratios, with a PP of 100% for a S/CO of 55 (95% CI 95-100). This study enables a more informed discussion of the probability of HIV infection, based on HIV serology S/CO thresholds, prior to a confirmatory result.

The Role of the Signal-to-Cutoff Ratio in Automated Anti-HCV Chemiluminescent Immunoassays by Referring to the Nucleic Acid Amplification Test and the Recombinant Immunoblot Assay.

BACKGROUND: Following discontinuation of the recombinant immunoblot assay (RIBA), the only available supplementary test for the detection of hepatitis C virus (HCV) is the nucleic acid amplification test (NAAT). However, the NAAT does not adequately detect past HCV. Consequently, it is hard to distinguish between past HCV infection and biological false positivity with an anti-HCV result alone. We assessed the diagnostic performance of two immunoassays: the ARCHITECT anti-HCV chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, Wiesbaden, Germany) and the Access HCV Ab PLUS chemiluminescent immunoassay (CIA; Bio-Rad, Marnes-la-Coquette, France). We also explored an optimized algorithm to determine the anti-HCV results. METHODS: We tested 126,919 patients and 44,556 individuals who underwent a medical checkup. RIBA and NAAT were conducted for samples that tested anti-HCV-positive using CMIA and CIA. We assessed the optimal signal-to-cutoff (S/CO) ratio in HCV-positive samples. RESULTS: In total, 1,035 blood samples tested anti-HCV-positive. Of these, RIBA was positive in 512, indeterminate in 160, and negative in 363 samples. One hundred sixty-five samples were NAAT-positive. Diagnostic sensitivity and positive predictive value (PPV) were 96.7% and 52.1%, respectively, for CMIA, and 94.7% and 72.3%, respectively, for CIA. The optimal S/CO ratio was 5.2 for CMIA and 2.6 for CIA at 95% PPV. In total, 286 samples tested positive in CMIA and 444 in CIA, while 443 samples tested positive in both assays. CONCLUSIONS: It is hard to determine anti-HCV positivity based on the S/CO ratio alone. However, this study elucidated the role of the S/CO ratio by using the NAAT and RIBA.

The Role of the Signal-to-Cutoff Ratio in Automated Anti-HCV Chemiluminescent Immunoassays by Referring to the Nucleic Acid Amplification Test and the Recombinant Immunoblot Assay

BACKGROUND: Following discontinuation of the recombinant immunoblot assay (RIBA), the only available supplementary test for the detection of hepatitis C virus (HCV) is the nucleic acid amplification test (NAAT). However, the NAAT does not adequately detect past HCV. Consequently, it is hard to distinguish between past HCV infection and biological false positivity with an anti-HCV result alone. We assessed the diagnostic performance of two immunoassays: the ARCHITECT anti-HCV chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, Wiesbaden, Germany) and the Access HCV Ab PLUS chemiluminescent immunoassay (CIA; Bio-Rad, Marnes-la-Coquette, France). We also explored an optimized algorithm to determine the anti-HCV results. METHODS: We tested 126,919 patients and 44,556 individuals who underwent a medical checkup. RIBA and NAAT were conducted for samples that tested anti-HCV-positive using CMIA and CIA. We assessed the optimal signal-to-cutoff (S/CO) ratio in HCV-positive samples. RESULTS: In total, 1,035 blood samples tested anti-HCV-positive. Of these, RIBA was positive in 512, indeterminate in 160, and negative in 363 samples. One hundred sixty-five samples were NAAT-positive. Diagnostic sensitivity and positive predictive value (PPV) were 96.7% and 52.1%, respectively, for CMIA, and 94.7% and 72.3%, respectively, for CIA. The optimal S/CO ratio was 5.2 for CMIA and 2.6 for CIA at 95% PPV. In total, 286 samples tested positive in CMIA and 444 in CIA, while 443 samples tested positive in both assays. CONCLUSIONS: It is hard to determine anti-HCV positivity based on the S/CO ratio alone. However, this study elucidated the role of the S/CO ratio by using the NAAT and RIBA.

Clinical performance of the novel DiaSorin LIAISON(®) XL murex: HBsAg Quant, HCV-Ab, HIV-Ab/Ag assays.

BACKGROUND: The fully automated and closed LIAISON(®)XL platform was developed for reliable detection of infection markers like hepatitis B virus (HBV) surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Ab) or human immunodeficiency virus (HIV)-Ag/Ab. To date, less is known about the diagnostic performance of this system in direct comparison to the common Abbott ARCHITECT(®) platform. OBJECTIVES: We compared the diagnostic performance and usability of the DiaSorin LIAISON(®)XL with the commonly used Abbott ARCHITECT(®) system. STUDY DESIGN: The qualitative performance of the above mentioned assays was compared in about 500 sera. Quantitative tests were performed for HBsAg-positive samples from patients under therapy (n=289) and in vitro expressed mutants (n=37). For HCV-Ab, a total number of 155 selected samples from patients chronically infected with different HCV genotypes were tested. RESULTS: The concordance between both systems was 99.4% for HBsAg, 98.81% for HCV-Ab, and 99.6% for HIV-Ab/Ag. The quantitative LIAISON(®)XL murex HBsAg assay detected all mutants in comparable amounts to the HBsAg wild type and yielded highly reliable HBsAg kinetics in patients treated with antiviral drugs. Dilution experiments using the 2nd International Standard for HBsAg (WHO) showed a high accuracy of this test. HCV-Ab from patients infected with genotypes 1-3 were equally detected in both systems. Interestingly, S/CO levels of HCV-Ab from patients infected with genotype 3 seem to be relatively low using both systems. CONCLUSIONS: The LIAISON(®)XL platform proved to be an excellent system for diagnostics of HBV, HCV, and HIV with equal performance compared to the ARCHITECT(®) system.