Efficacy of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies Including Myeloma.

Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO-LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.

Cryptococcal infection in HIV-infected patients with CD4+ T-cell counts under 100/µL diagnosed in a high-income country: a multicentre cohort study.

OBJECTIVES: The World Health Organization recommends routinely screening HIV-infected patients with CD4+ T-cell counts <100/µL for cryptococcal infection to prevent cryptococcal meningitis (CM), based on studies in Sub-Saharan Africa where the prevalence of positive cryptococcal antigen (CrAg+) is ≥ 3% in this subgroup. Data about such prevalence in Spain are unavailable and rare in other European countries. Thus, the Spanish AIDS Study Group guidelines do not recommend routinely screening. We aim to determine the prevalence and outcomes of cryptococcal infection in this subgroup of patients in Spain. METHODS: We determined CrAg using a lateral flow assay in banked plasma from participants in the cohort of the Spanish AIDS Research Network. Eligible patients had CD4+ T-cell counts ≤100/µL at the time of plasma collection and a follow-up >4 weeks, unless they died. RESULTS: We included 576 patients from June 2004 to December 2017. Of these, 43 were CrAg+ for an overall prevalence of 7.5%. There were no differences depending on birthplace. The CrAg+ was independently associated with a higher mortality at eight weeks (hazard ratio (HR) 5.36, 95% confidence interval (CI) 1.46-19.56) and 6 months (HR 3.12, 95% CI 1.19-8.21). CM was reported in 10 of the 43 CrAg+ patients. There were no cases among negatives. Five patients had CM when the plasma was collected and five developed it during the follow-up. The number of subjects needed to screen to anticipate the diagnosis of one CM case was 114. CONCLUSIONS: The CrAg+ prevalence among HIV-infected patients with CD4+ T-cell counts ≤100/µL diagnosed in Spain, both immigrants and native-born Spanish, is >7%. Consequently, the Spanish AIDS Study Group guidelines have to be updated and recommend routine screening for cryptococcal infection in these patients. Future studies should explore whether this recommendation could be firmly applied to other European populations.

A European multicientre study on the comparison of HIV-1 viral loads between VERIS HIV-1 Assay and Roche COBAS® TAQMAN® HIV-1 test, Abbott RealTime HIV-1 Assay, and Siemens VERSANT HIV-1 Assay.

BACKGROUND: Viral load monitoring is essential for patients under treatment for HIV. Beckman Coulter has developed the VERIS HIV-1 Assay for use on the novel, automated DxN VERIS Molecular Diagnostics System.¥ OBJECTIVES: Evaluation of the clinical performance of the new quantitative VERIS HIV-1 Assay at multiple EU laboratories. STUDY DESIGN: Method comparison with the VERIS HIV-1 Assay was performed with 415 specimens at 5 sites tested with COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Test, v2.0, 169 specimens at 3 sites tested with RealTime HIV-1 Assay, and 202 specimens from 2 sites tested with VERSANT HIV-1 Assay. Patient monitoring sample results from 4 sites were also compared. RESULTS: Bland-Altman analysis showed the average bias between VERIS HIV-1 Assay and COBAS HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay to be 0.28, 0.39, and 0.61 log10 cp/mL, respectively. Bias at low end levels below 1000cp/mL showed predicted bias to be <0.3 log10 cp/mL for VERIS HIV-1 Assay versus COBAS HIV-1 Test and RealTime HIV-1 Assay, and <0.5 log10cp/mL versus VERSANT HIV-1 Assay. Analysis on 174 specimens tested with the 0.175mL volume VERIS HIV-1 Assay and COBAS HIV-1 Test showed average bias of 0.39 log10cp/mL. Patient monitoring results using VERIS HIV-1 Assay demonstrated similar viral load trends over time to all comparators. CONCLUSIONS: The VERIS HIV-1 Assay for use on the DxN VERIS System demonstrated comparable clinical performance to COBAS® HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay.