A study with individuals who inject drugs evaluated a minimally invasive test based on dried blood spots (DBS) for the monitoring of hepatitis C virus (HCV) infection. The usage of DBS samples for HCV RNA detection and genotyping was shown to effectively assess cure after treatment and to distinguish between reinfection and treatment failure. The outcomes support the viability of decentralizing treatment and post-treatment monitoring for individuals who inject drugs, who regularly face challenges accessing the healthcare system. The study, which has been published within the Journal of Medical Virology, was carried out as a part of a project with support from the “Conquering Hepatitis Via Microelimination” (CHIME) programme and a PFIS grant. Investigators from various research institutions collaborated within the project, including the Clinical Virology and Recent Diagnostic Tools research group, led by Dr Elisa Martró, at Germans Trias i Pujol Research Institute (IGTP) and Dr Sabela Lens from Hospital Clínic’s Viral Hepatitis Group.

Towards elimination of hepatitis

In keeping with the strategy proposed by the World Health Organization for the elimination of viral hepatitis as a public health threat by 2030, and the Plan for Prevention and Control of Hepatitis in Catalonia, which Dr Martró actively participates in, her group has been focused for years on simplifying the diagnosis of hepatitis C by developing and validating an assay which may detect the virus RNA using DBS samples. These minimally invasive samples may be collected at harm reduction centres or drug dependence care and follow-up centers (often called CAS in Catalan), improving access to hepatitis C diagnosis for vulnerable populations, akin to individuals who inject drugs. While this latest test has demonstrated good clinical performance as a diagnostic tool for detecting HCV RNA before treatment in previous studies by the Clinical Virology and Recent Diagnostic Tools research group, using DBS samples had not been evaluated as a test for cure or for detecting reinfection after treatment.

A multidisciplinary research group has been in a position to pursue a project with a latest model of take care of hepatitis C, based on point-of-care diagnosis, treatment, and reinfection follow-up on the REDAN La Mina harm reduction centre. Since 2019, roughly 750 individuals who inject drugs have been tested though this initiative, which was designed by Dr Sabela Lens from Hospital Clínic’s Viral Hepatitis Unit, in collaboration with the Clinical Virology and Recent Diagnostic Tools Research Group at Germans Trias i Pujol Research Institute (IGTP), led by Dr Martró from the Microbiology Service (LCMN) of the Germans Trias i Pujol Hospital (HUGTiP), in addition to CEEISCAT and the Public Health Agency of Catalonia. The project had the support of the “Conquering Hepatitis Via Microelimination” (CHIME) programme from Gilead Sciences awarded to Dr Lens, in addition to a PFIS grant of the Instituto de Salud Carlos III and the Fondo Social Europeo awarded to Anna Not, who’s a member of Dr Martró’s group, and aligns with the World Health Organization’s global health strategy, which goals to eliminate hepatitis C as a public health problem by 2030.

A model of decentralized care

On this project, Dr Martró’s group aimed to guage the clinical performance of a previously developed HCV-RNA assay based on DBS, for the assessment of cure and the detection of recurrent viremia after on-site treatment on the harm reduction center, in comparison with the commercially available HCV-RNA point-of-care test. Moreover, they sought to evaluate the opportunity of distinguishing between reinfection and treatment failure through HCV genotyping from baseline and follow-up DBS samples. Typically, these assessments (cure and reinfection) are performed using venipuncture blood samples collected at healthcare centres, which may be difficult for individuals who inject drugs and have often limited access to the healthcare system. The recently published results exhibit how the gathering of DBS samples before and after treatment can simplify these assessments in decentralized test-and-treat programmes.

“The success of the CHIME project lies within the decentralized diagnosis and treatment provided at REDAN La Mina. A nurse trained in hepatology assessments was included within the study to enrol and visit participants. The hepatologists at Hospital Clínic also reviewed each case and prescribed decentralized treatment. Moreover, Dr Martró’s group carried out HCV detection and sequencing from DBS samples collected before and after treatment. This pilot program involves HCV diagnosis on-site in lower than an hour, treatment at the identical center, and follow-up to evaluate reinfection”, states Dr Lens.

Detection made easier

Reinfection is common in individuals who inject drugs and should be treated to forestall further transmission of the virus. During early reinfection, low levels of the virus could also be present, making its detection in DBS samples difficult, as they only contain a small amount of blood. Of the 193 DBS samples tested after treatment, the DBS-based assay showed 100% specificity and sensitivity starting from 84% to 96% based on different relevant viral load cut-offs, and similar rates as a test of cure (three months after treatment). It should be born in mind that among the many patients with recurrent viremia after treatment, one tenth had low viral loads. Furthermore, HCV genotyping allowed researchers to categorise 73% of viremic cases as either reinfection or treatment failure.

Collection of DBS samples was done before antiviral treatment and after treatment if recurrent viremia was detected by the commercially available point-of-care assay. Anna Not, the primary creator of the article (which might be a part of her PhD), explains that it “using DBS allowed us to sequence the virus before and after treatment and compare the sequences to find out if the virus was the identical (indicating a treatment failure) or if it was different (indicating reinfection). This information enabled the hepatologist to make your mind up on probably the most appropriate antiviral combination for the second treatment”.

The research shows the potential of using DBS samples for determining cure and differentiating between reinfection and relapse after antiviral treatment for hepatitis C in individuals who inject drugs. The usage of DBS samples makes it possible to decentralize treatment and follow-up, improving access to take care of these people. Even so, Dr Martró points out that “a small variety of patients had low viral loads, which may hinder the detection of viremia and genotyping in DBS. Consequently, repeat testing (e.g. every six months) is suggested for people who’re liable to HCV reinfection”.

Source:

Germans Trias i Pujol Research Institute

Journal reference:

Not, A., et al. (2023) Usefulness of dried blood spot samples for monitoring hepatitis C treatment end result and reinfection amongst individuals who inject drugs in a test-and-treat program. Journal of Medical Virology. doi.org/10.1002/jmv.28544.