RESUMEN
BACKGROUND: Modern assays for the detection of Chlamydia trachomatis (CT) rely on nucleic acid amplification testing (NAAT) of DNA or ribosomal RNA. However, it is also known that both viable ("living") & non-viable ("dead") CT can be detected by NAAT. Multiple laboratory techniques to measure CT viability have emerged. METHODS: We searched PubMed, EMBASE, Scopus and Dimensions as well as conference abstracts for entries between January 2000 to May 2023. We included any studies that measured CT viability among NAAT-positive samples. Viability assays include enhanced cell culture, direct fluorescent antibody (DFA), messenger RNA (mRNA) detection via digital droplet PCR (ddPCR), viability PCR (V-PCR) & real-time PCR measuring RNA-to-DNA ratio (RDR) (e.g. InSignia®). A meta-analysis was performed on the proportions of non-viable CT by anatomical site. RESULTS: We screened 31,342 records and included 16 studies in the analysis. The pooled proportions of non-viable CT by site were: 33% (95%CI 19-47%) in rectal swabs (eight studies), 17% (95%CI 7-27%) in cervical swabs (six studies), 15% (95%CI 6-25%) in vaginal swabs (six studies) and 11% (95%CI 9-17%) in urine/urethral swabs (two studies). CONCLUSION: All included studies found that a proportion of NAAT-detected CT is non-viable. The findings have far-reaching implications for screening programs and studies evaluating new STI tests and antimicrobial regimens.
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HIV self-testing allows people to collect samples and test themselves at home, addressing known barriers to facility-based testing. We aimed to measure the uptake of home HIV testing among Australian gay and bisexual men (GBM). Using national cross-sectional data from the Australian Gay Community Periodic Surveys, we assessed trends in home HIV testing among non-HIV positive GBM between 2018 and 2020. Overall, the use of home HIV testing was low, but slightly increased during 2018-2020 (from 0.3 to 0.8%, RR = 1.54, 95%CI = 1.23-1.92, p-trend < 0.001). Testing at home was more likely among non-HIV-positive GBM who were born overseas and recently arrived in Australia, at higher risk of HIV, and infrequent HIV testers. Given the greater use of home testing by men at higher risk of HIV, recent migrants and infrequent testers, all priority groups in Australia's HIV epidemic, we recommend increasing access to HIV self-testing to enhance uptake in these and other groups of GBM.
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Infecciones por VIH , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Estudios Transversales , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Australia/epidemiología , Bisexualidad , Prueba de VIHRESUMEN
BACKGROUND: Simplified diagnostic strategies are needed increase hepatitis C virus (HCV) testing to determine active infection and link people into treatment. Collection methods such as dried blood spots (DBS) have advantages over standard phlebotomy, especially within marginalized populations. METHODS: We evaluated the diagnostic performance of the Aptima HCV Quant assay for the quantification and detection of HCV RNA from paired DBS and venepuncture samples. Specimens were collected from participants enrolled in an Australian observational study. We compared HCV RNA detection from DBS against venepuncture samples (gold standard). RESULTS: One hundred sixty-four participants had paired samples and HCV RNA was detected in 45 (27% [95% confidence interval, 21%-35%]) by the Aptima assay in venepuncture samples. Sensitivity of the Aptima assay for HCV RNA quantification from DBS (≥10 IU/mL in plasma) was 100% and specificity was 100%. Sensitivity for HCV RNA detection from DBS was 95.6% and specificity was 94.1%. A small bias in plasma over DBS was observed with good agreement (R2â =â 0.96). CONCLUSIONS: The Aptima HCV Quant assay detects active infection from DBS samples with acceptable diagnostic performance and is clinically comparable to plasma. These data will strengthen the case for the registration of a DBS kit insert claim, enabling future clinical utility.
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Hepacivirus , Hepatitis C , Australia , Pruebas con Sangre Seca , Hepacivirus/aislamiento & purificación , Hepatitis C/diagnóstico , Humanos , Flebotomía , ARN Viral/aislamiento & purificación , Sensibilidad y Especificidad , Carga ViralRESUMEN
BACKGROUND: The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT). METHODS: Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. RESULTS: Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2-2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6-6.3) overall and 17.9/100 person-years (95% CI, 5.8-55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. CONCLUSIONS: These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination. CLINICAL TRIALS REGISTRATION: NCT02336139 and NCT02498015.
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Hepatitis C Crónica , Hepatitis C , Preparaciones Farmacéuticas , Abuso de Sustancias por Vía Intravenosa , Antivirales/uso terapéutico , Femenino , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Reinfección , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológicoRESUMEN
BACKGROUND & AIMS: Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens; however, large randomised studies are lacking. METHODS: REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early. RESULTS: The primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n = 93), standard arm (n = 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4-89.0) in the short arm and 86/95, 90.5% (95% CI 82.7-95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8-95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0-99.7; difference -8.3%, p = 0.025). CONCLUSIONS: In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy. LAY SUMMARY: In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. CLINICALTRIALS. GOV IDENTIFIER: NCT02625909.
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Carbamatos/farmacología , Hepatitis C/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Sofosbuvir/farmacología , Factores de Tiempo , Adulto , Antivirales/farmacología , Antivirales/uso terapéutico , Australia , Canadá , Carbamatos/uso terapéutico , Combinación de Medicamentos , Femenino , Alemania , Hepatitis C/fisiopatología , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Nueva Zelanda , Sofosbuvir/uso terapéutico , Suiza , Resultado del Tratamiento , Reino UnidoRESUMEN
BACKGROUND: HIV self-testing was proved as an effective tool for increasing testing frequency in gay and bisexual men at high risk of infection. Questions remain about understanding why HIVST encouraged testing and how such success can be translated to programmatic implementation. METHODS: We conducted a qualitative investigation of how FORTH participants experienced and perceived HIVST. Stratified sampling was used to recruit gay and bisexual men participating in the FORTH HIVST intervention to take part in interviews, focusing on infrequent testers and those who had received inaccurate HIVST results. RESULTS: Our analysis identified several prominent themes organized into two overarching domains from the 15 interviews: (i) aspects of HIVST contributing to HIV testing frequency, and (ii) sustaining HIVST into the future. Participants also believed that their use of HIVST in the future would depend on the test kit's reliability, particularly when compared with highly reliable clinic-based testing. CONCLUSION: HIVST increases the frequency of HIV testing among gay and bisexual men due, in part, to the practical, psychological, and social benefits it offers. To capitalize fully on these benefits, however, strategies to ensure the availability of highly reliable HIVST are required to sustain benefits beyond the confines of a structured research study.
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Infecciones por VIH , Minorías Sexuales y de Género , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Prueba de VIH , Humanos , Masculino , Reproducibilidad de los Resultados , AutoevaluaciónRESUMEN
The World Health Organization has set a goal to eliminate hepatitis C virus (HCV) infection as public health threat by 2030. Although the advent of highly effective and tolerable direct-acting antiviral therapy has paved the way for HCV elimination, most people with HCV infection remain undiagnosed and untreated globally, with striking disparities between high-income and low- to middle-income countries. Novel decentralized and cost-effective "test-and-treat" strategies are critically needed to identify the millions of people unaware of their status and link them to treatment.
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Antivirales/uso terapéutico , Erradicación de la Enfermedad/organización & administración , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Algoritmos , Hepacivirus/aislamiento & purificación , Humanos , Pruebas en el Punto de Atención , Factores Socioeconómicos , Organización Mundial de la SaludRESUMEN
BACKGROUND: Xpert HCV Viral Load Fingerstick assay (Xpert HCV VL FS) is a point-of-care test quantifying HCV RNA in <1 hour, enabling same-visit diagnosis and treatment. METHODS: This study evaluated time to HCV RNA detection using the Xpert HCV VL FS assay. Fingerstick whole-blood samples were collected from participants in an observational cohort in Australia. RESULTS: In May 2018-2019, 1468 participants were enrolled, 1426 had Xpert HCV VL FS testing performed, and 1386 had a valid result. HCV RNA was detected in 23% (325/1386). Among people with undetectable HCV RNA (nâ =â 1061), median time to result was 57 minutes. Among people with detectable HCV RNA (nâ =â 325), median time to HCV RNA detection was 32 minutes and 80% (261/325) had a detectable HCV RNA result in ≤40 minutes. Median time to HCV RNA detection was dependent on HCV RNA level. CONCLUSIONS: A quicker HCV diagnosis could be achieved by monitoring the time when HCV RNA is first detected with the Xpert HCV VL FS test, rather than HCV RNA quantification, although the current platform does not allow for this. These findings could facilitate new strategies to reduce waiting times for an HCV diagnosis and improve linkage to treatment.
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Hepacivirus/aislamiento & purificación , Hepatitis C/diagnóstico , Pruebas en el Punto de Atención , Juego de Reactivos para Diagnóstico , Carga Viral , Adulto , Recolección de Muestras de Sangre/instrumentación , Estudios de Factibilidad , Femenino , Dedos , Hepacivirus/genética , Hepatitis C/sangre , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , ARN Viral/aislamiento & purificación , Factores de TiempoRESUMEN
The global scale-up of hepatitis C virus (HCV) diagnosis requires simplified and affordable HCV diagnostic pathways. This study evaluated the sensitivity and specificity of the HCV Architect core antigen (HCVcAg) assay for detection of active HCV infection in plasma and capillary whole blood dried blood spots (DBS) compared with HCV RNA testing in plasma (Abbott RealTime HCV Viral Load). Samples were collected from participants in an observational cohort enrolled at three sites in Australia (two-drug treatment and alcohol clinics and one homelessness service). Of 205 participants, 200 had results across all samples and assay types and 186 were included in this analysis (14 participants receiving HCV therapy were excluded). HCV RNA was detected in 29% of participants ([95% CI: 22.6-36.1], 54 of 186). The sensitivity of HCVcAg for detection of active HCV infection in plasma was 98.1% (95% CI: 90-100) and 100% (95% CI: 93-100) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The sensitivity of the HCVcAg assay for detection of active HCV infection in DBS was 90.7% (95% CI: 80-97) and 92.5% (95% CI: 82-98) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The specificity of HCV core antigen for detection of active infection was 100% (95% CI: 97-100) for all samples and RNA thresholds. These data indicate that the detection of HCVcAg is a useful tool for determining active HCV infection; to facilitate enhanced testing, linkage to care and treatment particularly when testing plasma samples are collected by venepuncture.
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Hepacivirus , Antígenos de la Hepatitis C , Hepatitis C/epidemiología , Hepatitis C/virología , Proteínas del Núcleo Viral , Adulto , Estudios de Cohortes , Femenino , Hepacivirus/inmunología , Hepatitis C/inmunología , Antígenos de la Hepatitis C/sangre , Antígenos de la Hepatitis C/inmunología , Humanos , Masculino , Persona de Mediana Edad , Vigilancia en Salud Pública , Sensibilidad y Especificidad , Estudios Seroepidemiológicos , Pruebas Serológicas , Proteínas del Núcleo Viral/sangre , Proteínas del Núcleo Viral/inmunologíaRESUMEN
Point-of-care hepatitis C virus (HCV) RNA testing is advantageous, enabling diagnosis of active infection in a single visit. This study evaluated the sensitivity and specificity of the Xpert HCV Viral Load Finger-Stick assay (Xpert HCV VL FS) for HCV RNA detection (finger-stick) and the Xpert HCV Viral Load assay (plasma) compared with the Abbott RealTime HCV Viral Load assay by venepuncture. Plasma and finger-stick capillary whole-blood samples were collected from participants in an observational cohort in Australia. Of 223 participants enrolled, HCV RNA was detected in 40% of participants (85 of 210) with available Xpert HCV Viral Load testing. Participants receiving HCV therapy were excluded from subsequent analyses (n = 16). Sensitivity of the Xpert HCV Viral Load assay for HCV RNA quantification in plasma collected by venepuncture was 100.0% (95% confidence interval [CI] 96.9%-100.0%) and specificity was 100.0% (95% CI, 94.4%-100.0%). Sensitivity of the Xpert HCV VL FS assay for HCV RNA quantification in samples collected by finger-stick was 100.0% (95% CI, 93.9%-100.0%) and specificity was 100.0% (95% CI, 96.6%-100.0%). The Xpert HCV VL FS test can accurately detect active infection from a finger-stick sample in 1 hour allowing single-visit HCV diagnosis.
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Bioensayo/métodos , Hepacivirus/genética , Hepatitis C/virología , Carga Viral/métodos , Adulto , Australia , Recolección de Muestras de Sangre/métodos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistemas de Atención de Punto , Pruebas en el Punto de Atención , ARN Viral/genética , Sensibilidad y Especificidad , Pruebas Serológicas/métodosRESUMEN
Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as ≥250 IU/mL). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30%) decreased with infection duration (odds ratio [OR] per week of 0.93; 95% CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR = 0.14; 95% CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20%) was estimated at 48% (95% CI:39-56%), 36% (95% CI:20-52%), and 65% (95% CI:54-75%) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (≥52 weeks infection duration, all genotypes) was 96% (95% CI:90-98%). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognized.
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Anticuerpos Antivirales/inmunología , Afinidad de Anticuerpos , Hepacivirus/inmunología , Hepatitis C Crónica/diagnóstico , Hepatitis C/diagnóstico , Enfermedad Aguda/epidemiología , Adulto , Australia/epidemiología , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C/sangre , Hepatitis C/epidemiología , Hepatitis C/inmunología , Hepatitis C Crónica/sangre , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/inmunología , Humanos , Masculino , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
Combining phylogenetic and network methodologies has the potential to better inform targeted interventions to prevent and treat infectious diseases. This study reconstructed a molecular transmission network for people with recent hepatitis C virus (HCV) infection and modelled the impact of targeting directly acting antiviral (DAA) treatment for HCV in the network. Participants were selected from three Australian studies of recent HCV from 2004 to 2014. HCV sequence data (Core-E2) from participants at the time of recent HCV detection were analysed to infer a network by connecting pairs of sequences whose divergence was ≤.03 substitutions/site. Logistic regression was used to identify factors associated with connectivity. Impact of targeting HCV DAAs at both HIV co-infected and random nodes was simulated (1 million replicates). Among 236 participants, 21% (n=49) were connected in the network. HCV/HIV co-infected participants (47%) were more likely to be connected compared to HCV mono-infected participants (16%) (OR 4.56; 95% CI; 2.13-9.74). Simulations targeting DAA HCV treatment to HCV/HIV co-infected individuals prevented 2.5 times more onward infections than providing DAAs to randomly selected individuals. Results demonstrate that genetic distance-based network analyses can be used to identify characteristics associated with HCV transmission, informing targeted prevention and treatment strategies.
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Transmisión de Enfermedad Infecciosa , Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C/transmisión , Adulto , Antivirales/uso terapéutico , Australia/epidemiología , Análisis por Conglomerados , Femenino , Genotipo , Infecciones por VIH/complicaciones , Hepacivirus/aislamiento & purificación , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Filogenia , Análisis de Secuencia de ADN , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The aims of this analysis were to investigate treatment completion and adherence among people with ongoing injecting drug use or receiving opioid substitution therapy (OST) in a study of response-guided therapy for chronic HCV genotypes 2/3 infection. METHODS: ACTIVATE was a multicenter clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b (PEG-IFN) and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Outcomes included treatment completion, PEG-IFN adherence, ribavirin adherence, and sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment). RESULTS: Among 93 people treated, 59% had recently injected drugs (past month), 77% were receiving OST and 56% injected drugs during therapy. Overall, 76% completed treatment. Mean on-treatment adherence to PEG-IFN and ribavirin were 98.2% and 94.6%. Overall, 6% of participants missed >1 dose of PEG-IFN and 31% took <95% of their prescribed ribavirin., Higher treatment completion was observed among those receiving 12 vs. 24 weeks of treatment (97% vs. 46%, P < 0.001) while the proportion of participants with 95% on-treatment ribavirin adherence was similar between groups (67% vs. 72%, P = 0.664). Receiving 12 weeks of therapy was independently associated with treatment completion. No factors were associated with 95% RBV adherence. Neither recent injecting drug use at baseline nor during therapy was associated with treatment completion or adherence to ribavirin. In adjusted analysis, treatment completion was associated with SVR (aOR 23.9, 95% CI 2.9-193.8). CONCLUSIONS: This study demonstrated a high adherence to directly observed PEG-IFN and self-administered ribavirin among people with ongoing injecting drug use or receiving OST. These data also suggest that shortening therapy from 24 to 12 weeks can lead to improved treatment completion. Treatment completion was associated with improved response to therapy. ACTIVATE trial registration number: NCT01364090 - May 31, 2011.
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Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Cooperación del Paciente/estadística & datos numéricos , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/patogenicidad , Hepatitis C/psicología , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Tratamiento de Sustitución de Opiáceos , Proteínas Recombinantes/uso terapéutico , Autoadministración , Resultado del TratamientoRESUMEN
BACKGROUND: This study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis. METHODS: Participants in the ATAHC study, a prospective study of recent HCV infection, with detectable HCV RNA at the time of HCV detection were included. Plasma levels of 27 cytokines and chemokines were measured and their correlation with ALT and HCV RNA levels were assessed. Log10 transformed cytokines and ALT values were used in the analysis. RESULTS: Among 117 individuals, the plasma levels of interferon-gamma inducible protein-10 (IP-10) and macrophage inflammatory protein-1beta (MIP-1ß) were positively correlated with ALT levels (IP-10: r = 0.42, P < 0.001; MIP-1ß: r = 0.29, P = 0.001) and HCV RNA levels (IP-10: rs = 0.44, P < 0.001; MIP-1ß: rs = 0.43, P < 0.001). Using linear regression, after adjusting for sex, age, infection duration, symptomatic infection, HIV co-infection, interferon-lambda rs12979860 genotype, HCV genotype, and assay run, higher ALT levels (ß = 0.20; 95 % CI: 0.07, 0.32; P = 0.002) and HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; ß = 0.16; 95 % CI: 0.03, 0.28; P = 0.014) were independently associated with higher IP-10 levels. HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; ß = 0.16; 95 % CI: 0.01, 0.31; P = 0.036) were associated with higher MIP-1ß levels. CONCLUSIONS: During acute HCV infection, high ALT and HCV RNA levels were associated with increased IP-10 levels, while high HCV RNA levels were also associated with increased MIP-1ß levels. These data suggest that IP-10 and MIP-1ß may have a role in HCV immuno-pathogenesis starting early in acute HCV infection.
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Alanina Transaminasa/sangre , Citocinas/sangre , Hepacivirus/genética , Hepatitis C/sangre , Hepatitis C/virología , Mediadores de Inflamación/sangre , Carga Viral , Enfermedad Aguda , Adulto , Biomarcadores , Quimiocinas/sangre , Coinfección , Femenino , Genotipo , Infecciones por VIH , Hepatitis C/diagnóstico , Humanos , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV) infection leads to more rapid progression of hepatitis C virus (HCV)-related liver fibrosis, which could be linked to differences in the severity of liver inflammation among HIV/HCV co-infected individuals compared to HCV mono-infected individuals. This study assessed the association of HIV co-infection with pro-inflammatory and pro-fibrogenic cytokines and chemokines during recent HCV infection. METHODS: Participants from the ATAHC study, a prospective cohort of recent HCV infection, with detectable HCV RNA at the time of acute HCV detection were included. Concentrations of 27 plasma cytokines and chemokines were measured by multiplex immunoassays and compared between those with, and without, HIV co-infection. RESULTS: Out of 117 individuals with recent HCV infection included in analysis, 73 had HCV mono-infection and 44 had HIV/HCV co-infection. Individuals with HIV/HCV co-infection had significantly higher mean levels of eotaxin (1.79 vs. 1.62 log pg/mL; P < 0.001), monocyte chemotactic protein 1 (MCP-1; 2.10 vs. 1.98 log pg/mL; P < 0.001), and interferon-gamma inducible protein-10 (IP-10; 3.11 vs. 2.98 log pg/mL; P = 0.013). Linear regression analyses adjusting for age, alanine transaminase (ALT), HCV RNA levels, and assay run, higher eotaxin levels were independently associated with HIV/HCV co-infection (adjusted ß: 0.12; 95%CI: 0.01, 0.24; P = 0.039). Higher MCP-1 levels were also independently associated with HIV/HCV co-infection in adjusted analysis (adjusted ß: 0.11; 95%CI: 0.03, 0.18; P = 0.009). CONCLUSIONS: During recent HCV, those with HIV/HCV co-infection had a stronger pro-fibrogenic mediator profile compared to those with HCV mono-infection. These findings may provide a potential explanation for accelerated liver fibrosis in HIV/HCV co-infection. TRIAL REGISTRATION: Australian Trial in Acute Hepatitis C (ATAHC) study was registered with ClinicalTrials.gov registry on September 11, 2005. NCT00192569 .
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Quimiocina CCL11/sangre , Quimiocina CCL2/sangre , Infecciones por VIH/sangre , Hepatitis C/sangre , Adulto , Alanina Transaminasa/sangre , Australia , Coinfección/sangre , Coinfección/virología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1 , Hepacivirus/inmunología , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Interferón gamma/sangre , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: We aimed to characterize seminal hepatitis C virus (HCV) RNA dynamics in human immunodeficiency virus (HIV)-positive men with acute HCV infection given its potential role in sexual transmission of HCV. METHODS: Men with acute HCV infection (duration, ≤12 months) or chronic HCV infection (duration, >12 months) were prospectively recruited. Paired semen and blood samples were assayed for HCV RNA levels. Results were analyzed using χ(2), Fisher exact, Mann-Whitney U, and Kruskal-Wallis tests. RESULTS: Eighteen men (27.3%) had acute HCV and HIV coinfection, 22 (33.3%) had chronic HCV infection and HIV coinfection, and 26 (39.4%) had chronic HCV monoinfection. HCV RNA was detected in semen specimens from 29 of 66 men (43.9%). The median HCV RNA level in blood was 4.0 log IU/mL higher than that in semen. HCV RNA levels were correlated in semen and blood (r(2) = 0.142). Neither HIV positivity nor acute HCV infection was associated with an increased frequency of seminal HCV RNA detection. Among men with acute HCV and HIV coinfection, the median HCV RNA level in blood specimens from those with seminal HCV RNA was higher than that in blood specimens from those without seminal HCV RNA (P = .001). Seminal HCV RNA was detected in ≥1 sample for 26 of 35 men (74.3%) attending follow up. CONCLUSIONS: HCV RNA was detected in semen during both acute and chronic HCV infection. This was unaffected by HIV positivity or the phase of HCV infection. Elevated seminal HCV RNA levels could contribute to sexual transmission of HCV, but other factors, including high-risk behaviors, may be the main drivers for HCV transmission in HIV-infected individuals.
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Hepacivirus/aislamiento & purificación , Semen/virología , Carga Viral , Adulto , Sangre/virología , Estudios de Cohortes , Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral/aislamiento & purificaciónRESUMEN
Background: Simplified hepatitis C virus (HCV) testing integrated into existing HIV services has the potential to improve HCV diagnoses and treatment. We evaluated the cost-effectiveness of integrating different simplified HCV testing strategies into existing HIV pre-exposure prophylaxis (PrEP) and treatment services among men who have sex with men (MSM) in Taiwan. Methods: Mathematical modeling was used to assess the cost-effectiveness of integrating simplified HCV tests (point-of-care antibody, reflex RNA, or immediate point-of-care RNA) with HCV treatment into existing HIV prevention and care for MSM from a healthcare perspective. The impact of increasing PrEP and HIV treatment coverage among MSM in combination with these HCV testing strategies was also considered. We reported lifetime costs (2022 US dollars) and quality-adjusted life years (QALYs) and calculated incremental cost-effectiveness ratios (ICERs) with a 3% annual discounting rate. Findings: Point-of-care HCV antibody and reflex RNA testing are cost-effective compared to current HCV testing in all PrEP and HIV treatment coverage scenarios (ICERs <$32,811/QALY gained). Immediate point-of-care RNA testing would be only cost-effective compared to the current HCV testing if coverage of HIV services remained unchanged. Point-of-care antibody testing in an unchanged HIV services coverage scenario and all simplified HCV testing strategies in scenarios that increased both HIV PrEP and treatment coverage form an efficient frontier, indicating best value for money strategies. Interpretation: Our findings support the integration of simplified HCV testing and people-centered services for MSM and highlight the economic benefits of integrating simplified HCV testing into existing services for MSM alongside HIV PrEP and treatment. Funding: This study was made possible as part of a research-funded PhD being undertaken by HJW under the UNSW Sydney Scientia scholarship and was associated with the Rapid Point of Care Research Consortium for infectious disease in the Asia Pacific (RAPID), which is funded by an NHMRC Centre for Research Excellence. JG is supported by a National Health and Medical Research Council Investigator Grant (1176131).
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INTRODUCTION: Simplified hepatitis C virus (HCV) diagnostic strategies have the potential to improve HCV diagnoses and treatment. We aimed to investigate the impact of simplified HCV diagnostic strategies on HCV incidence and its effect on HCV diagnosis and treatment among men who have sex with men (MSM) regardless of HIV status and use of HIV pre-exposure prophylaxis (PrEP) in Taiwan. METHODS: A compartmental deterministic model was developed to describe the natural history of HCV disease progression, the HCV care cascade and the HIV status and PrEP using among MSM. The model was calibrated to available data for HCV and HIV epidemiology and population demographics in Taiwan. We simulated the epidemic from 2004 and projected the impact of simplified testing strategies on the HCV epidemic among MSM over 2022-2030. RESULTS: Under the current testing approach in Taiwan, total HCV incidence would increase to 12.6 per 1000 person-years among MSM by 2030. Single-visit point-of-care RNA testing had the largest impact on reducing the number of new HCV infections over 2022-2030, with a 31.1% reduction (interquartile range: 24.9%-32.8%). By 2030, single-visit point-of-care HCV testing improved HCV diagnosis to 90.9%, HCV treatment to 87.7% and HCV cure to 81.5% among MSM living with HCV. Compared to status quo, prioritized simplified HCV testing for PrEP users and MSM living with diagnosed HIV had considerable impact on the broader HCV epidemic among MSM. A sensitivity analysis suggests that reinfection risk would have a large impact on the effectiveness of each point-of-care testing scenario. CONCLUSIONS: Simplified HCV diagnostic strategies could control the ongoing HCV epidemic and improve HCV testing and treatment among Taiwanese MSM. Single-visit point-of-care RNA testing would result in large reductions in HCV incidence and prevalence among MSM. Efficient risk-reduction strategies will need to be implemented alongside point-of-care testing to achieve HCV elimination among MSM in Taiwan.
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Infecciones por VIH , Hepatitis C , Homosexualidad Masculina , Profilaxis Pre-Exposición , Humanos , Masculino , Taiwán/epidemiología , Homosexualidad Masculina/estadística & datos numéricos , Profilaxis Pre-Exposición/métodos , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Hepatitis C/prevención & control , Incidencia , Adulto , Epidemias/prevención & control , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION: Progress toward hepatitis C virus (HCV) elimination is impeded by low testing and treatment due to the current diagnostic pathway requiring multiple visits leading to loss to follow-up. Point-of-care testing technologies capable of detecting current HCV infection in one hour are a 'game-changer.' These tests enable diagnosis and treatment in a single visit, overcoming the barrier of multiple visits that frequently leads to loss to follow-up. Combining point-of-care HCV antibody and RNA tests should improve cost-effectiveness, patient/provider acceptability, and testing efficiency. However, implementing HCV point-of-care testing programs at scale requires multiple considerations. AREAS COVERED: This commentary explores the need for point-of-care HCV tests, diagnostic strategies to improve HCV testing, key considerations for implementing point-of-care HCV testing programs, and remaining challenges for point-of-care testing (including operator training, quality management, connectivity and reporting systems, regulatory approval processes, and the need for more efficient tests). EXPERT OPINION: It is exciting that single-visit testing, diagnosis, and treatment for HCV infection have been achieved. Innovations afforded through COVID-19 should facilitate the accelerated development of low-cost, rapid, and accurate tests to improve HCV testing. The next challenge will be to address barriers and facilitators for implementing point-of-care testing to deliver them at scale.
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Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Humanos , Hepatitis C/diagnóstico , Hepatitis C/terapia , Hepacivirus/genética , Pruebas en el Punto de Atención , ARN ViralRESUMEN
BACKGROUND: Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial. METHODS: For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population. FINDINGS: The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6-43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed. INTERPRETATION: Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM. FUNDING: National Institutes of Health and Dr. C.J. Vaillant Fonds.