Screening for Hepatitis C Virus Reinfection Using a Behaviour-Based Risk Score among Men Who Have Sex with Men with HIV:Results from a Case–Control Diagnostic Validation Study

We assessed the predictive capacity of the HCV-MOSAIC risk score, originally developed for primary early HCV infection, as a screening tool for HCV reinfection in 103 men who have sex with men (MSM) with HIV using data from the MOSAIC cohort, including MSM with HIV/HCV-coinfection who became reinfected (cases, n = 27) or not (controls, n = 76) during follow-up. The overall predictive capacity of the score was assessed using the area under the receiver operating characteristic (AUROC) curve. The effects of covariates on the receiver operating characteristic (ROC) curve were assessed using parametric ROC regression. The score cut-off validated for primary early infection (≥2.0) was used, from which the sensitivity and specificity were calculated. The AUROC was 0.74 (95% confidence interval (CI) = 0.63–0.84). Group sex significantly increased the predictive capacity. Using the validated cut-off, sensitivity was 70.4% (95%CI = 49.8–86.2%) and specificity was 59.2% (95%CI: 47.3–70.4%). External validation from a cohort of 25 cases and 111 controls, all MSM with HIV, resulted in a sensitivity of 44.0% (95%CI = 24.4–65.1) and specificity of 71.2% (95%CI = 61.8–79.4). The HCV-MOSAIC risk score may be useful for identifying individuals at risk of HCV reinfection. In sexual health or HIV-care settings, this score could help guide HCV-RNA testing in MSM with a prior HCV infection.</p

Spontaneous Clearance of Hepatitis C Virus Infection Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men

We assessed spontaneous clearance in 27 human immunodeficiency virus-infected men who have sex with men (MSM) who seroconverted for hepatitis C virus (HCV). In contrast with a recent estimate of 45.8%, we found a spontaneous clearance rate of 11.1% (95% confidence interval = 2.4-29.2). This finding suggests that treatment deferral to await spontaneous clearance might not be justified for MSM with sexually acquired HC

Limitations and Opportunities of Transcutaneous Bilirubin Measurements

OBJECTIVE: Although transcutaneous bilirubinometers have existed for over 30 years, the clinical utility of the technique is limited to a screening method for hyperbilirubinemia, rather than a replacement for invasive blood sampling. In this study, we investigate the reason for this limited clinical value and address possibilities for improvement. METHODS: To obtain better insight into the physiology of bilirubin measurements, we evaluated a transcutaneous bilirubinometer that determines not only the cutaneous bilirubin concentration (TcB) but also the blood volume fraction (BVF) in the investigated skin volume. For 49 neonates (gestational age 30 +/- 3.1 weeks, postnatal age 6 [4-10] days) at our NICU, we performed 124 TcB and 55 BVF measurements. RESULTS: The TcB correlated well with the total serum bilirubin concentration (TSB) (r = 0.88) with an uncertainty of 55 mu mol/L. The BVF in the measured skin volume ranged between 0.1% and 0.75%. CONCLUSIONS: The performance of our bilirubinometer is comparable to existing transcutaneous devices. The limited clinical value of current bilirubinometers can be explained by the low BVF in the skin volume that is probed by these devices. Because the TcB depends for over 99% on the contribution of extravascular bilirubin, it is a physiologically different parameter from the TSB. Hence, the standard method of evaluation that compares the TcB to the TSB is insufficient to fully investigate the clinical value of transcutaneous bilirubinometers, ie, their predictive value for kernicterus. We suggest that the clinical value may be improved considerably by changing either the method of evaluation or the technological design of transcutaneous bilirubinometers. Pediatrics 2012;129:689-69

Development and validation of the HCV-MOSAIC risk score to assist testing for acute hepatitis C virus (HCV) infection in HIV-infected men who have sex with men (MSM)

Current guidelines recommend hepatitis C virus (HCV) testing for HIV-infected men who have sex with men (MSM) with ongoing risk behaviour, without specifying the type of risk behaviour. We developed and validated the HCV-MOSAIC risk score to assist HCV testing in HIV-infected MSM. The risk score consisted of six self-reported risk factors identified using multivariable logistic regression using data from the Dutch MOSAIC study (n = 213, 2009-2013). Area under the ROC curve (AUC), sensitivity, specificity, post-test-probability-of-disease and diagnostic gain were calculated. The risk score was validated in case-control studies from Belgium (n = 142, 2010-2013) and the United Kingdom (n = 190, 2003-2005) and in cross-sectional surveys at a Dutch sexually transmitted infections clinic (n = 284, 2007-2009). The AUC was 0.82; sensitivity 78.0% and specificity 78.6%. In the validation studies sensitivity ranged from 73.1% to 100% and specificity from 56.2% to 65.6%. The post-test-probability-of-disease ranged from 5.9% to 20.0% given acute HCV prevalence of 1.7% to 6.4%, yielding a diagnostic gain of 4.2% to 13.6%. The HCV-MOSAIC risk score can successfully identify HIV-infected MSM at risk for acute HCV infection. It could be a promising tool to improve HCV testing strategies in various setting

Progression of liver fibrosis following acute hepatitis C virus infection in HIV-positive MSM

BACKGROUND: Whether continued, accelerated liver fibrosis progression occurs following acute hepatitis C virus infection (AHCVI) in HIV-positive MSM is unknown. DESIGN AND METHODS: HIV-positive MSM from the AIDS Therapy Evaluation in the Netherlands and MSM Observational Study for Acute Infection with Hepatitis C-cohorts with primary AHCVI and at least one fibrosis-4 (FIB-4) measurement less than 2 years before and 1 year after estimated AHCVI were included. Mixed-effect linear models were used to evaluate (time-updated) determinants of FIB-4 levels over time. Determinants of transitioning to and from FIB-4 ≤ 1.45 and > 1.45 were examined using multistate Markov models. RESULTS: Of 313 MSM, median FIB-4 measurements per individual was 12 (interquartile range  = 8-18) and median follow-up following AHCVI was 3.5 years (interquartile range = 1.9-5.6). FIB-4 measurements averaged at 1.00 [95% confidence interval (CI) = 0.95-1.05] before AHCVI, 1.31 (95% CI = 1.25-1.38) during the first year of AHCVI and 1.10 (95% CI = 1.05-1.15) more than 1 year after AHCVI. Mean FIB-4 more than 1 year after AHCVI was higher for chronically infected patients compared with those successfully treated (P = 0.007). Overall FIB-4 scores were significantly higher with older age, lower CD4 cell count, longer duration from HIV-diagnosis or AHCVI, and nonresponse to HCV-treatment. At the end of follow-up, 60 (19.2%) and eight MSM (2.6%) had FIB-4 between 1.45-3.25 and ≥ 3.25, respectively. Older age, lower CD4 cell count and detectable HIV-RNA were significantly associated with higher rates of progression to FIB-4 > 1.45, whereas older age, longer duration from HIV-diagnosis and nonresponse to HCV-treatment were significantly associated with lower rates of regression to FIB-4 ≤ 1.45. CONCLUSION: In this population of HIV-positive MSM, FIB-4 scores were higher during the first year of AHCVI, but FIB-4 ≥ 3.25 was uncommon by the end of follow-up. Well controlled HIV-infection appears to attenuate FIB-4 progression

High treatment uptake in human immunodeficiency virus/ hepatitis C virus-coinfected patients after unrestricted access to direct-acting antivirals in the Netherlands

\u3cp\u3eThe Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Methods. Data were obtained from the ATHENA HIV observational cohort in which &gt;98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results. Of 23 574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa-based regimen had failed in 54. Conclusions. Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients.\u3c/p\u3

High Treatment Uptake in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients After Unrestricted Access to Direct-Acting Antivirals in the Netherlands

Background: The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Methods: Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results: Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa-based regimen had failed in 54. Conclusions: Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients

Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection

Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without HIV coinfection. Material and methods: HCV NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for RAVs. RAVs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients. Results: 148 samples were available (n = 68 HIV and n = 80 non-HIV). Relative frequency of clade I and clade II was significantly different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall, HIV infected patients exhibited significantly lower prevalence of RAVs than HIV-uninfected patients (62% vs. 79%, p = 0.03). However, Q80K prevalence was significantly higher in HIV-infected subjects (50% vs. 24%, p = 0.001), whereas prevalence of S122D/G/N/S (2% vs. 16%, p = 0.002) and N174G/N/S (10% vs. 55%, p <0.0001) polymorphisms were significantly lower. Q80K was found exclusively in clade I viruses. S122 (3% vs. 22%, p=0.001) and N174 (13% vs. 75%, p <0.0001) polymorphisms had significantly lower prevalence in clade I than clade II viruses. Conclusions: In the Netherlands, prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. Prevalence of N174 and S122 polymorphisms was significantly higher in clade II than clade I viruse

The hepatitis C virus nonstructural protein 3 Q80K polymorphism is frequently detected and transmitted among HIV-infected MSM in the Netherlands

Objectives: The Q80K polymorphism is a naturally occurring resistance-associated variant in the hepatitis C virus (HCV) nonstructural protein 3 (NS3) region and is likely transmissible between hosts. This study describes the Q80K origin and prevalence among HCV risk groups in the Netherlands and examines whether Q80K is linked to specific transmission networks. Design and methods: Stored blood samples from HCV genotype 1a-infected patients were used for PCR and sequencing to reconstruct the NS3 maximum likelihood phylogeny. The most recent common ancestor was estimated with a coalescent-based model within a Bayesian statistical framework. Results: Study participants (n150)were eitherMSM(39%), peoplewho inject drugs (17%), or patients with other (15%) or unknown/unreported (29%) risk behavior. Overall 45% was coinfected with HIV.Q80Kwaspresent in36%(95%confidence interval 28-44%)of patients throughout the sample collection period (2000-2015) and wasmost prevalent inMSM(52%, 95%confidenceinterval38-65%). FiveMSM-specific transmission clusterswereidentified,of which three exclusively contained sequences with Q80K. The HCV-1a most recent common ancestor in the Netherlands was estimated in 1914 (95% higher posterior density 1879-1944) andQ80Koriginated in1957(95%higher posterior density1942-1970) withinHCV-1aclade I. All Q80K lineages could be traced back to this single origin. Conclusion: Q80K is a highly stable and transmissible resistance-associated variant and was present in a large part of Dutch HIV-coinfected MSM. The introduction and expansion of Q80K variants in this key population suggest a founder effect, potentially jeopardizing future treatment with simeprevir