scholarly journals A22 Phylogenetic clustering of hepatitis C virus infection among people who inject drugs in Baltimore

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Oluwaseun Falade-Nwulia ◽  
Jada Hackman ◽  
Shruti Mehta ◽  
Mark Sulkowski ◽  
Carl Latkin ◽  
...  

Abstract The availability of effective, oral direct acting antivirals for hepatitis C virus (HCV) treatment has fueled optimism for HCV elimination through treatment as prevention (TasP) among people who inject drugs (PWID). Identifying characteristics of individuals in transmission networks would provide critical information for the development and implementation of effective, targeted HCV TasP strategies. The AIDS linked to the IntraVenous Experience (ALIVE) cohort has followed PWID in Baltimore since 1988. Sequencing of the HCV core/E1 region (342 nucleotides) was performed on HCV viremic samples from the most recent study visit attended by ALIVE participants between August, 2005 and December, 2016. Outgroup sequences were retrieved from GenBank through a BLAST search for HCV sequences similar to study sequences to support identification of ‘local clusters’ and were aligned to study sequences using Clustal O. Phylogenetic trees were inferred for each of HCV subtype 1a and 1b separately through maximum likelihood analysis implemented in the MEGA X software using the Tamura-Nei model with gamma distribution and invariant sites. Nucleotide substitution model selection was based on the corrected Akaike information criterion scores of various models in MEGA. Robustness of the resulting tree was assessed by bootstrapping with 1,000 replicates. Clusters were identified using ClusterPicker software (70% bootstrap threshold and 0.05 maximum genetic distance threshold). Sensitivity analyses were performed by varying the genetic distance threshold between 0.025 and 0.05 to determine the effect on identification of factors associated with clustering. HCV infection clustering was defined as > 2 participants with HCV genome sequences satisfying 70 per cent bootstrap and 0.05 genetic threshold distance requirement for sequence similarity. Logistic regression was used to assess sociodemographic factors associated with being in an HCV cluster. Among 512 HCV genotype 1 viremic PWID, HCV subtype prevalence was 83 per cent genotype 1a and 17 per cent genotype 1b. The median age of participants was 54 years, 68 per cent male, 87 per cent Black, and 38 per cent HIV infected. Overall, 9 per cent (n = 44) were grouped into 21 clusters, consisting of 20 pairs and 1 triad. Of the 425 genotype 1a and 87 genotype 1b samples evaluated, 8 per cent (n = 33) and 13 per cent (n = 11) respectively, were in clusters. In unadjusted analyses, membership in a cluster, was associated with younger age (odds ratio (OR) 1.5 [95% confidence interval (CI) 1.1–2.1] per 10 year age decrease); female sex (OR 2.8 [95% CI 1.5–5.3]), HIV infection (OR 4.9 [95% CI 2.5–9.9]), and living in East Baltimore (versus outside East Baltimore, OR 2.0 [95% CI 1.0–3.9]). In adjusted analyses, female sex (OR 2.0 [95% CI 1.0–3.9] and HIV infection (OR 5.4 [95% CI 2.6–11.1] remained independently associated with being in an HCV infection cluster. HIV-infected PWID and their networks should be prioritized for HCV treatment and prevention interventions given an increased likelihood of transmission in these groups.

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249585
Author(s):  
Ali Mirzazadeh ◽  
Yea-Hung Chen ◽  
Jess Lin ◽  
Katie Burk ◽  
Erin C. Wilson ◽  
...  

Background People who inject drugs (PWID) are disproportionately affected by hepatitis C virus (HCV). Data tracking the engagement of PWID in the continuum of HCV care are needed to assess the reach, target the response, and gauge impact of HCV elimination efforts. Methods We analyzed data from the National HIV Behavioral Surveillance (NHBS) surveys of PWID recruited via respondent driven sampling (RDS) in San Francisco in 2018. We calculated the number and proportion who self-reported ever: (1) tested for HCV, (2) tested positive for HCV antibody, (3) diagnosed with HCV, (4) received HCV treatment, (5) and attained sustained viral response (SVR). To assess temporal changes, we compared 2018 estimates to those from the 2015 NHBS sample. Results Of 456 PWID interviewed in 2018, 88% had previously been tested for HCV, 63% tested antibody positive, and 50% were diagnosed with HCV infection. Of those diagnosed, 42% received treatment. Eighty-one percent of those who received treatment attained SVR. In 2015 a similar proportion of PWID were tested and received an HCV diagnosis, compared to 2018. However, HCV treatment was more prevalent in the 2018 sample (19% vs. 42%, P-value 0.01). Adjusted analysis of 2018 survey data showed having no health insurance (APR 1.6, P-value 0.01) and having no usual source of health care (APR 1.5, P-value 0.01) were significantly associated with untreated HCV prevalence. Conclusion While findings indicate an improvement in HCV treatment uptake among PWID in San Francisco, more than half of PWID diagnosed with HCV infection had not received HCV treatment in 2018. Policies and interventions to increase coverage are necessary, particularly among PWID who are uninsured and outside of regular care.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Oluwaseun Falade-Nwulia ◽  
Jada Hackman ◽  
Shruti H. Mehta ◽  
Sean D. McCormick ◽  
Gregory D. Kirk ◽  
...  

Abstract Background The availability of effective, oral direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has put elimination of HCV as a public health challenge within reach. However, little is known about the characteristics of transmission networks of people who inject drugs (PWID). Methods Sequencing of a segment of the HCV genome was performed on samples collected from a community-based cohort of PWID between August 2005 and December 2016. Phylogenetic trees were inferred, and clusters were identified (70% bootstrap threshold; 0.04 maximum genetic distance threshold). We describe sex, race, age difference, and HIV infection status of potential transmission partners. Logistic regression was used to assess factors associated with being in an HCV cluster. Results Of 508 HCV genotype 1 viremic PWID, 8% (n = 41) were grouped into 20 clusters, consisting of 19 pairs and 1 triad. In adjusted analyses, female sex (odds ratio [OR] 2.3 [95% confidence interval (CI) 1.2–4.5]) and HIV infection (OR 5.7 [CI 2.7–11.9]) remained independently associated with being in an HCV infection cluster. Conclusions Molecular epidemiological analysis reveals that, in this cohort of PWID in Baltimore, HIV infection and female sex were associated with HCV clustering. Combination HCV prevention interventions targeting HIV infected PWID and addressing HCV infection prevention needs of women have potential to advance HCV elimination efforts.


Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 685
Author(s):  
Emmanuelle V. LeBlanc ◽  
Youjin Kim ◽  
Chantelle J. Capicciotti ◽  
Che C. Colpitts

Chronic hepatitis C virus (HCV) infections continue to be a major contributor to liver disease worldwide. HCV treatment has become highly effective, yet there are still no vaccines or prophylactic strategies available to prevent infection and allow effective management of the global HCV burden. Glycan-dependent interactions are crucial to many aspects of the highly complex HCV entry process, and also modulate immune evasion. This review provides an overview of the roles of viral and cellular glycans in HCV infection and highlights glycan-focused advances in the development of entry inhibitors and vaccines to effectively prevent HCV infection.


2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Carissa E. Chu ◽  
Feng Wu ◽  
Xi He ◽  
Kali Zhou ◽  
Yu Cheng ◽  
...  

Abstract Background.  Hepatitis C virus (HCV) treatment access among human immunodeficiency virus (HIV)/HCV-coinfected people who inject drugs is poor, despite a high burden of disease in this population. Understanding barriers and facilitators to HCV treatment uptake is critical to the implementation of new direct-acting antivirals. Methods.  We conducted in-depth interviews with patients, physicians, and social workers at an HIV treatment facility and methadone maintenance treatment centers in Guangzhou, China to identify barriers and facilitators to HCV treatment. We included patients who were in various stages of HCV treatment and those who were not treated. We used standard qualitative methods and organized data into themes. Results.  Interview data from 29 patients, 8 physicians, and 3 social workers were analyzed. Facilitators and barriers were organized according to a modified Consolidated Framework for Implementation Research schematic. Facilitators included patient trust in physicians, hope for a cure, peer networks, and social support. Barriers included ongoing drug use, low HCV disease knowledge, fragmented reimbursement systems, HIV exceptionalism, and stigma. Conclusions.  Expanding existing harm reduction programs, HIV treatment programs, and social services may facilitate scale-up of direct-acting antivirals globally. Improving integration of ancillary social and mental health services within existing HIV care systems may facilitate HCV treatment access.


Addiction ◽  
2017 ◽  
Vol 112 (7) ◽  
pp. 1302-1314 ◽  
Author(s):  
Jack Stone ◽  
Natasha K. Martin ◽  
Matthew Hickman ◽  
Sharon J. Hutchinson ◽  
Esther Aspinall ◽  
...  

2005 ◽  
Vol 23 (3) ◽  
pp. 468-473 ◽  
Author(s):  
Daniele Vallisa ◽  
Patrizia Bernuzzi ◽  
Luca Arcaini ◽  
Stefano Sacchi ◽  
Vittorio Callea ◽  
...  

Purpose Hepatitis C virus (HCV) is endemic in some areas of Northwestern Europe and the United States. HCV has been shown to play a role in the development of both hepatocellular carcinoma and B-cell non-Hodgkin's lymphoma (B-NHL). The biologic mechanisms underlying the lymphomagenic activity of the virus so far are under investigation. In this study, the role of antiviral (anti-HCV) treatment in B-NHL associated with HCV infection is evaluated. Patients and Methods Thirteen patients with histologically proven low-grade B-NHL characterized by an indolent course (ie, doubling time no less than 1 year, no bulky disease) and carrying HCV infection were enrolled on the study. All patients underwent antiviral treatment alone with pegilated interferon and ribavirin. Response assessment took place at 6 and 12 months. Results Of the twelve assessable patients, seven (58%) achieved complete response and two (16%) partial hematologic response at 14.1 ± 9.7 months (range, 2 to 24 months, median follow-up, 14 months), while two had stable disease with only one patient experiencing progression of disease. Hematologic responses (complete and partial, 75%) were highly significantly associated to clearance or decrease in serum HCV viral load following treatment (P = .005). Virologic response was more likely to be seen in HCV genotype 2 (P = .035), while hematologic response did not correlate with the viral genotype. Treatment-related toxicity did not cause discontinuation of therapy in all but two patients, one of whom, however, achieved complete response. Conclusion This experience strongly provides a role for antiviral treatment in patients affected by HCV-related, low-grade, B-cell NHL.


2004 ◽  
Vol 46 (6) ◽  
pp. 303-308 ◽  
Author(s):  
Ingridt Hildegard Vogler ◽  
Anna Nishiya ◽  
Helena Kaminami Morimoto ◽  
Edna Maria Vissoci Reiche ◽  
André Luiz Bortoliero ◽  
...  

Serological, epidemiological and molecular aspects of hepatitis C virus (HCV) infection were evaluated in 183 subjects from Londrina, Paraná, Brazil, and adjacent areas. Serum samples which tested anti-HCV positive by microparticle enzyme immunoassay (MEIA) obtained from eight patients with chronic hepatitis C, 48 blood donors, and 127 patients infected with the human immunodeficiency virus (HIV) were submitted to another enzyme immunoassay (ELISA) and to the polymerase chain reaction (PCR). About 78.7% of samples were also reactive by ELISA, with the greater proportion (70.8%) of discordant results verified among blood donors. A similar finding was observed for HCV-RNA detection by PCR, with 111/165 (67.3%) positive samples, with higher rates among HIV-positive subjects and patients with chronic hepatitis than among blood donors. Sixty-one PCR-positive samples were submitted to HCV genotyping, with 77.1, 21.3 and 1.6% of the samples identified as types 1, 3 and 2, respectively. Finally, analysis of some risk factors associated with HCV infection showed that intravenous drug use was the most common risk factor among HIV/HCV co-infected patients, while blood transfusion was the most important risk factor in the group without HIV infection. The present study contributed to the knowledge regarding risk factors associated with HCV infection and the distribution of HCV genotypes in the population evaluated.


2015 ◽  
Vol 3 (2) ◽  
pp. 245-249
Author(s):  
Howayda E. Gomaa ◽  
Mohamed Mahmoud ◽  
Nevine E. Saad ◽  
Amal S. Saad-Hussein ◽  
Somaia Ismail ◽  
...  

AIM: We examined the role that immunoglobulin GM 23 and KM allotypes—genetic markers of γ and κ chains, respectively—play in response to treatment of hepatitis C virus (HCV) infection in Egyptian patients.MATERIAL AND METHODS: A total of 120 persons who had responded to HCV treatment and 125 with persistent HCV infection were genotyped for the presence of GM23 and KM determinants. HLA –C genotyping was also done.RESULTS: Association of GM 23+ and KM3 was significantly associated with non response to treatment (P < 0.0001). Individuals who lacked this GM genotype (but were positive for KM1,2 and 3) were likely to respond to treatment (P=0.045). Association of heterozygous GM23 (+/-) with KM 1,2 and 3 or KM3 alone was significantly associated with SVR (P = 0.001) and (P = 0.0001) respectively. Particular combinations of HLA and GM genotypes were associated significantly with the response to HCV treatment. The combination of HLAC2C2 and GM23+ was associated with persistence of infection (P = 0.027) while the association of HLAC2C2 and heterozygous GM23+/- was associated with SVR (P = 0.001).The association of HLAC1C1 and heterozygous GM23+/- was significantly associated with SVR (P = 0.001) and also subjects with HLA C1/C2 and heterozygous GM23+/- were likely to respond to treatment (P = 0.003) while subjects with HLA C1/C2 and GM23+ show tendency to resist to treatment (P = 0.0001).CONCLUSION: Our results didn’t support a role for KM allotypes, GM23 allotype plays a role in the persistence of HCV infection in the presence or absence of KM1,3. Interaction between certain GM and HLA-C genotypes may favor adequate response to interferon based therapies.


2020 ◽  
Author(s):  
Robert Onchong'a Mainga ◽  
Odari Okoth Eddy ◽  
Borus Kimutai Peter ◽  
Ole Kwallah Allan ◽  
Murith Gikunda James ◽  
...  

Abstract Background: Hepatitis C virus is a major global health problem estimated to infect over 170 million people globally with the most common route of infection being injecting drug use (IDU). Treatment for HCV infection has traditionally been shown to be genotype specific; however the available drugs are still expensive and out of reach in many developing countries. To improve on monitoring, there is need to continuously document the genotypic burden and epidemiology in different populations arises. Objectives: This study aimed to determine the circulating genotypes and link the data to the socio-demographics of injecting drug users in Kilifi County along the Kenyan coastline. Methods: Using a random sampling method, this was a cross-sectional prospective study conducted among 127 injecting drug users, whereby ethical clearance was sought from Kenyatta National Hospital/ University of Nairobi Ethical and Research review committee (KNH/UON-ERC), and Reference number P366/07/2017 on 25 th September 2017. Serology for HCV was done followed by nucleic acid amplification and eventual genotyping. Socio-demographic data was collected using questionnaire administered at the sites. Results: A total of 28 (23 males and 5 females) samples out of 127 samples were positive for HCV giving a prevalence of 22.1%. The modal age group was 25- 49 years. Of the positive samples, 11 were amplified by PCR, all from the male IDUs. Prevalent genotypes included genotype 1a (13%) and genotype 4a (87%). Both genotype 1a and 4a were only found in males. Conclusion: Although it is the first time to report HCV4a in Kilifi town and Mtwapa as compared to Watamu and Malindi which had both HCV1a and HCV4a. Tourists born in countries where HCV prevalence is high are supposed to be screened before accessing entry to Kilifi County. No clinical trial was conducted. The study reveals the burden of HCV infection among IDUs in Kilifi County. The Government should formulate policies for intervention on testing and treatment of HCV in Kilifi County targeting IDUs in order to minimize spread to other populations.


Author(s):  
Stella Protopapas ◽  
Liza Bronner Murrison ◽  
Scott L Wexelblatt ◽  
Jason T Blackard ◽  
Eric S Hall

Abstract Purpose This study aims to estimate the disease burden of vertically-acquired hepatitis C virus (HCV) in a large Midwestern hospital; and to identify factors associated with HCV diagnostic testing among high-risk infants. Methods Retrospective analysis of an infant cohort (n=58,427) born from 2014-2016 in the Greater Cincinnati region, where universal maternal urine testing is conducted at delivery to assess for intrauterine drug exposure (IUDE). Demographics and birth characteristics were analyzed among high-risk infants to identify factors associated with receiving HCV testing. A nested matched case-control analysis examined the association of pediatric HCV infection and IUDE. Results The HCV prevalence rate among high-risk infants who received testing was 3.6-5.2% of births. Approximately 66.7% of maternally-acquired HCV infections may be missed using current testing recommendations. Prenatal care had no significant effect (aOR 1.2 [95%CI 0.4-3.5]) on the odds of a high-risk infant receiving HCV testing. Opioid-exposed cases had an over 6-fold increase in the odds of HCV infection (aOR 6.2 [95%CI 2.3-16.6]) compared to non-opioid exposed infants. Conclusions IUDE was significantly associated with increased odds of pediatric HCV infection in this population. The gaps in pediatric HCV testing identified in this study, despite known risk level and maternal infection, suggest the need for increased focus on HCV identification in the pediatric population.


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