Spatiotemporal Phylodynamics of Hepatitis C Among People Who Inject Drugs in India.

BACKGROUND AND AIMS: Implementing effective interventions for HCV requires a detailed understanding of local transmission dynamics and geospatial spread. Little is known about HCV phylodynamics, particularly among high-burden populations, such as people who inject drugs (PWID). APPROACH AND RESULTS: We used 483 HCV sequences and detailed individual-level data from PWID across four Indian cities. Bayesian phylogeographic analyses were used to evaluate transmission hotspots and geospatial diffusion of the virus. Phylogenetic cluster analysis was performed to infer epidemiologic links and factors associated with clustering. A total of 492 HIV sequences were used to draw comparisons within the same population and, in the case of coinfections, evaluate molecular evidence for shared transmission pathways. Overall, 139/483 (28.8%) of HCV sequences clustered with a median cluster size of 3 individuals. Genetically linked participants with HCV were significantly younger and more likely to be infected with HCV subtype 3b as well as to live and inject close to one another. Phylogenetic evidence suggests likely ongoing HCV infection/reinfection with limited support for shared HIV/HCV transmission pathways. Phylogeographic analyses trace historic HCV spread back to Northeastern India and show diffusion patterns consistent with drug trafficking routes. CONCLUSIONS: This study characterizes HCV phylodynamics among PWID in a low and middle-income country setting. Heterogeneity and recent genetic linkage of HCV across geographically disparate Indian states suggest that targeted interventions could help prevent reimportation of virus through drug trafficking routes.

Values and preferences for hepatitis C self-testing among people who inject drugs in Kyrgyzstan.

BACKGROUND: The prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) continues to be a major public-health burden in this highly stigmatised population. To halt transmission of HCV, rapid HCV self-testing kits represent an innovative approach that could enable PWID to know their HCV status and seek treatment. As no HCV test has yet been licenced for self-administration, it is crucial to obtain knowledge around the factors that may deter or foster delivery of HCV self-testing among PWID in resource-constrained countries. METHODS: A qualitative study to assess values and preferences relating to HCV self-testing was conducted in mid-2020 among PWID in the Bishkek and Chui regions of Kyrgyzstan. Forty-seven PWID participated in 15 individual interviews, two group interviews (n = 12) and one participatory action-research session (n = 20). Responses were analysed using a thematic analysis approach with 4 predefined themes: awareness of HCV and current HCV testing experiences, and acceptability and service delivery preferences for HCV self-testing. Informants' insights were analysed using a thematic analysis approach. This research received local ethics approval. RESULTS: Awareness of HCV is low and currently PWID prefer community-based HCV testing due to stigma encountered in other healthcare settings. HCV self-testing would be accepted and appreciated by PWID. Acceptability may increase if HCV self-testing: was delivered in pharmacies or by harm reduction associations; was free of charge; was oral rather than blood-based; included instructions with images and clear information on the test's accuracy; and was distributed alongside pre- and post-testing counselling with linkage to confirmatory testing support. CONCLUSIONS: HCV self-testing could increase awareness of and more frequent testing for HCV infection among PWID in Kyrgyzstan. It is recommended that peer-driven associations are involved in the delivery of any HCV self-testing. Furthermore, efforts should be maximised to end discrimination against PWID at the healthcare institutions responsible for confirmatory HCV testing and treatment provision.

Improving access to care for people who inject drugs: Qualitative evaluation of project ITTREAT-An integrated community hepatitis C service.

Achieving hepatitis C virus (HCV) elimination by 2030 requires an increased linkage to care for people who inject drugs (PWID). Project ITTREAT was established to mitigate barriers to HCV care by providing an integrated service within a local drug and alcohol treatment centre. This study aimed to explore the experiences of clients and staff involved in Project ITTREAT and assess the facilitators and barriers to a community-based HCV service. Between October 2014 and April 2016, drug and alcohol treatment attendees were interviewed using one-to-one semi-structured interviews. Drug and alcohol treatment staff took part in focus groups. All data were recorded, transcribed verbatim and analysed using thematic content analysis. Fifteen drug and alcohol treatment attendees with current/previous HCV infection were interviewed, and 15 staff members contributed across two focus groups. Drug and alcohol treatment staff and attendees reported that Project ITTREAT facilitated access to HCV care by mitigating previous negative hospital-based experiences. Other key facilitators were positive narratives around HCV care, and drug and alcohol treatment attendees being well engaged in their drug/alcohol recovery. Barriers included a lack of stability in drug and alcohol treatment attendees, negative discourse around testing/treatment and stigma associated with attending the drug and alcohol treatment to access HCV treatment in some who had successfully achieved drug rehabilitation. Our findings indicate the positive impact of an integrated and personalized community-based service delivered by a dedicated hepatitis nurse. This played a crucial role in reducing barriers to HCV care for PWID. Our work also highlights areas for future investment including non-DAT-based community services and increasing awareness of new treatments amongst this cohort.

Global prevalence of HCV and/or HBV coinfections among people who inject drugs and female sex workers who live with HIV/AIDS: a systematic review and meta-analysis.

Coinfections of hepatitis C virus (HCV) and/or hepatitis B virus (HBV) with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) are associated with high morbidity and mortality and poor prognosis. The main objective of this study was to evaluate the prevalence of HCV and/or HBV coinfections among people who inject drugs (PWID) and female sex workers (FSWs) who live with HIV/AIDS worldwide. Data sources were searched from January 2008 to October 2018 in different databases, including PubMed, Scopus, Web of Science, Embase, and Ovid. Data were analyzed in Stata 14 software using the Metaprop command. The results showed that the prevalence of HCV among PWID and FSWs with HIV/AIDS was 72% (95% CI: 59%-83%) and 40% (95% CI: 0%-94%), respectively. The prevalence of HBV among PWID and FSWs with HIV/AIDS was 8% (95% CI: 5%-13%) and 2% (95% CI: 0%-7%), respectively, and the prevalence of HCV/HBV in PWID with HIV/AIDS was 11% (95% CI: 7%-15%). The highest prevalence of HCV was observed in PWID in the Eastern Mediterranean and Europe regions, and the lowest was observed in the Africa region. The South-East Asia region had the highest prevalence of HBV among PWID, and the Africa region had the lowest prevalence. The high prevalence of HCV coinfection among PWID and FSWs with HIV/AIDS was an alarming health problem and requires appropriate interventions. Therefore, considering that these populations are key populations for HCV elimination, it is recommended to screen them regularly for HCV. In addition, harm reduction and HBV vaccination should be carefully considered.

Prevalence and risk factors associated with HIV/hepatitis B and HIV/hepatitis C co-infections among people who inject drugs in Mozambique.

BACKGROUND: There is scare information about HIV co-infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) among People Who Inject Drugs (PWID) in Mozambique. This information is critical to ensure the treatment necessary to decrease the progression of liver disease and the transmission of both HIV and hepatitis. We assess the prevalence of HIV, HBV and HCV co-infections as well as associated risk factors among PWID. METHODS: The first Bio-Behavioral Surveillance Survey was conducted in 2013-2014 among persons who self-reported to have ever injected drugs. Using respondent-driven sampling, PWID aged 18 years and older were recruited in two cross-sectional samples in Maputo and Nampula/Nacala, two large urban centers of Mozambique. Rapid screening of HIV, HBV (HBsAg) and HCV was performed on site. Data from participants in both cities were pooled to conduct RDS-weighted bivariate analyses with HIV/HBV and HIV/HCV co-infections as separate outcomes. Unweighted bivariate and multivariate logistic regression analyses were conducted to assess correlates of co-infection. RESULTS: Among 492 eligible PWID, 93.3% were male and median age was 32 years [IQR: 27-36]. HIV, HBV and HCV prevalence were respectively 44.9% (95% CI:37.6-52.3), 32.8% (95% CI:26.3-39.5) and 38.3 (95% CI:30.6-45.9). Co-infections of HIV/HBV, HIV/HCV and HIV/HBV/HCV were identified in 13.1% (95% CI:7.2-18.9), 29.5% (95% CI:22.2-36.8) and 9.2% (95% CI:3.7-14.7) of PWID, respectively. Older age, history of needle/syringe sharing and history of injection with used needle/syringe was associated with HIV/HBV co-infection. Living in Maputo city, have older age, history of needle/syringe sharing and history of injection with used needle/syringe was associated with HIV/HCV co-infection. CONCLUSION: There is a high burden of HBV and HCV among HIV-infected PWID in Mozambique. Our results highlight the need for targeted harm reduction interventions that include needle exchange programs and integrated services for the diagnosis and treatment of HIV, HBV and HCV to address these epidemics among PWID. Efforts should be made to strengthen ART coverage in the population as an important treatment strategy for both viruses.

A Global Meta-analysis of the Prevalence of HIV, Hepatitis C Virus, and Hepatitis B Virus Among People Who Inject Drugs-Do Gender-Based Differences Vary by Country-Level Indicators?

BACKGROUND: Women-specific factors exist that increases vulnerability to drug-related harms from injection drug use, including blood-borne viruses (BBVs), but gender-based differences in BBV prevalence have not been systematically examined. METHODS: We conducted meta-analyses to estimate country, regional, and global prevalence of serologically confirmed human immunodeficiency virus (HIV), hepatitis C virus (HCV; based on detection of anti-HCV antibody), and hepatitis B virus (HBV; based on detection of HBV surface antigen) in people who inject drugs (PWID), by gender. Gender-based differences in the BBV prevalence (calculated as the risk among women relative to the risk among men) were regressed on country-level prevalence and inequality measures (Gender inequality index, Human development index, Gini coefficient, and high, low or middle income of the country). RESULTS: Gender-based differences varied by countries and regions. HIV prevalence was higher among women than men in sub-Saharan Africa (relative risk [RR], 2.8; 95% confidence interval [CI], 1.8-4.4) and South Asia (RR, 1.7; 95% CI, 1.1-2.7); anti-HCV was lower among women in the Middle East and North Africa (RR, 0.6; 95% CI, .5-.7) and East and Southeast Asia (RR, 0.8; 95% CI, .7-.9). Gender-based differences varied with country-levels of the BBV prevalence in the general population, human development, and income distribution. CONCLUSION: HIV was more prevalent in women who inject drugs as compared to their male counterparts in some countries, but there is variation between and within regions. In countries where women are at higher risks, there is a need to develop gender-sensitive harm-reduction services for the particularly marginalized population of women who inject drugs.

Cross-genotype AR3-specific neutralizing antibodies confer long-term protection in injecting drug users after HCV clearance.

BACKGROUND & AIMS: In order to design an effective vaccine against hepatitis C virus (HCV) infection, it is necessary to understand immune protection. A number of broadly reactive neutralizing antibodies have been isolated from B cells of HCV-infected patients. However, it remains unclear whether B cells producing such antibodies contribute to HCV clearance and long-term immune protection against HCV. METHODS: We analysed the B cell repertoire of 13 injecting drug users from the Amsterdam Cohort Study, who were followed up for a median of 17.5 years after primary infection. Individuals were classified into 2 groups based on the outcome of HCV infection: 5 who became chronically infected either after primary infection or after reinfection, and 8 who were HCV RNA negative following spontaneous clearance of ≥1 HCV infection(s). From each individual, 10,000 CD27+IgG+B cells, collected 0.75 year after HCV infection, were cultured to characterize the antibody repertoire. RESULTS: Using a multiplex flow cytometry-based assay to study the antibody binding to E1E2 from genotype 1 to 6, we found that a high frequency of cross-genotype antibodies was associated with spontaneous clearance of 1 or multiple infections (p = 0.03). Epitope specificity of these cross-genotype antibodies was determined by alanine mutant scanning in 4 individuals who were HCV RNA negative following spontaneous clearance of 1 or multiple infections. Interestingly, the cross-genotype antibodies were mainly antigenic region 3 (AR3)-specific and showed cross-neutralizing activity against HCV. In addition to AR3 antibodies, 3 individuals developed antibodies recognizing antigenic region 4, of which 1 monoclonal antibody showed cross-neutralizing capacity. CONCLUSIONS: Together, these data suggest that a strong B cell response producing cross-genotype and neutralizing antibodies, especially targeting AR3, contributes to HCV clearance and long-term immune protection against HCV. LAY SUMMARY: Although effective treatments against hepatitis C virus (HCV) are available, 500,000 people die from liver disease caused by HCV each year and approximately 1.75 million people are newly infected. This could be prevented by a vaccine. To design a vaccine against HCV, more insight into the role of antibodies in the protection against HCV infection is needed. In a cohort of injecting drug users, we found that antibodies interfering with virus cell entry, and recognizing multiple HCV genotypes, conferred long-term protection against chronic HCV infection.

Response to direct-acting antiviral therapy among ongoing drug users and people receiving opioid substitution therapy.

BACKGROUND & AIMS: People who inject drugs (PWID) and are on opioid agonist therapy (OAT) might have lower adherence to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) and, therefore, lower rates of sustained virologic response (SVR). Because of this, we compared the SVR rates to interferon-free DAA combinations in individuals receiving OAT and those not receiving OAT in a real-world setting. METHODS: The HEPAVIR-DAA cohort, recruiting HIV/HCV-coinfected patients (NCT02057003), and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are ongoing prospective multicenter cohorts of patients receiving DAAs in clinical practice. We compared SVR 12 weeks after treatment (SVR12) in non-drug users and PWID, including those receiving or not receiving OAT. Intention-to-treat and per protocol analyses were performed. RESULTS: Overall, 1,752 patients started interferon-free DAA treatment. By intention-to-treat analysis, 778 (95%, 95% CI 93%-96%) never injectors, 673 (92%, 95% CI 89%-93%) PWID not on OAT and 177 (89%, 95% CI 83%-92%) PWID on OAT achieved SVR12 (p = 0.002). SVR12 rates for ongoing drug users (with or without OAT) were 68 (79%) compared with 1,548 (95%) for non-drug users (p <0.001). Among ongoing drug users, 15 (17%) were lost-to-follow-up, and 3 (3.5%) became reinfected. In the per protocol analysis, 97% never injectors, 95% PWID not on OAT and 95% PWID on OAT achieved SVR12 (p = 0.246). After adjustment, ongoing drug use was associated with SVR12 (intention-to-treat) and OAT use was not. CONCLUSIONS: HCV-infected PWID achieve high SVR12 rates with DAAs whether they are on OAT or not, but their response rates are lower than those of patients who never used drugs. This is mainly attributable to more frequent loss to follow-up. Accounting for active drug use during DAA therapy nearly closed the gap in SVR rates between the study groups. LAY SUMMARY: Patients with hepatitis C virus infection who are on opioid agonist therapy can achieve high cure rates with current treatments. The use of illicit drugs during treatment can drive drop-outs and reduce cure rates. However, hepatitis C can be cured in most of those using drugs who complete treatment and follow-up. Clinical trial number: HEPAVIR-DAA cohort, NCT02057003; GEHEP-MONO cohort, NCT02333292.

The case for a universal hepatitis C vaccine to achieve hepatitis C elimination.

BACKGROUND: The introduction of highly effective direct-acting antiviral (DAA) therapy for hepatitis C has led to calls to eliminate it as a public health threat through treatment-as-prevention. Recent studies suggest it is possible to develop a vaccine to prevent hepatitis C. Using a mathematical model, we examined the potential impact of a hepatitis C vaccine on the feasibility and cost of achieving the global WHO elimination target of an 80% reduction in incidence by 2030 in the era of DAA treatment. METHODS: The model was calibrated to 167 countries and included two population groups (people who inject drugs (PWID) and the general community), features of the care cascade, and the coverage of health systems to deliver services. Projections were made for 2018-2030. RESULTS: The optimal incidence reduction strategy was to implement test and treat programmes among PWID, and in settings with high levels of community transmission undertake screening and treatment of the general population. With a vaccine available, the optimal strategy was to include vaccination within test and treat programmes, in addition to vaccinating adolescents in settings with high levels of community transmission. Of the 167 countries modelled, between 0 and 48 could achieve an 80% reduction in incidence without a vaccine. This increased to 15-113 countries if a 75% efficacious vaccine with a 10-year duration of protection were available. If a vaccination course cost US$200, vaccine use reduced the cost of elimination for 66 countries (40%) by an aggregate of US$7.4 (US$6.6-8.2) billion. For a US$50 per course vaccine, this increased to a US$9.8 (US$8.7-10.8) billion cost reduction across 78 countries (47%). CONCLUSIONS: These findings strongly support the case for hepatitis C vaccine development as an urgent public health need, to ensure hepatitis C elimination is achievable and at substantially reduced costs for a majority of countries.

Change in injecting behaviour among people treated for hepatitis C virus: The role of intimate partnerships.

Injecting behaviour in people who inject drugs is the main risk factor for hepatitis C virus (HCV) infection. Psychosocial factors such as having a partner who injects drugs and living with other drug users have been associated with increases in injecting risk behaviour. This study aimed to investigate changes in injecting behaviour during treatment for HCV infection whilst exploring the role of psychosocial factors on patients' injecting behaviour. Eradicate-C was a single-centred clinical trial (ISRCTN27564683) investigating the effectiveness of HCV treatment within the injecting drug-using population between 2012 and 2017. A total of 94 participants completed up to 24 weeks of treatment, with social and behavioural measures taken at different intervals throughout treatment. Data for 84 participants were analysed retrospectively to explore mechanisms of potential behavioural changes which had occurred during treatment. Injecting frequency reduced significantly between baseline (week 1) and every 4-weekly interval until week 26. Not being on opiate substitution therapy (OST) was associated with a statistically significant decrease in injecting frequency, χ2 (1) = 10.412, P = 0.001, as was having a partner who also used drugs, in particular when that partner was also on treatment for HCV infection, Z = -2.312, P = 0.021. Treating a hard-to-reach population for HCV infection is not only possible, but also bears health benefits beyond treatment of HCV alone. Enrolling couples on HCV treatment when partners are sero-concordant has shown enhanced benefits for reduction in injecting behaviour. Implications for practice are discussed.

HIV Incidence, Prevalence, and Undiagnosed Infections in U.S. Men Who Have Sex With Men.

Background: HIV infection is a persistent health concern in the United States, and men who have sex with men (MSM) continue to be the most affected population. Objective: To estimate HIV incidence and prevalence and the percentage of undiagnosed HIV infections overall and among MSM. Design: Cross-sectional analysis. Setting: National HIV Surveillance System. Participants: Persons aged 13 years or older with diagnosed HIV infection. Measurements: Data on HIV diagnoses and the first CD4 test result after diagnosis were used to model HIV incidence and prevalence and the percentage of undiagnosed HIV infections from 2008 to 2015 on the basis of a well-characterized CD4 depletion model. Results: Modeled HIV incidence decreased 14.8% overall, from 45 200 infections in 2008 to 38 500 in 2015, and among all transmission risk groups except MSM. The incidence of HIV increased 3.1% (95% CI, 1.6% to 4.5%) per year among Hispanic/Latino MSM (6300 infections in 2008, 7900 in 2015), decreased 2.7% (CI, -3.8% to -1.5%) per year among white MSM (8800 infections in 2008, 7100 in 2015), and remained stable among black MSM at about 10 000 infections. The incidence decreased by 3.0% (CI, -4.2% to -1.8%) per year among MSM aged 13 to 24 years and by 4.7% (CI, -6.2% to -3.1%) per year among those aged 35 to 44 years. Among MSM aged 25 to 34 years, HIV incidence increased 5.7% (CI, 4.4% to 7.0%) per year and among MSM aged 55 years and older, HIV increased 4.1% (CI, 0.8% to 7.4%). The percentage of undiagnosed HIV infections was higher among black, Hispanic/Latino, and younger MSM than white and older MSM, respectively. Limitation: Assumptions of the CD4 depletion model and variability of CD4 values. Conclusion: Expansion of HIV screening to reduce undiagnosed infections and increased access to care and treatment to achieve viral suppression are critical to reduce HIV transmission. Access to prevention methods, such as condoms and preexposure prophylaxis, also is needed, particularly among MSM of color and young MSM. Primary Funding Source: None.

Recent and Rapid Transmission of HIV Among People Who Inject Drugs in Scotland Revealed Through Phylogenetic Analysis.

Background: Harm reduction has dramatically reduced HIV incidence among people who inject drugs (PWID). In Glasgow, Scotland, <10 infections/year have been diagnosed among PWID since the mid-1990s. However, in 2015 a sharp rise in diagnoses was noted among PWID; many were subtype C with 2 identical drug-resistant mutations and some displayed low avidity, suggesting the infections were linked and recent. Methods: We collected Scottish pol sequences and identified closely related sequences from public databases. Genetic linkage was ascertained among 228 Scottish, 1820 UK, and 524 global sequences. The outbreak cluster was extracted to estimate epidemic parameters. Results: All 104 outbreak sequences originated from Scotland and contained E138A and V179E. Mean genetic distance was <1% and mean time between transmissions was 6.7 months. The average number of onward transmissions consistently exceeded 1, indicating that spread was ongoing. Conclusions: In contrast to other recent HIV outbreaks among PWID, harm reduction services were not clearly reduced in Scotland. Nonetheless, the high proportion of individuals with a history of homelessness (45%) suggests that services were inadequate for those in precarious living situations. The high prevalence of hepatitis C (>90%) is indicative of sharing of injecting equipment. Monitoring the epidemic phylogenetically in real time may accelerate public health action.

Hepatitis D Viremia Among Injection Drug Users in San Francisco.

People who inject drugs (PWID) are commonly exposed to hepatitis B virus (HBV) and hepatitis D virus (HDV). We evaluated the prevalence of HDV viremia among hepatitis B surface antigen (HBsAg)-positive PWID (n = 73) using a new quantitative microarray antibody capture (Q-MAC) assay, HDV western blot, and HDV RNA. HDV Q-MAC performed well in this cohort: anti-HDV, 100% sensitivity and specificity; HDV viremia, 61.5% sensitivity and 100% specificity. Hepatitis D viremia was present in 35.6% of HBsAg-positive participants and was more common in those with resolved compared to chronic hepatitis C (5.1% vs 0.6%; adjusted odds ratio, 9.80; P < .0001).

Cost-Effectiveness of One-Time Hepatitis C Screening Strategies Among Adolescents and Young Adults in Primary Care Settings.

Background: High hepatitis C virus (HCV) rates have been reported in young people who inject drugs (PWID). We evaluated the clinical benefit and cost-effectiveness of testing among youth seen in communities with a high overall number of reported HCV cases. Methods: We developed a decision analytic model to project quality-adjusted life years (QALYs), costs (2016 US$), and incremental cost-effectiveness ratios (ICERs) of 9 strategies for 1-time testing among 15- to 30-year-olds seen at urban community health centers. Strategies differed in 3 ways: targeted vs routine testing, rapid finger stick vs standard venipuncture, and ordered by physician vs by counselor/tester using standing orders. We performed deterministic and probabilistic sensitivity analyses (PSA) to evaluate uncertainty. Results: Compared to targeted risk-based testing (current standard of care), routine testing increased the lifetime medical cost by $80 and discounted QALYs by 0.0013 per person. Across all strategies, rapid testing provided higher QALYs at a lower cost per QALY gained and was always preferred. Counselor-initiated routine rapid testing was associated with an ICER of $71000/QALY gained. Results were sensitive to offer and result receipt rates. Counselor-initiated routine rapid testing was cost-effective (ICER <$100000/QALY) unless the prevalence of PWID was <0.59%, HCV prevalence among PWID was <16%, reinfection rate was >26 cases per 100 person-years, or reflex confirmatory testing followed all reactive venipuncture diagnostics. In PSA, routine rapid testing was the optimal strategy in 90% of simulations. Conclusions: Routine rapid HCV testing among 15- to 30-year-olds may be cost-effective when the prevalence of PWID is >0.59%.

Hepatitis C virus infection among illicit drug users in an archipelago of the Amazon.

Hepatitis C virus (HCV) infection causes acute and chronic liver disease and may lead to cirrhosis, liver failure or hepatocellular carcinoma. The behavior of illicit drug users (DUs) typically exposes them to risks of viral infection. In the Brazilian Amazon region, a number of studies have identified high rates of drug use among adolescents, and a high prevalence of HBV infection in DUs, disseminated by sexual and parenteral activities. However, the epidemiological scenario of HCV infection in the region is still poorly understood. This study determined the prevalence, genotypes, and risk factors for HCV infection among DUs of the Marajó Archipelago. This cross-sectional study collected samples and epidemiological information from DUs in 11 municipalities. The diagnosis was established by EIA and real-time PCR, and the samples were genotyped by multiplex real time PCR. The data were analyzed by simple and multiple logistical regression. In 466 DUs, 28.3% had anti-HCV antibodies, and 25.5% had HCV-RNA. In 92 injecting drug users, 88.0% had anti-HCV antibodies, and 80.4% had HCV-RNA. Genotypes 1 and 3 were detected, with three cases of mixed infections. The multivariate analysis indicated associations of HCV infection with age (≥ 35 years), tattoos, intravenous drug use, shared use of injection equipment, and the daily and long-term (> 3 years) use of illicit drugs. These findings will contribute to the development of effective measures for the prevention of HCV infection among Brazilian DUs, as well as its general population.

Confirmation of HCV viremia using HCV RNA and core antigen testing on dried blood spot in HIV infected peoples who inject drugs in Vietnam.

BACKGROUND: Nucleic acid tests performed on blood samples collected on Dried Blood Spot (DBS) and detection of HCV core antigen (HCVcAg) are two approaches that may facilitate access to HCV diagnosis in low and middle incomes countries. In this study we evaluate HCV RNA and HCV antigen testing on DBS in HIV/HCV co-infected peoples who inject drugs in Vietnam. METHOD: One hundred and four HIV/HCV seropositive patients managed in outpatient care at the Haiphong Viet Tiep hospital were included in this study from February to March, 2014 (ANRS 12262 study). RESULTS: Eighty-six subjects were tested positive for HCV RNA in serum, median (IQR): 6.9 log10 IU/ml (5.6-7.4 log10 IU/ml). Genotypes consisted of 57 G1 (69%), 3 G3 (4%), and 22 G6 (27%). HCV RNA was detected on DBS specimens in 79 out 86 subjects with chronic hepatitis C (sensitivity 92.5%; 95% CI: 85.1-96.9%). HCV RNA level on DBS and serum was moderately correlated (r = 0.24; p = 0.05) suggesting a degradation of HCV RNA due to transportation and storage conditions. HCVcAg was detected in 75/86 dB specimens (sensitivity: 87.2%; 95% CI: 78.3-93.4%), with a strong positive relationship between DBS HCVcAg and serum HCV RNA levels (r = 0.80; P < 0.0001). CONCLUSIONS: Quantification of HCVcAg on DBS appears to benefit from substantial stability under prolonged storage conditions but with a lower analytical sensitivity compared to DBS HCV RNA testing. Detection of HCV RNA on DBS is an interesting approach for confirming viral replication in HCV seropositive persons but the impact of pre-analytical conditions on the integrity of HCV RNA needs to be controlled.

Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs.

BACKGROUND: Next-generation metagenomic sequencing (NGMS) has opened new frontiers in microbial discovery but has been clinically characterized in only a few settings. OBJECTIVE: To explore the plasma virome of persons who inject drugs and to characterize the sensitivity and accuracy of NGMS compared with quantitative clinical standards. DESIGN: Longitudinal and cross-sectional studies. SETTING: A clinical trial (ClinicalTrials.gov: NCT01285050) and a well-characterized cohort study of persons who have injected drugs. PARTICIPANTS: Persons co-infected with hepatitis C virus (HCV) and HIV. MEASUREMENTS: Viral nucleic acid in plasma by NGMS and quantitative polymerase chain reaction (PCR). RESULTS: Next-generation metagenomic sequencing generated a total of 600 million reads, which included the expected HIV and HCV RNA sequences. HIV and HCV reads were consistently identified only when samples contained more than 10 000 copies/mL or IU/mL, respectively, as determined by quantitative PCR. A novel RNA virus, human hepegivirus-1 (HHpgV-1), was also detected by NGMS in 4 samples from 2 persons in the clinical trial. Through use of a quantitative PCR assay for HHpgV-1, infection was also detected in 17 (10.9%) of 156 members of a cohort of persons who injected drugs. In these persons, HHpgV-1 viremia persisted for a median of at least 4538 days and was associated with detection of other bloodborne viruses, such as HCV RNA and SEN virus D. LIMITATION: The medical importance of HHpgV-1 infection is unknown. CONCLUSION: Although NGMS is insensitive for detection of viruses with relatively low plasma nucleic acid concentrations, it may have broad potential for discovery of new viral infections of possible medical importance, such as HHpgV-1. PRIMARY FUNDING SOURCE: National Institutes of Health.

A comparison of two biological markers of recent hepatitis C virus (HCV) infection: implications for the monitoring of interventions and strategies to reduce HCV transmission among people who inject drugs.

BackgroundMonitoring hepatitis C virus (HCV) incidence is important for assessing intervention impact. Longitudinal studies of people who inject drugs (PWID), using repeated biological tests, are costly; alternatively, incidence can be estimated using biological markers of recent infection in cross-sectional studies.AimWe aimed to compare incidence estimates obtained from two different biological markers of recent infection in a cross-sectional study to inform monitoring approaches for HCV elimination strategies.MethodSamples from an unlinked anonymous bio-behavioural survey of PWID were tested for two recent infection markers: HCV RNA with anti-HCV negative ('RNA') and low-avidity anti-HCV with HCV RNA present ('avidity'). These two markers were used separately and in combination to estimate HCV incidence.ResultsBetween 2011 and 2013, 2,816 anti-HIV-negative PWID (25% female) who had injected during the preceding year were either HCV-negative or had one of the two markers of recent infection: 57 (2.0%) had the RNA marker and 90 (3.2%) the avidity marker. The two markers had similar distributions of risk and demographic factors. Pooled estimated incidence was 12.3 per 100 person-years (pyrs) (95% credible interval: 8.8-17.0) and not significantly different to avidity-only (p = 0.865) and RNA-only (p = 0.691) estimates. However, the RNA marker is limited by its short duration before anti-HCV seroconversion and the avidity marker by uncertainty around its duration.ConclusionBoth markers have utility in monitoring HCV incidence among PWID. When HCV transmission is high, one marker may provide an accurate estimate of incidence; when it is low or decreasing, a combination may be required.

MEASUREMENT OF PERSONAL RISK BEHAVI-OR IN OCCUPATIONAL RISK STUDIES AMONG HEALTH CARE WORKERS.

Risky behaviours, particularly illegal and heavily stigmatized behaviours, are difficult to measure through self-report in both high risk groups and the general population. Underreporting can result in substantially biased estimates of non-injection drug use (IDU) risk of hepatitis C virus (HCV) infection. We hypothesized that asking about the existence of social networks injection drug use may be a useful marker of IDU. A cross-sectional survey of physicians and nurses was conducted in seven hospitals in Georgia. Based on survey responses participants were categorized into three IDU risk groups: ever used injecting drugs (Self IDU), reported a friend, family member or colleague used injecting drugs (Associate IDU), or reported neither (No IDU). Testing on anti-HCV was done using third generation ELISA methods. Both unadjusted and adjusted prevalence ratios between IDU risk groups and HCV prevalence were estimated. Of the 1312 (82.2%) participants, 10 (0.8%), 75 (5.7%), and 1227 (93.5%) were categorized as Self IDU, Associate IDU and No IDU, respectively; with HCV prevalence of 20%, 9.3% and 4.6%, respectively (p=0.016). The association was due primarily to women's reports. Those who reported some IDU risk were more likely to report other personal risk behaviors (e.g., multiple sex partners) and occupational risk behaviors (e.g., frequent exposure to blood and body fluids). This study represents a start of measurement development by assessing the potential usefulness of a marker to measure of IDU. Improved measurement of stigmatized behaviors is needed for confounding adjustment to improve estimates of occupational risks of blood-borne infections.

HLA-Bw4 80(T) and multiple HLA-Bw4 copies combined with KIR3DL1 associate with spontaneous clearance of HCV infection in people who inject drugs.

BACKGROUND & AIMS: Natural killer (NK) cell function is regulated by inhibitory and activating receptors including killer cell immunoglobulin-like receptors (KIRs). Here, we analyzed the impact of different KIR/KIR-ligand genotypes on the outcome of hepatitis C virus (HCV) infection in people who inject drugs (PWID). METHODS: KIR/KIR-ligand genotypes associated with spontaneous clearance of HCV infection were identified in a cohort of PWID from Germany (n=266) and further validated in a second anti-HCV positive cohort of PWID recruited in North America (n=342). NK cells of PWID and healthy donors were functionally characterized according to their KIR/KIR-ligand genotype by flow cytometry. RESULTS: Multivariate logistic regression analysis revealed that KIR3DL1/HLA-Bw4 80(T) was associated with spontaneous clearance of HCV infection in PWID, which was confirmed in the PWID cohort from North America. Compared with PWID with detectable HCV RNA, the frequency of individuals with multiple HLA-Bw4 alleles was significantly higher in anti-HCV positive PWID with resolved HCV infection (29.7% vs. 15.2%; p=0.0229) and in anti-HCV seronegative PWID (39.2%; p=0.0006). KIR3DL1+ NK cells from HLA-Bw4 80(T)-positive PWID showed superior functionality compared to HLA-Bw4 80(I)-positive PWID. This differential impact was not observed in healthy donors; however, the HLA-Bw4 copy number strongly correlated with the functionality of KIR3DL1+ NK cells. CONCLUSIONS: HLA-Bw4-80(T) and multiple HLA-Bw4 copies in combination with KIR3DL1 are associated with protection against chronic hepatitis C in PWID by distinct mechanisms. Better licensing of KIR3DL1+ NK cells in the presence of multiple HLA-Bw4 copies is beneficial prior to seroconversion whereas HLA-Bw4 80(T) may be beneficial during acute hepatitis C. Lay summary: Natural killer (NK) cells are part of the innate immune system and are regulated by a complex network of activating and inhibiting receptors. The regulating receptor-ligand pairs of an individual are genetically determined. Here, we identified a particular set of ligand and receptor genes that are associated with better functionality of NK cells and better outcome upon exposure to HCV in a high-risk group.