High Hepatitis C Virus Incidence Research Articles

Incidence and Prevalence of Hepatitis C Virus Among HIV-Negative Gay and Bisexual Men Using HIV Pre-exposure Prophylaxis (PrEP): A Systematic Review and Meta-analysis.

Gay and bisexual men using HIV pre-exposure prophylaxis (PrEP) are at increased risk for sexually transmissible infections. Hepatitis C virus (HCV) risk among PrEP users is less clear. We explored HCV prevalence and incidence among cohorts of gay and bisexual men using PrEP and sources of heterogeneity across studies. This was a systematic review and meta-analysis of open-label PrEP studies to April 2022 reporting HCV prevalence at baseline or incidence during follow-up among gay and bisexual men using PrEP. Pooled prevalence and incidence estimates were calculated using random-effects meta-analysis, and subgroup analyses were performed by study- and country-level characteristics, including availability of HCV direct-acting antiviral (DAA) therapy at time of study. Twenty-four studies from 9 countries were included, with a total sample of 24 733 gay and bisexual men. Pooled HCV antibody baseline prevalence was 0.97% (95% CI, 0.63%-1.31%), and pooled HCV RNA baseline prevalence was 0.38% (95% CI, 0.19%-0.56%). Among 19 studies reporting HCV incidence, incidence ranged from 0.0 to 2.93/100 person-years (py); the pooled estimate was 0.83/100py (95% CI, 0.55-1.11). HCV incidence was higher in 12 studies that began follow-up before broad DAA availability (1.27/100py) than in 8 studies that began follow-up after broad DAA availability (0.34/100py) and higher in studies in Europe compared with North America and Australia. Early reports of high HCV incidence among PrEP-using cohorts likely reflect enrollment of individuals based on specific risk-based eligibility criteria for smaller studies and enrollment before DAA scale-up. In contexts where both DAAs and PrEP have been implemented at scale, studies report lower HCV incidence. PrEP-specific HCV testing guidelines should be guided by local epidemiology.

Impact of HCV Testing and Treatment on HCV Transmission Among Men Who Have Sex With Men and Who Inject Drugs in San Francisco: A Modelling Analysis.

Men who have sex with men who ever injected drugs (ever MSM-IDU) carry a high hepatitis C virus (HCV) burden. We estimated whether current HCV testing and treatment in San Francisco can achieve the 2030 World Health Organization (WHO) HCV elimination target on HCV incidence among ever MSM-IDU. A dynamic HCV/HIV transmission model among MSM was calibrated to San Francisco data, including HCV antibody (15.5%, 2011) and HIV prevalence (32.8%, 2017) among ever MSM-IDU. MSM had high HCV testing (79%-86% ever tested, 2011-2019) and diagnosed MSM had high HCV treatment (65% ever treated, 2018). Following coronavirus disease 2019 (COVID-19)-related lockdowns, HCV testing and treatment decreased by 59%. Among all MSM, 43% of incident HCV infections in 2022 were IDU-related. Among ever MSM-IDU in 2015, HCV incidence was 1.2/100 person-years (95% credibility interval [CrI], 0.8-1.6). Assuming COVID-19-related declines in HCV testing/treatment persist until 2030, HCV incidence among ever MSM-IDU will decrease by 84.9% (95% CrI, 72.3%-90.8%) over 2015-2030. This decline is largely attributed to HCV testing and treatment (75.8%; 95% CrI, 66.7%-89.5%). Slightly greater decreases in HCV incidence (94%-95%) are projected if COVID-19 disruptions recover by 2025 or 2022. We estimate that HCV incidence will decline by >80% over 2015-2030 among ever MSM-IDU in San Francisco, achieving the WHO target.

Public health interventions, priority populations, and the impact of COVID-19 disruptions on hepatitis C elimination among people who have injected drugs in Montreal (Canada): A modeling study.

In Montreal (Canada), high hepatitis C virus (HCV) seroincidence (21 per 100 person-years in 2017) persists among people who have injected drugs (PWID) despite relatively high testing rates and coverage of needle and syringe programs (NSP) and opioid agonist therapy (OAT). We assessed the potential of interventions to achieve HCV elimination (80% incidence reduction and 65% reduction in HCV-related mortality between 2015 and 2030) in the context of COVID-19 disruptions among all PWID and PWID living with HIV. Using a dynamic model of HCV-HIV co-transmission, we simulated increases in NSP (from 82% to 95%) and OAT (from 33% to 40%) coverage, HCV testing (every 6 months), or treatment rate (100 per 100 person-years) starting in 2022 among all PWID and PWID living with HIV. We also modeled treatment scale-up among active PWID only (i.e., people who report injecting in the past six months). We reduced intervention levels in 2020-2021 due to COVID-19-related disruptions. Outcomes included HCV incidence, prevalence, and mortality, and proportions of averted chronic HCV infections and deaths. COVID-19-related disruptions could have caused temporary rebounds in HCV transmission. Further increasing NSP/OAT or HCV testing had little impact on incidence. Scaling-up treatment among all PWID achieved incidence and mortality targets among all PWID and PWID living with HIV. Focusing treatment on active PWID could achieve elimination, yet fewer projected deaths were averted (36% versus 48%). HCV treatment scale-up among all PWID will be required to eliminate HCV in high-incidence and prevalence settings. Achieving elimination by 2030 will entail concerted efforts to restore and enhance pre-pandemic levels of HCV prevention and care.

Establishing a framework towards monitoring HCV microelimination among men who have sex with men living with HIV in Germany: A modeling analysis.

Prior to direct-acting antivirals (DAAs), HCV incidence rose among men who have sex with men (MSM) living with HIV infection in Germany despite high hepatitis C virus (HCV) treatment rates. We establish a HCV elimination modeling framework to evaluate whether existing treatment rates can achieve the World Health Organization (WHO) incidence target among MSM living with HIV in Germany. To evaluate progress towards HCV elimination in Germany, we adapted a previously published HCV transmission model among MSM living with diagnosed HIV. We modelled HCV incidence and prevalence until 2030 (relative to 2015) under existing treatment and DAA scale-up and explored potential impacts of disruptions in treatment and behavioral risk reduction due to the COVID-19 pandemic. Continuing current treatment rates will result in stable HCV incidence among MSM living with HIV in Germany between 2015-2030. The WHO HCV incidence target is achievable under DAA scale-up to 100% treatment combined with treatment of those previously diagnosed and untreated (at a rate of 15%/year) and would result in greater reductions with early treatment (3 vs 6 months) reducing incidence from 4.0/100person-years to 0.8/100person-years by 2030. A 12-month disruption to HCV treatment (20% reduction) and risk behaviors (25%,50%,75% reduction) during the COVID-19 pandemic would result in a 15% relative increase in total HCV incidence in 2030 compared to that expected under the status quo. HCV elimination among MSM living with HIV in Germany requires further DAA scale-up among those newly diagnosed combined with efforts to treat those previously diagnosed but untreated. Prospective monitoring will establish whether Germany is on track for HCV microelimination.

Distribution and Incidence of Blood-Borne Infection among Blood Donors from Regional Transfusion Centers in Burkina Faso: A Comprehensive Study.

ABSTRACTThere is a high prevalence of blood-borne infections in West Africa. This study sought to determine the seroprevalence of blood-borne infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), HIV, and syphilis, in blood donors in Burkina Faso. Blood donors were recruited from 2009 to 2013 in four major cities in Burkina Faso of urban area (Ouagadougou) and rural area (Bobo Dioulasso, Fada N’Gourma, and Ouahigouya). Serology tests including hepatitis B surface antigen, anti-HCV, anti-HIV, and rapid plasma reagin test were used for screening and were confirmed with ELISA. Disease prevalence was calculated among first-time donors. Incidence and residual risk were calculated from repeat donors. There were 166,681 donors; 43,084 had ≥ 2 donations. The overall seroprevalence of HBV, HCV, HIV, and syphilis were 13.4%, 6.9%, 2.1%, and 2.4%, respectively. The incidence rates (IRs) of HBV, HCV, HIV, and syphilis infection were 2,433, 3,056, 1,121, and 1,287 per 100,000 person-years. There was lower seroprevalence of HBV and HCV in urban area than in rural area (12.9% versus 14.0%, P < 0.001; and 5.9% versus 8.0%, P < 0.001), and no difference in HIV (2.1% versus 2.1%, P = 0.25). The IRs of new HBV, HCV, HIV, and syphilis were 2.43, 3.06, 1.12, and 1.29 per 100,000 person-years, respectively. The residual risk was one per 268 donations for HBV, one per 181 donations for HCV, and one per 1,480 donations for HIV, respectively. In conclusion, this comprehensive study from four blood donation sites in Burkina Faso showed high HBV and HCV seroprevalence and incidence with high residual risk from blood donation.

Prevalence and incidence of hepatitis C virus infection in men who have sex with men: a systematic review and meta-analysis

WHO has set targets for hepatitis C virus (HCV) elimination by 2030. We did a global systematic review of HCV prevalence and incidence in men who have sex with men (MSM) to provide updated estimates that can guide community education and public health policy. We did a systematic review and meta-analysis of studies published and listed on MEDLINE or Embase between Jan 1, 2000, and Oct 31, 2019, including conference proceedings. Studies were eligible if they reported measures of HCV prevalence or HCV incidence (or both) among MSM. Studies that relied on participants' self-reported HCV status with no laboratory confirmation were excluded. Pooled HCV estimates in MSM were stratified by HIV status and by injecting drug use, then by WHO region and by income level. Random-effects meta-analysis was done to account for between-study heterogeneity and examined using the I2 statistic. Pooled HCV prevalence was also compared with HCV estimates in the general population and presented as prevalence ratios (PRs). In HIV-negative MSM, incidence estimates were stratified by use of HIV pre-exposure prophylaxis (PrEP). The systematic review was registered with PROSPERO, number CRD42020156262. Of 1221 publications identified, 194 were deemed to be eligible and included in the systematic review and meta-analysis. Overall, the pooled HCV prevalence in MSM was 3·4% (95% CI 2·8-4·0; I2=98·0%) and was highest in Africa (5·8%, 2·5-10·4) and South-East Asia (5·0%, 0·0-16·6). Globally, HCV prevalence was 1·5% (1·0-2·1) in HIV-negative MSM and 6·3% (5·3-7·5) in HIV-positive MSM. Compared with the general population, HCV prevalence was slightly higher in HIV-negative MSM (PR 1·58, 95% CI 1·14-2·01) and markedly higher (6·22, 5·14-7·29) in HIV-positive MSM. Pooled HCV prevalence was substantially higher in MSM who had ever injected drugs (30·2%, 22·0-39·0) or currently injected drugs (45·6%, 21·6-70·7) than in those who never injected drugs (2·7%, 2·0-3·6). In HIV-negative MSM, the pooled HCV incidence was 0·12 per 1000 person-years (95% CI 0·00-0·72) in individuals not on PrEP and 14·80 per 1000 person-years (9·65-20·95) in individuals on PrEP. HCV incidence in HIV-positive MSM was 8·46 per 1000 person-years (6·78-10·32). HIV-positive MSM are at substantially increased risk of HCV. Overall, HIV-negative MSM had a slightly higher prevalence of HCV than the general population but had a lower prevalence than HIV-positive MSM. High HCV incidence in more recent PrEP studies suggests that as PrEP use increases, greater HCV transmission might occur. HCV burden in MSM varies considerably by region, which is likely to be associated with variation in the prevalence of injecting drug use and HIV. World Health Organization.

314. Healthcare Providers’ Views on HCV Testing and Counseling Among Sexual Partners of Hepatitis C-Infected Persons

BackgroundCurrent hepatitis C virus (HCV) counseling guidelines from the Centers for Disease Control and Prevention (CDC) do not recommend that HCV-infected-patients notify their partners or encourage them to get tested. Because there is a small but present risk of HCV acquisition through sex, sexual partners should be encouraged to receive HCV counseling and testing. We aimed to assess healthcare professionals’ knowledge of and attitudes toward current counseling and testing recommendations for HCV-infected patients.MethodsA 15-question, anonymous survey was designed and distributed to a convenience sample of healthcare providers (MDs, NPs, PAs) who work with Brown University or Boston University-affiliated hospitals. Questionnaires included demographic information as well as questions regarding providers’ current counseling practices and knowledge of current recommendations for HCV counseling. Descriptive statistics were used to analyze the survey data.ResultsOf the 55 respondents (a 20% response rate), 73% believed that current CDC HCV testing guidelines already recommend partners of HCV-infected patients be tested for HCV infection. Furthermore, 80% of respondents believed recommendations should be revisited to explicitly include that HCV-infected patients encourage their partners to get tested. When counseling patients with HCV, 44% of respondents reported they always ask whether the patient’s partners have been tested for HCV and 42% reported they sometimes do. Similarly, 42% reported they always suggest that the HCV-infected patient’s partners be tested for HCV. If sufficient resources were available, 75% of respondents reported that they would support active partner notification for HCV during an HCV outbreak situation and 72% said they would support active partner notification in a non-outbreak situation where there is still high HCV incidence.ConclusionOur survey shows that healthcare providers believe that current HCV-counseling and testing recommendations could be revisited, with specific attention given to the promotion of HCV testing for partners of HCV-infected patients.Disclosures All authors: No reported disclosures.

1112 Hepatitis C Virus Infection in Young Adults - A Re-Emerging Problem

INTRODUCTION: Hepatitis C virus (HCV) infection is a major cause of life-threatening liver diseases worldwide. People born between 1945-1965 have been known to have high incidence of HCV. In recent years, increased rate of HCV infection is noted in the younger populations. This has been attributed to injection drug use, opioid addiction and perinatal transmission. It is paramount to understand the pattern of HCV transmission, disease severity and treatment rates in the young adults which can enable us to provide timely intervention and prevent detrimental liver complications. METHODS: Retrospective observational study including patients between 18 to 40 years who tested positive for HCV antibody between 2016-2017. Descriptive and statistical analyses were performed to evaluate prevalence of HCV, treatment rates and disease severity. Liver disease severity was calculated using Model of End Stage Liver Disease (MELD) and Child-Pugh Turcot (CTP) scores. RESULTS: A total of 507 patients who tested positive for HCV antibodies between 2016-2017 was evaluated. Of these, 83 (n = 83) patients between 18 to 40 years were included in this study. Prevalence of HCV was noted to be 16.4%. Majority of the population were African American (66%). An almost equal number of males and females (53% and 47%) were present. The incidence of smoking, alcohol use and IV drug use were 12%, 25% and 19% respectively. Majority had CTP score of 5-6 (87%) and rest had CTP score 7-9 (13%). Majority also had MELD &lt; 9 (60%) followed by MELD 10-19 (23%) and MELD 20-29 (17%). The MELD and CTP scores were lower compared to patients &gt;40 years of age with HCV. A small population had decompensated cirrhotic features of hepatic encephalopathy and ascites (7% and 2% respectively). A very low number of them Hepatitis B surface Ab positive (1%) and majority had not received treatment for HCV infection (90%). CONCLUSION: In this study we noted a high number of young adults between 18-40years of age infected with HCV, majority were HCV treatment naïve and had less advanced liver disease with low rates of liver cirrhosis, hepatic encephalopathy and low MELD and CTP scores. IVDU was low in our population in contrary to other data. Very low HBV vaccination rate was noted, indicating the high risk for HBV infection in this population. In conclusion, HCV in young adults is a growing problem and it is pivotal to increase awareness and study the disease and transmission patterns to adequately manage this issue and prevent liver complications.

Eliminating Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men in Berlin: A Modeling Analysis.

Despite high hepatitis C virus (HCV) treatment rates, HCV incidence among human immunodeficiency virus (HIV)-infected men who have sex with men (HIV-infected MSM) in Germany rose before HCV direct-acting antivirals (DAAs). We model what intervention can achieve the World Health Organization (WHO) elimination target of an 80% reduction in HCV incidence by 2030 among HIV-infected MSM in Berlin. An HCV transmission model among HIV-diagnosed MSM was calibrated to Berlin (rising HCV incidence and high rates of HCV testing and treatment). We modeled the HCV incidence among HIV-diagnosed MSM in Berlin until 2030 (relative to 2015 WHO baseline) under scenarios of DAA scale-up with or without behavior change (among HIV-diagnosed MSM and/or all MSM). Continuing current treatment rates will marginally reduce the HCV incidence among HIV-diagnosed MSM in Berlin by 2030. Scaling up DAA treatment rates, beginning in 2018, to 100% of newly diagnosed HCV infections within 3 months of diagnosis and 25% each year of previously diagnosed and untreated HCV infections could reduce the HCV incidence by 61% (95% confidence interval, 55.4%-66.7%) by 2030. The WHO target would likely be achieved by combining DAA scale-up with a 40% reduction in HCV transmission among HIV-diagnosed MSM and a 20% reduction among HIV-undiagnosed or HIV-uninfected MSM. HCV elimination among HIV-infected MSM in Berlin likely requires combining DAA scale-up with moderately effective behavioral interventions to reduce risk among all MSM.

Influence of social determinants of health and substance use characteristics on persons who use drugs pursuit of care for hepatitis C virus infection

BackgroundSocial determinants of health (SDOH), i.e., social, behavioral and environmental factors, are increasingly recognized for their important influence on health outcomes. Data are limited on the influence of SDOH, substance use characteristics, and their interactions on pursuit of hepatitis C virus (HCV) care among individuals with opioid use disorder (OUD). Linkage to HCV care remains low in this population despite high HCV prevalence and incidence. AimsTo investigate the influence of SDOH, substance use factors, and their interactions on HCV treatment uptake among OUD patients in a methadone treatment program. MethodsInformation on patient demographics, SDOH, substance use characteristics, and co-morbid medical conditions were obtained from the paper and electronic medical records of OUD patients on methadone. We applied multiple correspondence analysis, k-means algorithm, and logistic regression with least absolute shrinkage and selection operator penalty to identify variables and clusters associated with pursuit of HCV care. ResultsData from 161 patients (57% male, 60% Caucasian, mean age 45 years) were evaluated. Being employed, the absence of support systems, and a history of foster care were the strongest positive predictors of treatment pursuit. The use of crack/cocaine as the initial illicit substance, criminal activity without incarceration, and the absence of a family history of chemical dependency were the strongest negative predictors. We identified clusters among persons with OUD based upon their likelihood to pursue HCV management. ConclusionUtilizing data from the medical record, we were able to identify factors positively and negatively associated with linkage-to-care for HCV. We were also able to divide patients into clusters of factors associated with linkage-to-care for HCV. These results could be used to identify individuals with OUD based upon their readiness for HCV care.

Sexually transmitted hepatitis C infection: the evolving epidemic in HIV-positive and HIV-negative MSM.

The scale-up of direct-acting antiviral (DAA) therapy and introduction of preexposure prophylaxis (PrEP) has changed the epidemiology of sexually acquired hepatitis C virus (HCV) amongst HIV-positive and HIV-negative MSM. Sexually acquired HCV continues to occur predominantly amongst HIV-positive MSM. Despite an increased uptake of DAA therapy the incidence of acute HCV has not declined consistently amongst HIV-positive MSM, likely a result of high infection and reinfection rates. Increasing cases of sexually acquired HCV have been reported amongst HIV-negative MSM accessing PrEP. Despite a lower prevalence of HCV at baseline, HIV-negative MSM accessing PrEP have an equally high overall incidence of HCV compared with HIV-positive MSM during follow-up. Behavioural factors (high-risk sexual behaviours and sexualized drug use) appear to be driving this HCV epidemic amongst MSM and effective behavioural interventions and early identification of reinfections are essential to control the HCV epidemic amongst MSM. An improved understanding of the epidemiology of sexually acquired HCV will allow implementation of more effective public health interventions to control the transmission of HCV amongst HIV-positive and HIV-negative MSM.

Commentary on Grebely et al. (2019): Ending HCV epidemics among people who inject drugs.

The new direct-acting antiretroviral drugs for treating hepatitis C have generated considerable momentum for treating HCV infection among people who inject drugs and perhaps ‘ending the HCV epidemic’. There are, however, important epidemiological and behavior research problems that need to be addressed before ‘ending the HCV epidemic’ will be possible. The development of direct-acting antivirals (DAAs) that cure HCV infection in more than 90% of patients with minimal side effects has led to calls for ‘eliminating HCV infection’ or ‘ending HCV epidemics’ among people who inject drugs (PWID) 1. Some of the calls for eliminating HCV infection have included substantial allocations of new funds, e.g. New York State 2. Grebely et al. 3 have estimated the number and prevalence of people with a recent history (within past year) of injecting drug use who are living with hepatitis C virus (HCV) viremia and the proportion of people with recent injecting drug use among all people living with HCV infection at the global, regional and national levels. A major value of this study is its potential contribution as a baseline for ‘eliminating HCV’. While DAAs and the lessons from successfully controlling HIV among PWID in many areas 4 should certainly be useful in controlling HCV among PWID, the data presented in Grebely et al. illustrate that there is still a major amount of epidemiological and behavioral science that will be needed before ‘eliminating’ (or even ‘controlling’) HCV among PWID can be accomplished. First, what would ‘elimination/ending the epidemic’ of HCV among PWID look like? From early in the HIV epidemic among PWID, we had multiple examples, e.g. Glasgow, Scotland, Lund, Sweden, Sydney, Australia and Tacoma, WA, USA, where large-scale implementation of syringe access programs have kept HIV prevalence stable at less than 5% 5. The Grebely et al. data do not provide many (if any) examples of areas where HCV viremia has been stabilized at ‘ending the epidemic’ levels. Would 5% viremia in the local PWID population be a realistic goal? What sort of HCV combined prevention and care programs would be needed to stabilize HCV at 5% or less in a PWID population? Such a system would need to detect and treat existing cases of HCV infection as rapidly as new infections were occurring. Secondly, how will we develop better estimates of the size of PWID populations and the percentage of PWID who are HCV viremic? The uncertainty intervals in the Grebely et al. estimates are rather large, typically almost as large as the estimates themselves. Uncertainty in the estimates of the PWID population size and the percentage of PWID who are HCV viremic would create difficult problems for local officials who would have the task of allocating resources and planning logistical operations for rapidly scaling-up treatment for HCV-infected PWID. Thirdly, what new interventions can be developed to reduce HCV transmission behavior among viremic PWID? One of the important factors in HIV prevention was that PWID who learned that they were HIV-seropositive greatly reduced transmission behavior (passing their used needles and syringes to others) well before antiretroviral therapy (ART) was available 6. We have not yet seen the equivalent reductions in transmission behaviors among PWID who know that they are HCV-seropositive 7. How do we successfully encourage HCV viremic PWID to reduce transmission behavior? Fourthly, what interventions can be developed and implemented to reduce the very high HCV incidence rates among people who have recently begun injecting drugs 8? Many new injectors typically do not identify as ‘drug injectors’, and thus do not utilize HIV/HCV safer injection programs 9. Fifthly, what interventions will be implemented to reduce the rates that drug users transition to injecting drug use? There have been calls for more research on this topic 10, and there are current research studies addressing this subject. However, the objective should be to develop an evidence base for reducing initiation into injecting drug use that is comparable to the evidence base for medication assisted treatment and for syringe access programs. The new DAAs certainly give us the capability of treating very large numbers of HCV infected people who use drugs and greatly reduce morbidity and mortality, and programs to provide access to HCV treatment should be scaled-up in high-, middle- and low-income countries as quickly as feasible, and the additional research needed to learn how to ‘end HCV epidemics’ among PWID should be funded. Finally, and perhaps most importantly, while the above may be considered scientific tasks, it is important to emphasize that the research should be conducted in full collaboration with PWID and drug-user organizations. Such collaboration should not only greatly improve the quality of the research, but also greatly improve the likelihood that the findings will be incorporated into public health programs that could ‘end the HCV epidemic’ among people who use drugs. None.

Incidence and spontaneous clearance of hepatitis C virus (HCV) in people who inject drugs at the Stockholm Needle Exchange-Importance for HCV elimination.

The major transmission route for hepatitis C virus (HCV) is through sharing of unsterile injection equipment among people who inject drugs (PWID). The WHO strategy for HCV elimination by 2030 proposes increased efforts to treat PWID populations that drive the HCV epidemic. Among participants in the Stockholm needle exchange programme (NEP), the HCV prevalence is 60%. We aimed to study HCV incidence, spontaneous HCV clearance rate, and predictors associated with new HCV infections and reinfections in NEP participants. All 2320 patients enrolled in the programme between 8 April 2013 and 23 September 2016 were tested for HCV at baseline, and responded to a questionnaire regarding sociodemographic data and injection risk behaviour. Tests for HCV were repeated at an interval of 3-6months. The anti-HCV prevalence in the NEP participants at baseline was 77%, and the prevalence of HCV RNA was 57%. 24% of the anti-HCV positive were HCV RNA negative with a spontaneously cleared HCV infection. The overall HCV incidence rate was 22/100 PY. The HCV incidence rate in the HCV naive group was 26/100 PY, and in the spontaneously cleared group 19/100. Although there were no significant differences in becoming HCV infected between the two groups (31% vs 29%), the rate of spontaneous HCV clearance was significantly lower in the HCV naive group, 20% vs 44%, (P<0.05). A high HCV incidence rate was noted among the PWID indicating that treatment needs to be scaled up in conjunction with harm reduction measures to achieve HCV elimination goals set by WHO. This includes high coverage needle exchange programmes and effective addiction treatment for substance users, including opiate substitution treatment.

Estimate of vertical transmission of Hepatitis C virus in Pakistan in 2007 and 2012 birth cohorts.

Our results showed that one in 260 children born in Pakistan in 2007 and 2012 acquired HCV vertically. While currently no interventions during pregnancy and childbirth are recommended to reduce this risk, prevention, testing and treatment strategies should be considered to reduce the burden of vertical HCV infections among young children. Other routes of transmission appear to contribute the majority of HCV infections among children and must also be clarified and urgently addressed.

High hepatitis C incidence in relation to prescription opioid injection and poly-drug use: Assessing barriers to hepatitis C prevention

BackgroundPrescription opioid (PO) injection and poly-drug use have been associated with hepatitis C virus (HCV) infection among people who inject drugs (PWID). Poly-drug use is often a barrier to key HCV preventive programmes including opioid agonist treatment. The contribution of specific drug combinations to high HCV incidence in poly-drug users has not been assessed previously. Addressing this knowledge gap could enhance HCV treatment and prevention efforts. We examined the association between specific drugs and number of drugs used in addition to injected POs, and HCV seroconversion. MethodsPWID participating in a cohort study in Montréal (HEPCO), HCV-seronegative at baseline and followed between 2004 and 2013, were included. Data were collected by interview-administered questionnaires. Blood samples were tested for HCV new infections at each 3–6 month follow-up visit. Time-varying Cox regression models were utilized. ResultsOf 356 participants (81.5% males; mean age: 34.7 years), 123 (34.6%) reported injected POs in the past month at baseline. In univariate analyses, recent use of the following drugs was associated with HCV seroconversion: injected POs, injected cocaine, injected heroin, non-injected tranquilisers, and smoked crack/cocaine. The relative excess risk of HCV seroconversion due to interaction (RER1HR) was the highest for co-use of injected POs with the following substances: injected cocaine (RER1HR=3.44), smoked crack/cocaine (RER1HR=1.27), and non-injected tranquilisers (RER1HR=0.8). In addition, a significant linear trend (p<0.001) towards higher risk was observed with increasing the number of these three drugs used in combination with injected POs. ConclusionSpecific drugs and number of drugs used in addition to injected POs play a modulating role in the risk of HCV primary infection. Poly-drug use among people who inject POs has to be addressed in order to improve harm reduction programmes and reduce HCV transmission in this high-risk population.

Geographic Differences in Temporal Incidence Trends of Hepatitis C Virus Infection Among People Who Inject Drugs: The InC3 Collaboration.

We determined temporal trends (1985-2011) in hepatitis C virus (HCV) incidence and associated behavioral exposures for people who inject drugs (PWID) from the United States (Boston, Baltimore, and San Francisco), Canada (Montreal), the Netherlands (Amsterdam), and Australia (Sydney and Melbourne). Using population-based cohort data from HCV-negative PWID, we calculated overall and within-city HCV incidence trends, HCV rates by study enrollment period (1985-2011), and temporal trends in exposure behaviors. Poisson regression models estimated trends in HCV incidence over calendar-time. Survival models identified risk factors for HCV incidence across cities and estimated independent effects of city and calendar period on HCV infection risk. Among 1391 initially HCV-negative participants followed prospectively (1644.5 person-years of observation [PYO]), 371 HCV incident infections resulted in an overall incidence of 22.6 per 100 PYO (95% confidence interval [CI], 20.4-25.0). Incidence was highest and remained elevated in Baltimore (32.6/100 PYO), San Francisco (24.7/100 PYO), and Montreal (23.5/100 PYO), lowest in Melbourne and Amsterdam (7.5/100 PYO and 13.1/100 PYO, respectively), and moderate (21.4/100 PYO) in Sydney. Higher rates of syringe and equipment sharing and lower prevalence of opioid agonist therapy were associated with HCV incidence in cities with the highest incidence. Risk for infection dropped by 18% for every 3-year increase in calendar-time (adjusted hazard ratio, 0.8 [95% CI, .8-.9]) in the multivariable model. Differences in prevention strategies and injecting contexts may explain the ongoing high HCV incidence in these North American cities and emphasize the need for scale-up of opioid agonist therapy and increased coverage of needle and syringe programs in North America.

The effects of needle-sharing and opioid substitution therapy on incidence of hepatitis C virus infection and reinfection in people who inject drugs.

Although high hepatitis C virus (HCV) prevalence has been observed in people who inject drugs (PWID) for decades, research suggests incidence is falling. We examined whether PWIDs' use of opioid substitution therapy (OST) and their needle-and-syringe sharing behaviour explained HCV incidence. We assessed HCV incidence in 235 PWID in Melbourne, Australia, and performed discrete-time survival with needle-sharing and OST status as independent variables. HCV infection, reinfection and combined infection/reinfection incidences were 7·6 [95% confidence interval (CI) 4·8-11·9], 12·4 (95% CI 9·1-17·0) and 9·7 (95% CI 7·4-12·6) per 100 person-years, respectively. Needle-sharing was significantly associated with higher incidence of naive HCV infection [hazard ratio (HR) 4·9, 95% CI 1·3-17·7] but not reinfection (HR 1·85, 95% CI 0·79-4·32); however, a cross-model test suggested this difference was sample specific. Past month use of OST had non-significant protective effects against naive HCV infection and reinfection. Our data confirm previous evidence of greatly reduced HCV incidence in PWID, but not the significant protective effect of OST on HCV incidence detected in recent studies. Our findings reinforce the need for greater access to HCV testing and prevention services to accelerate the decline in incidence, and HCV treatment, management and support to limit reinfection.

Hepatitis C and HIV incidence and harm reduction program use in a conflict setting: an observational cohort of injecting drug users in Kabul, Afghanistan.

BackgroundArmed conflict may increase the risk of HIV and other pathogens among injecting drug users (IDUs); however, there are few prospective studies. This study aimed to measure incidence and potential predictors, including environmental events and needle and syringe distribution and collection program (NSP) use, of hepatitis C virus (HCV) and HIV among IDUs in Kabul, Afghanistan.MethodsConsenting adult IDUs completed interviews quarterly in year 1 and semi-annually in year 2 and HCV and HIV antibody testing semi-annually through the cohort period (November 2007–December 2009). Interviews detailed injecting and sexual risk behaviors, NSP service use, and conflict-associated displacement. Quarters with peak conflict or local displacement were identified based on literature review, and key events, including insurgent attacks and deaths, were reported with simple counts. Incidence and predictors of HCV and HIV were measured with Cox proportional hazards models.ResultsOf 483 IDUs enrolled, 385 completed one or more follow-up visits (483.8 person-years (p-y)). All participants were male with a median age of 28 years and a median duration of injecting of 2 years. Reported NSP use among the participants ranged from 59.9 to 70.5 % in the first year and was 48.4 and 55.4 % at 18 and 24 months, respectively. There were 41 confirmed deaths, with a crude death rate of 93.4/1000 p-y (95 % confidence interval (CI) 67.9–125) and overdose as the most common cause. HCV and HIV incidence were 35.6/100 p-y (95 % CI 28.3–44.6) and 1.5/100 p-y (95 % CI 0.6–3.3), respectively. Changing from injecting to smoking was protective for HCV acquisition (adjusted hazard ratio (AHR) = 0.53, 95 % CI 0.31–0.92), while duration of injecting (AHR = 1.09, 95 % CI 1.01–1.18/year) and sharing syringes (AHR = 10.09, 95 % CI 1.01–100.3) independently predicted HIV infection.ConclusionThere is high HCV incidence and high numbers of reported deaths among male Kabul IDUs despite relatively consistent levels of harm reduction program use; peak violence periods did not independently predict HCV and HIV risk. Programming should increase awareness of HCV transmission and overdose risks, prepare clients for harm reduction needs during conflict or other causes of displacement, and continue efforts to engage community and police force support.

Genotypic distribution of hepatitis C virus in Thailand and Southeast Asia.

The majority of hepatitis C virus (HCV) infection results in chronic infection, which can lead to liver cirrhosis and hepatocellular carcinoma. Global burden of hepatitis C virus (HCV) is estimated at 150 million individuals, or 3% of the world’s population. The distribution of the seven major genotypes of HCV varies with geographical regions. Since Asia has a high incidence of HCV, we assessed the distribution of HCV genotypes in Thailand and Southeast Asia. From 588 HCV-positive samples obtained throughout Thailand, we characterized the HCV 5’ untranslated region, Core, and NS5B regions by nested PCR. Nucleotide sequences obtained from both the Core and NS5B of these isolates were subjected to phylogenetic analysis, and genotypes were assigned using published reference genotypes. Results were compared to the epidemiological data of HCV genotypes identified within Southeast Asian. Among the HCV subtypes characterized in the Thai samples, subtype 3a was the most predominant (36.4%), followed by 1a (19.9%), 1b (12.6%), 3b (9.7%) and 2a (0.5%). While genotype 1 was prevalent throughout Thailand (27–36%), genotype 3 was more common in the south. Genotype 6 (20.9%) constituted subtype 6f (7.8%), 6n (7.7%), 6i (3.4%), 6j and 6m (0.7% each), 6c (0.3%), 6v and 6xa (0.2% each) and its prevalence was significantly lower in southern Thailand compared to the north and northeast (p = 0.027 and p = 0.030, respectively). Within Southeast Asia, high prevalence of genotype 6 occurred in northern countries such as Myanmar, Laos, and Vietnam, while genotype 3 was prevalent in Thailand and Malaysia. Island nations of Singapore, Indonesia and Philippines demonstrated prevalence of genotype 1. This study further provides regional HCV genotype information that may be useful in fostering sound public health policy and tracking future patterns of HCV spread.

Assessing the feasibility of hepatitis C virus vaccine trials: Results from the Hepatitis C Incidence and Transmission Study-community (HITS-c) vaccine preparedness study

Efficacy trials of preventive hepatitis C virus (HCV) vaccine candidates raise challenging scientific and ethical issues. Based on data from the first 3years of a community-based prospective observational study – the Hepatitis C Incidence and Transmission Study-community (HITS-c) – this paper examines the feasibility of conducting trials of candidate HCV vaccines with people who inject drugs (PWID) in Sydney, Australia. Of the 166 PWID confirmed HCV antibody negative and eligible for enrolment, 156 (94%) completed baseline procedures. Retention was high, with 89% of participants retained at 48weeks and 76% of participants completing at least 75% of study visits within 2weeks of schedule. The rate of primary HCV infection was 7.9/100py (95% CI 4.9, 12.7). Of the 17 incident cases, 16 completed at least one follow-up assessment and 12 (75%) had evidence of chronic viraemia with progression to chronic HCV infection estimated to be 6/100py. Power calculations suggest a chronic HCV infection rate of at least 12/100py (primary HCV infection rate 16/100py) will be required for stand-alone trials of highly efficacious candidates designed to prevent chronic infection. However, elevated primary HCV infection was observed among participants not receiving opioid substitution therapy who reported heroin as the main drug injected (26.9/100py, 95% CI 14.5, 50.0) and those who reported unstable housing (23.5/100py, 95% CI 7.6, 72.8), daily or more frequent injecting (22.7/100py, 95% CI 12.2, 42.2) and receptive syringe sharing (23.6/100py, 95% CI 9.8, 56.7) in the 6months prior to baseline. These data suggest that it is possible to recruit and retain at-risk PWID who adhere to study protocols and that modification of eligibility criteria may identify populations with sufficiently high HCV incidence. Results support the feasibility of large multi-centre HCV vaccine trials, including in the Australian setting.