Risk Factors Associated with Hepatitis C Subtypes and the Evolutionary History of Subtype 1a in Mexico.

The Hepatitis C Virus (HCV), with its diverse genotypes and subtypes, has significantly impacted the health of millions of people worldwide. Analyzing the risk factors is essential to understanding the spread of the disease and developing appropriate prevention strategies. This study aimed to identify risk factors associated with HCV subtype transmission and calculate the emergence time of subtype 1a in Mexico. A cross-sectional study was conducted from January 2014 to December 2018, involving 260 HCV-infected adults. HCV infection was confirmed via Enzyme-Linked Immunosorbent Assay, and viral load was measured by real-time PCR. Genotyping/subtyping tools were the Line Probe Assay and Sanger sequencing of the non-structural region 5B (NS5B). The most frequent HCV subtype was 1a (58.5%), followed by subtypes 1b (19.2%), 3a (13.1%), 2b (5.4%), 2a/2c (2.7%), 2a (0.8%), and 4a (0.4%). Intravenous drug use and tattoos were significant risk factors for subtypes 1a and 3a, while hemodialysis and blood transfusion were linked with subtype 1b. For the evolutionary analysis, 73 high-quality DNA sequences of the HCV subtype 1a NS5B region were used, employing a Bayesian coalescent analysis approach. This analysis suggested that subtype 1a was introduced to Mexico in 1976, followed by a diversification event in the mid-1980s. An exponential increase in cases was observed from 1998 to 2006, stabilizing by 2014. In conclusion, this study found that HCV subtypes follow distinct transmission routes, emphasizing the need for targeted prevention strategies. Additionally, the findings provide valuable insights into the origin of HCV subtype 1a. By analyzing the history, risk factors, and dynamics of the HCV epidemic, we have identified these measures: limiting the harm of intravenous drug trafficking, enhancing medical training and infrastructure, and ensuring universal access to antiviral treatments. The successful implementation of these strategies could lead to an HCV-free future in Mexico.

Polysubstance Use and Related Risk Behaviors among People Who Inject Drugs in Kenya Preparing for Hepatitis C Virus Treatment.

Polysubstance use (PSU), injection drug use (IDU), and equipment sharing are associated with bloodborne infection (BBI) transmission risk, particularly Hepatitis C Virus (HCV), yet data on PSU in low- and middle-income countries (LMICs) is limited. We report on baseline PSU, medication-assisted treatment (MAT) engagement, and motivation to reduce IDU among 95 people who inject drugs (PWID) who accessed needle and syringe programs (NSP) in Nairobi and Coastal Kenya prior to HCV treatment. Bivariate and multivariate logistic regression were used to examine the associations between PSU and behaviors that confer HCV transmission and acquisition risks. Most participants (70.5%) reported PSU in the last 30 days, and one-third (35.8%) reported PSU exclusive to just heroin and cannabis use. Common combinations were heroin and cannabis (49.3%), and heroin, cannabis, and bugizi (flunitrazepam) (29.9%). Participants at baseline were receiving MAT (69.5%), already stopped or reduced IDU (30.5%), and were HIV-positive (40%). PSU was significantly associated with IDU (p = 0.008) and the number of times (p = 0.016) and days (p = 0.007) injected in the last 30 days. Participants reported high PSU and equipment sharing, despite high MAT engagement. While co-locating BBI treatment within existing harm reduction services is necessary to promote uptake and curb re-infection, tailored services may be needed to address PSU, particularly in LMICs.

Injection drug use and sexually transmitted infections among men who have sex with men: A retrospective cohort study at an HIV/AIDS referral hospital in Tokyo, 2013-2022.

Men who have sex with men (MSM) who use injection drugs (MSM-IDU) are at high risk of sexually transmitted infections (STIs), but the long-term incidence is unclear. We conducted a single-centre retrospective cohort study using the clinical records of non-haemophilia men with human immunodeficiency virus (HIV) who visited the Institute of Medical Science, the University of Tokyo (IMSUT) Hospital, located in Tokyo, Japan, from 2013 to 2022. We analysed 575 patients including 62 heterosexual males and 513 MSM patients, of whom 6.8% (35/513) were injection drug use (IDU). Compared to non-IDU MSM, MSM-IDU had a higher incidence of hepatitis C virus (HCV) (44.8 vs 3.5 /1,000 person-years (PY); incidence rate ratio (IRR) [95% confidence interval (95% CI)], 12.8 [5.5-29.3], p < 0.001) and syphilis (113.8 vs 53.3 /1,000 PY; IRR, 2.1 [1.4-3.1], p < 0.001). The incidence of other symptomatic STIs (amoebiasis, chlamydia, and gonorrhoea infections) was <4/1,000 PY. In multivariable Poisson regression analysis, HCV incidence was associated with MSM (IRR, 1.8 × 106 [9.9 × 105-3.4 × 106], p < 0.001), IDU (IRR, 10.1 [4.0-25.6], p < 0.001), and syphilis infection during the study period (IRR, 25.0 [1.2-518.3]/time/year, p < 0.001). Among men with HIV, the prevalence of IDU in MSM and the long-term incidence of STIs in MSM-IDU were high. IDU and sexual contact are important modes of transmission of HCV among HIV-infected MSM in Tokyo.

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.

BACKGROUND: 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. METHODS: 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%. RESULTS: 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. CONCLUSIONS: We estimate that HCV incidence will decline by >80% over 2015-2030 among ever MSM-IDU in San Francisco, achieving the WHO target.

Novel Circovirus in Blood from Intravenous Drug Users, Yunnan, China.

We identified a novel circovirus (human-associated circovirus 2 [HuCV2]) from the blood of 2 intravenous drug users in China who were infected with HIV-1, hepatitis C virus, or both. HuCV2 is most closely related to porcine circovirus 3. Our findings underscore the risk for HuCV2 and other emerging viruses among this population.

Incidence of hepatitis C virus infection among people living with HIV: An Egyptian cohort study.

Background: Egypt used to have one of the highest hepatitis C virus (HCV) infection prevalence rates worldwide, with an estimated HCV prevalence of around 4.5% to 6.7%. Objectives: To determine the HCV infection incidence rate amid Egyptian patients living with HIV. Method: A total of 460 HIV-positive patients were recruited in a retrospective cohort study from Imbaba Fever Hospital, Cairo, between January 2016 and March 2019. The patients had a negative baseline and at least one other HCV antibody test. Hepatitis C virus antibody testing was done by antibody sandwich third-generation enzyme-linked immunosorbent assay. The hepatitis C virus infection incidence rate among HIV-infected patients was calculated using the person-time incidence rate. Results: Two hundred and eighteen patients were finally included: 146 (31.7%) patients were excluded for having a positive baseline HCV Ab result and 96 patients were excluded for not having a follow-up HCV Ab test. Eighteen patients had HCV seroconversion (8.3%), achieving an incidence rate of 4.06 cases per 100 person-years (95% confidence interval: 3.87-4.24). Injection drug use (IDU) was the commonest risk factor among seroconverters, with an HCV incidence rate of 7.08 cases per 100 person-years. Injection drug use history was reported in 83.3% of the seroconverters and in only 47.2% of non-seroconverters; P = 0.005. Conclusion: Egyptian HIV-infected patients show a high incidence rate of HCV infection especially among those who have a history of IDU. Accordingly, attention should be paid for prevention, screening and timely treatment of HCV in patients infected with HIV. What this study adds: The demonstration of a high HCV infection incidence rate among HIV-infected patients and shows the need for screening and prevention in this population.

Myenteric Neurons Do Not Replicate in Small Intestine Under Normal Physiological Conditions in Adult Mouse.

BACKGROUND & AIMS: The enteric nervous system (ENS) is the largest part of the peripheral nervous system; moreover, abnormal ENS development and function are associated with multiple human pathologies. Data from several groups suggest that under normal physiological conditions in adult animals, enteric nerve cells do not replicate. A study by Kulkarni et al in 2017 challenged this view and proposed that nearly 70% of enteric neurons in the myenteric ganglia are born in 1 week. The authors of this study suggested that differences in DNA labelling times and DNA denaturation conditions might explain discrepancies with previous reports. Previous studies were carried out using different conditions and labelling techniques in various regions of the gastrointestinal tract; thus, conclusions have remained elusive. METHODS: Here, we have eliminated those variables by analyzing the whole small intestine using the reagents and conditions that Kulkarni et al used. To exclude variables related to immunohistochemistry, we carried out parallel experiments with "click chemistry"-based detection of DNA replication. RESULTS: Although proliferation was readily detected in the epithelium, we found no evidence of neuronal replication in the myenteric ganglia. CONCLUSIONS: We conclude that within 1 week under normal physiological conditions, myenteric neurons in the small intestine do not replicate.

High-Risk Injection-Related Practices Associated with anti-HCV Positivity among Young Adults Seeking Services in Three Small Cities in Wisconsin.

BACKGROUND: Hepatitis C virus (HCV) infection has been increasing among people who inject drugs (PWID), younger than 30 years, and living in rural or suburban areas. We examined injection-related behaviors of young PWID to determine factors associated with HCV infection. METHODS: From September 2013-May 2015, respondent-driven and snowball sampling were used in 3 suburban areas of Wisconsin to recruit PWID 18-29 years who reported injection drug use in the previous 12 months. Participants were tested for HCV antibody (anti-HCV) and reported injection-related behaviors/practices via self-administered computer-based survey. We calculated anti-HCV prevalence and assessed associated factors using multivariable logistic regression. RESULTS: Forty-two percent (117/280) of participants were male, 83% (231/280) were white, and median age was 23 years. Overall HCV prevalence was 33%, but HCV prevalence among males was 39%. Adjusting for age, sex, race/ethnicity, education, relationship status, insurance status and income, anti-HCV positivity was associated with higher injection frequency (> 100 times in the past six months) (aOR = 3.07; 95% Confidence Interval (95% CI): 1.72-5.45), ever shared syringes (aOR = 5.15; 95% CI: 2.52-10.51), past week/last use receptive rinse water sharing (aOR = 1.88; 95% CI: 1.06-3.33), past week/last use receptive filter sharing (aOR = 3.25; 95% CI: 1.61-6.54), reusing syringes (aOR = 1.91, 95% CI: 1.08-3.37), history of overdose (aOR = 8.82; 95% CI: 2.26-3.95), and having ever injected another PWID (aOR = 8.82; 95%CI 3.94-19.76). DISCUSSION: Anti-HCV positivity is associated with high-risk injection practices. Young PWID would benefit from access to evidence-based interventions that reduce their risk of infection, link those infected to HCV treatment, and provide education to reduce further transmission.

Hepatitis C antibody prevalence, correlates and barriers to care among people who inject drugs in Central California.

Hepatitis C (HCV) infection among people who inject drugs (PWID) is a major public health concern. We examined correlates of HCV antibody (anti-HCV) seropositivity and characteristics of prior HCV testing and treatment among PWID in Fresno, California, which has among the highest prevalence of injection drug use (IDU) in the United States. We surveyed 494 peer-recruited PWID (≥18 years of age) in 2016 about their experiences with HCV testing and treatment, and conducted HCV and HIV antibody testing for all participants. Bivariate analyses and multivariable logistic regressions were used to identify correlates of anti-HCV seropositivity. A majority (65%) tested positive for anti-HCV, with 32% of those being unaware of their HCV status. Anti-HCV seroprevalence was independently and positively associated with older age (AOR = 1.11 per year, 95% CI = 1.06, 1.17), years injecting (AOR = 1.08 per year, 95% CI = 1.03, 1.13), distributive syringe sharing (AOR = 2.76, 95% CI = 1.29, 5.94), having syringes confiscated by police (AOR = 2.65, 95% CI = 1.22, 5.74), ever trading sex (AOR = 3.51, 95% CI = 1.40, 8.81) and negatively associated with being Black/African American (non-Hispanic) (AOR = 0.06, 95% CI = 0.01, 0.47). Prior HCV testing was associated with older age, ever getting syringes from a syringe services program, and having interactions with police. For those aware of their anti-HCV seropositivity, only 11% had initiated treatment; reasons for not seeing a physician regarding diagnosis included not feeling sick (23%), currently using drugs/alcohol (19%) and not knowing where to go for HCV medical care (19%). Our findings highlight the importance of expanding community-based access to sterile syringes alongside HCV testing and treatment services, particularly at syringe service programs where PWID may be more comfortable seeking testing and treatment.

The Effectiveness of Low Dead Space Syringes for Reducing the Risk of Hepatitis C Virus Acquisition Among People Who Inject Drugs: Findings From a National Survey in England, Wales, and Northern Ireland.

Syringes with attached needles (termed fixed low dead space syringes [LDSS]) retain less blood following injection than syringes with detachable needles, but evidence on them reducing blood-borne virus transmission among people who inject drugs (PWID) is lacking. Utilizing the UK Unlinked Anonymous Monitoring cross-sectional bio-behavioral surveys among PWID for 2016/18/19 (n = 1429), we showed that always using fixed LDSS was associated with 76% lower likelihood (adjusted odds ratio  = 0.24, 95% confidence interval [CI]: .08-.67) of recent hepatitis C virus infection (RNA-positive and antibody-negative) among antibody-negative PWID compared to using any syringes with detachable needles.

Prevalence of HIV infection among non-elderly individuals with hepatitis C in Japan: a population-based cohort study using a health insurance claim data.

BACKGROUND: Hepatitis C virus (HCV) has been mainly transmitted through injection drug use, but recently, sexual transmission among men who have sex with men (MSM), which is also a major route of HIV transmission, is increasing. However, the prevalence of HIV and the incidence of other sexually transmitted infections (STIs) among HCV patients have been rarely reported. METHODS: Using a healthcare insurance claim data of employees and their dependents covering seven-million people in Japan, we evaluated HIV prevalence among HCV patients aged 20-59 years. Hemophilia patients were excluded. HIV and HCV were defined by registered diagnoses and receiving viral RNA testing. The time course of HCV and HIV infections was analyzed. Incidences of syphilis, amebiasis, chlamydia, gonorrhea, hepatitis A, and hepatitis B were assessed. RESULTS: From April 2012 to August 2018, 6,422 HCV patients were identified. HIV prevalence was 0.48% (31/6422, 95% CI [confidence interval]: 0.33-0.68%). HIV was diagnosed after HCV in 3.2% (1/31), before HCV in 58.1% (18/31), and concurrently in 38.7% (12/31). Compared with HCV patients without HIV infection, HCV/HIV co-infected patients were younger (median age, 37 vs 51 years, p < 0.001), more likely to be male (30/31 [96.8%] vs 3059/6391 [47.9%], p < 0.001), more likely to have other STIs (38.7% [12/31] vs 0.9% [56/6391], p < 0.001), and live in Tokyo, the most populous capital city in Japan (67.7% [21/31] vs 11.6% [742/6391], p < 0.001). In Tokyo, the HIV prevalence among 20-30 s male with HCV was 18.6% (13/70; 95% CI, 10.3-29.7%). CONCLUSIONS: HIV prevalence among young male HCV patients was very high in Tokyo. HCV/HIV co-infected patients were more likely to acquire HIV before HCV, which is a known feature of MSM. They also had a higher incidence of STIs. These findings suggest that HCV might be prevalent as an STI among MSM particularly in Tokyo.

A community-based study of abscess self-treatment and barriers to medical care among people who inject drugs in the United States.

Skin and soft tissue infections (SSTIs) are the most common medical complication of injection drug use in the United States, though little work has been done assessing SSTI treatment among people who inject drugs (PWID). We examined past-3-month abscess characteristics, treatment utilization, and barriers to medical treatment among N = 494 community-recruited PWID. We used descriptive statistics to determine the frequencies of self-treatment and medical treatment for their most recent past-3-month abscess as well as barriers to seeking medical treatment. We then used bivariate and multivariate logistic regression to identify factors associated with having an abscess in the past 3 months. Overall, 67% of participating PWID ever had an abscess and 23% had one in the past 3 months. Only 29% got medical treatment for their most recent abscess whereas 79% self-treated. Methods for self-treatment included pressing the pus out (81%), applying a hot compress (79%), and applying hydrogen peroxide (67%). Most (91%) self-treated abscesses healed without further intervention. Barriers to medical treatment included long wait times (56%), being afraid to go (49%), and not wanting to be identified as a PWID (46%). Factors associated independently with having an abscess in the past 3 months were injecting purposely into muscle tissue (adjusted odds ratio [AOR] = 2.64), having difficulty finding a vein (AOR = 2.08), and sharing injection preparation equipment (AOR = 1.74). Our findings emphasize the importance of expanding community-based access to SSTI education and treatment services, particularly at syringe service programs where PWID may be more comfortable seeking resources.

The bioavailability time of commonly used thymidine analogues after intraperitoneal delivery in mice: labeling kinetics in vivo and clearance from blood serum.

Detection of synthetic thymidine analogues after their incorporation into replicating DNA during the S-phase of the cell cycle is a widely exploited methodology for evaluating proliferative activity, tracing dividing and post-mitotic cells, and determining cell-cycle parameters both in vitro and in vivo. To produce valid quantitative readouts for in vivo experiments with single intraperitoneal delivery of a particular nucleotide, it is necessary to determine the time interval during which a synthetic thymidine analogue can be incorporated into newly synthesized DNA, and the time by which the nucleotide is cleared from the blood serum. To date, using a variety of methods, only the bioavailability time of tritiated thymidine and 5-bromo-2'-deoxyuridine (BrdU) have been evaluated. Recent advances in double- and triple-S-phase labeling using 5-iodo-2'-deoxyuridine (IdU), 5-chloro-2'-deoxyuridine (CldU), and 5-ethynyl-2'-deoxyuridine (EdU) have raised the question of the bioavailability time of these modified nucleotides. Here, we examined their labeling kinetics in vivo and evaluated label clearance from blood serum after single intraperitoneal delivery to mice at doses equimolar to the saturation dose of BrdU (150 mg/kg). We found that under these conditions, all the examined thymidine analogues exhibit similar labeling kinetics and clearance rates from the blood serum. Our results indicate that all thymidine analogues delivered at the indicated doses have similar bioavailability times (approximately 1 h). Our findings are significant for the practical use of multiple S-phase labeling with any combinations of BrdU, IdU, CldU, and EdU and for obtaining valid labeling readouts.

Hepatitis C-related knowledge, attitudes and perceived risk behaviours among people who inject drugs in Kenya: A qualitative study.

Despite disproportionately high rates of Hepatitis C (HCV) among people who inject drugs (PWID) in low- and middle-income countries (LMICs), understanding of HCV-related knowledge, attitudes and perceived risk behaviours among this population remains limited. We aimed to elucidate knowledge, attitudes and experiences that could minimise transmission risk and maximise HCV treatment engagement among PWID in Kenya following the integration of HCV screening and education with needle and syringe programmes in drop-in-centres (DICs). We recruited 40 PWID with chronic HCV attending DICs in Nairobi and Coastal Kenya. Semi-structured interviews revealed a general understanding of HCV and awareness of HCV risk behaviours among participants; however, many felt limited control over their transmission risk due to factors such as 'local doctors', or individuals who perform a high volume of high-risk injections. Financial barriers, distance to clinic, poor health status and HCV-related stigma were all noted as barriers to HCV treatment. In conclusion, basic knowledge of and motivation for HCV treatment among PWID accessing DICs in Kenya was high; however, structural barriers and stigma complicate access to care. Local education programmes can address knowledge gaps, and behavioural and structural interventions can maximise the impact of HCV care in LMICs.

Deep Vein Thrombosis in Intravenous Drug Users: An Invisible Global Health Burden.

The prevalence of intravenous drug use has increased in the past decade and it represents an important risk factor for deep vein thrombosis. Intravenous drug use is a global problem, with the main culprit being heroin. Peer pressure and poverty in high-risk groups such as sex workers, females, and young adults raise the risk of intravenous drug use, which expresses itself in the form of venous thromboembolism eventually. Deep vein thrombosis typically manifests itself eight years after the initial intravenous drug administration, rendering it a silent killer. Aiming to review and summarize existing articles in this context, we performed an exhaustive literature search online on PubMed and Google Scholar indexes using the keywords "Deep Venous Thrombosis (DVT)" and "Intravenous Drug Users (IVDU)." English articles that addressed epidemiology, pathogenesis, clinical manifestations, diagnosis, differential diagnosis, management, and outcomes of DVT, including those in IVDU, were selected and analyzed. The pathogenesis of DVT development in IVDU is mainly attributed to the interplay of trauma to the vessel by repeated injection and the injected drug itself. The right-sided femoral vein is the most common vein affected. Prevalent clinical presentations include local pain, swelling, and redness with typical systemic symptoms including fever, cough, dyspnea, and chest pain on top of addiction features. There appeared to be a delay in reporting symptoms, which was most likely due to the social stigma attached to IVDU. There are over 50 conditions that present with swollen and painful limbs comparable to DVT in IVDU, making precise diagnosis critical for timely treatment. Venous ultrasound is the method of choice for diagnosing DVT. Extended anticoagulant therapy with low-molecular-weight heparin combined with warfarin is the recommended treatment. Intravenous drug abusers having DVT are affected by multiple complications and poorer outcomes such as slower recovery, recurrent venous thromboembolism (VTE), and a longer hospital stay, which put them at higher risk of morbidity, mortality, reduced productivity, and economic burden.

Performance of models to predict hepatocellular carcinoma risk among UK patients with cirrhosis and cured HCV infection.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) prediction models can inform clinical decisions about HCC screening provided their predictions are robust. We conducted an external validation of 6 HCC prediction models for UK patients with cirrhosis and a HCV virological cure. METHODS: Patients with cirrhosis and cured HCV were identified from the Scotland HCV clinical database (N = 2,139) and the STratified medicine to Optimise Treatment of Hepatitis C Virus (STOP-HCV) study (N = 606). We calculated patient values for 4 competing non-genetic HCC prediction models, plus 2 genetic models (for the STOP-HCV cohort only). Follow-up began at the date of sustained virological response (SVR) achievement. HCC diagnoses were identified through linkage to nation-wide cancer, hospitalisation, and mortality registries. We compared discrimination and calibration measures between prediction models. RESULTS: Mean follow-up was 3.4-3.9 years, with 118 (Scotland) and 40 (STOP-HCV) incident HCCs observed. The age-male sex-ALBI-platelet count score (aMAP) model showed the best discrimination; for example, the Concordance index (C-index) in the Scottish cohort was 0.77 (95% CI 0.73-0.81). However, for all models, discrimination varied by cohort (being better for the Scottish cohort) and by age (being better for younger patients). In addition, genetic models performed better in patients with HCV genotype 3. The observed 3-year HCC risk was 3.3% (95% CI 2.6-4.2) and 5.1% (3.5-7.0%) in the Scottish and STOP-HCV cohorts, respectively. These were most closely matched by aMAP, in which the mean predicted 3-year risk was 3.6% and 5.0% in the Scottish and STOP-HCV cohorts, respectively. CONCLUSIONS: aMAP was the best-performing model in terms of both discrimination and calibration and, therefore, should be used as a benchmark for rival models to surpass. This study underlines the opportunity for 'real-world' risk stratification in patients with cirrhosis and cured HCV. However, auxiliary research is needed to help translate an HCC risk prediction into an HCC-screening decision. LAY SUMMARY: Patients with cirrhosis and cured HCV are at high risk of developing liver cancer, although the risk varies substantially from one patient to the next. Risk calculator tools can alert clinicians to patients at high risk and thereby influence decision-making. In this study, we tested the performance of 6 risk calculators in more than 2,500 patients with cirrhosis and cured HCV. We show that some risk calculators are considerably better than others. Overall, we found that the 'aMAP' calculator worked the best, but more work is needed to convert predictions into clinical decisions.

Outcomes of Real-World Integrated HCV Microelimination for People Who Inject Drugs: An expansion of the Punjab Model.

BACKGROUND: The prevalence of chronic hepatitis C (CHC) in People Who Inject Drugs (PWID) is 8-10% as compared to 3·6% in the general population in Punjab, India. We assessed the real-world efficacy and safety of free-of-charge generic direct-acting antivirals (DAAs), sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir)±ribavirin in the microelimination of CHC in PWID in a public health setting. METHODS: An integrated care team at 25 sites provided algorithm based DAAs treatment to PWID supervised by telemedicine clinics between 18th June 2016 and 31st July 2019. The primary endpoint was sustained virological response at 12 weeks (SVR-12); the secondary endpoints were treatment completion, adherence, safety, and adverse events. ClinicalTrials.gov number: NCT01110447. FINDINGS: We enrolled 3477 PWID (87·2% men; mean age 33·6±12·5 years; 83·8% rural; 6·8% compensated cirrhosis). While 2280 (65·5%) patients completed treatment, 1978 patients completed 12 weeks of follow up for SVR-12. SVR-12 was achieved in 91·1% of patients per protocol, 49.5% as per intention to treat (ITT) and 90·1% in a modified ITT analysis. Of 546 (15·7%) patients with treatment interruptions, 99 (19·7%) could be traced to test for SVR-12 with a cure rate of 77·8%. There were no major adverse events or consequent treatment discontinuation. INTERPRETATION: Integrated care of PWID with CHC with DAAs is safe and effective. Measures for reducing treatment interruptions will further improve outcomes. FUNDING: The Government of the state of Punjab, India under the Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF) project, funds the project.

Mathematical modelling for assessing the impact of intervention strategies on HIV/AIDS high risk group population dynamics.

The global economic importance of HIV/AIDS and inadequacy of the literature dealing with deterministic model on control strategy of HIV/AIDS that captures factors responsible for the spread of the disease in low income country is one among other factors responsible for the ill management of the disease in an endemic population. Thus, this study focuses on a novel deterministic mathematical model to assess the impact of intervention strategies on high risk group with drug quitters special case and drug users who are sexually active (duality case). Backward bifurcation, positivity of the model variables, sensitivity analysis, global stability of DFE and EEP are used to investigate the qualitative structure of the model. It was established that the duality effect of the force of infection spur by intravenous drug users who sexually active (IDUSA-special case) are responsible for backward (IDUSA) in the endemic population. Sensitivity analysis on IDU and MSM group shows that 20% decrease of the susceptible population of both classes will attenuate the transmission dynamics by 7.4% and 2.6% of the MSM and IDU class respectively. Further simulation, using demographic and epidemiological data available in Nigeria shows that the disease burden reduces with universal strategy than combined strategy.

Predictors of having naloxone in urban and rural Oregon findings from NHBS and the OR-HOPE study.

PURPOSE: Naloxone is an opioid antagonist that can be effectively administered by bystanders to prevent overdose. We determined the proportion of people who had naloxone and identified predictors of naloxone ownership among two samples of people who inject drugs (PWID) who use opioids in Portland and rural Western Oregon. BASIC PROCEDURES: We used data from participants in Portland's National HIV Behavioral Surveillance (NHBS, N = 477) and the Oregon HIV/Hepatitis and Opioid Prevention and Engagement Study (OR-HOPE, N = 133). For each sample, we determined the proportion of participants who had naloxone and estimated unadjusted and adjusted relative risk of having naloxone associated with participant characteristics. MAIN FINDINGS: Sixty one percent of NHBS and 30 % of OR-HOPE participants had naloxone. In adjusted analysis, having naloxone was associated with female gender, injecting goofballs (compared to heroin alone), housing stability, and overdose training in the urban NHBS sample, and having naloxone was associated with drug of choice, frequency of injection, and race in the rural OR-HOPE sample. In both samples, having naloxone was crudely associated with SSP use, but this was attenuated after adjustment. PRINCIPAL CONCLUSIONS: Naloxone ownership was insufficient and highly variable among two samples of PWID who use opioids in Oregon. People who use methamphetamine, males, and people experiencing homelessness may be at increased risk for not having naloxone and SSP may play a key role in improving access.