Is the HCV-HIV co-infection prevalence amongst injecting drug users a marker for the level of sexual and injection related HIV transmission?

BACKGROUND: Amongst injecting drug users (IDUs), HIV is transmitted sexually and parenterally, but HCV is transmitted primarily parenterally. We assess and model the antibody prevalence of HCV amongst HIV-infected IDUs (denoted as HCV-HIV co-infection prevalence) and consider whether it proxies the degree of sexual HIV transmission amongst IDUs. METHODS: HIV, HCV and HCV-HIV co-infection prevalence data amongst IDU was reviewed. An HIV/HCV transmission model was adapted. Multivariate model uncertainty analyses determined whether the model's ability to replicate observed data trends required the inclusion of sexual HIV transmission. The correlation between the model's HCV-HIV co-infection prevalence and estimated proportion of HIV infections due to injecting was evaluated. RESULTS: The median HCV-HIV co-infection prevalence (prevalence of HCV amongst HIV-infected IDUs) was 90% across 195 estimates from 43 countries. High HCV-HIV co-infection prevalences (>80%) occur in most (75%) settings, but can be lower in settings with low HIV prevalence (0.75). The model without sexual HIV transmission reproduced some data trends but could not reproduce any epidemics with high HIV/HCV prevalence ratios (>0.85) or low HCV-HIV co-infection prevalence (10%. The model with sexual HIV transmission reproduced data trends more closely. The proportion of HIV infections due to injecting correlated with HCV-HIV co-infection prevalence; suggesting that up to 80/60/90%. CONCLUSION: Substantial sexual HIV transmission may occur in many IDU populations; HCV-HIV co-infection prevalence could signify its importance

by M Sprenger Rapid communications HIV and AIDS in the European Union, 2009 4

D Tubin-Delic, on behalf of the outbreak control team Surveillance and outbreak reports Control of a multi-hospital outbreak of KPC-producing Klebsiella pneumonia

Needle syringe programmes and opioid substitution therapy for preventing HCV transmission among people who inject drugs: findings from a Cochrane Review and meta-analysis.

AIMS: To estimate the effects of needle syringe programmes (NSP) and opioid substitution therapy (OST), alone or in combination, for preventing acquisition of Hepatitis C virus (HCV) in people who inject drugs (PWID). METHODS: Systematic review and meta-analysis. Bibliographic databases were searched for studies measuring concurrent exposure to current OST (within last 6 months) and/or NSP and HCV incidence among PWID. High NSP coverage was defined as regular NSP attendance or ≥100% coverage (receiving sufficient or greater number of needles/syringes per reported injecting frequency). Studies were assessed using the Cochrane risk of bias in non-randomised studies tool. Random effects models were used in meta-analysis. RESULTS: We identified 28 studies (n=6279) in North America (13), UK (5), Europe (4), Australia (5), and China (1). Studies were at moderate (2), serious (17) critical (7) and non-assessable risk of bias (2). Current OST is associated with 50% (risk ratio (RR) 0.50 95% CI 0.40-0.63) reduction in HCV acquisition risk, consistent across region and with low heterogeneity (I(2) =0, p=0.889). Weaker evidence was found for high NSP coverage (RR=0.79 95% CI 0.39-1.61) with high heterogeneity (I(2) =77%, p=0.002). After stratifying by region, high NSP coverage in Europe was associated with a 56% reduction in HCV acquisition risk (RR=0.44, 95% CI 0.24-0.80) with low heterogeneity (I(2) =12.3%, p=0.337) but not in North America (RR=1.58, I(2) =89.5%, p=<0.001). Combined OST/NSP is associated with a 76% reduction in HCV acquisition risk (RR=0.24 95% CI=0.07-0.89, I(2) =80% p=0.007). According to GRADE criteria, the evidence on OST and combined OST/NSP is low quality while NSP is very low. CONCLUSIONS: Opioid substitution therapy reduces risk of hepatitis C acquisition and is strengthened in combination with needle syringe programmes. There is weaker evidence for the impact of needle syringe programmes alone, although stronger evidence that high coverage is associated with reduced risk in Europe

An analysis of ethical issues in using wastewater analysis to monitor illicit drug use

New Zealand is considered to have unusual drug use patterns by international standards. However, this understanding has largely been obtained from social surveys where respondents self-report use. The aim of this paper is to conduct the first wastewater study of drug use in Auckland

Modelling the impact of a national scale-up of interventions on hepatitis C virus transmission among people who inject drugs in Scotland

BACKGROUND AND AIMS: To reduce hepatitis C virus (HCV) transmission among people who inject drugs (PWID), Scottish Government-funded national strategies, launched in 2008, promoted scaling-up opioid substitution therapy (OST) and needle and syringe provision (NSP), with some increases in HCV treatment. We test whether observed decreases in HCV incidence post-2008 can be attributed to this intervention scale-up. DESIGN: A dynamic HCV transmission model among PWID incorporating intervention scale-up and observed decreases in behavioural risk, calibrated to Scottish HCV prevalence and incidence data for 2008/09. SETTING: Scotland, UK. PARTICIPANTS: PWID. MEASUREMENTS: Model projections from 2008 to 2015 were compared with data to test whether they were consistent with observed decreases in HCV incidence among PWID while incorporating the observed intervention scale-up, and to determine the impact of scaling-up interventions on incidence. FINDINGS: Without fitting to epidemiological data post-2008/09, the model incorporating observed intervention scale-up agreed with observed decreases in HCV incidence among PWID between 2008 and 2015, suggesting that HCV incidence decreased by 61.3% [95% credibility interval (CrI) = 45.1-75.3%] from 14.2/100 person-years (py) (9.0-20.7) to 5.5/100 py (2.9-9.2). On average, each model fit lay within 84% (10.1/12) of the confidence bounds for the 12 incidence data points against which the model was compared. We estimate that scale-up of interventions (OST + NSP + HCV treatment) and decreases in high-risk behaviour from 2008 to 2015 resulted in a 33.9% (23.8-44.6%) decrease in incidence, with the remainder [27.4% (17.6-37.0%)] explained by historical changes in OST + NSP coverage and risk pre-2008. Projections suggest that scaling-up of all interventions post-2008 averted 1492 (657-2646) infections over 7 years, with 1016 (308-1996), 404 (150-836) and 72 (27-137) due to scale-up of OST + NSP, decreases in high-risk behaviour and HCV treatment, respectively. CONCLUSIONS: Most of the decline in hepatitis C virus (HCV) incidence in Scotland between 2008 and 2015 appears to be attributable to intervention scale-up (opioid substitution therapy and needle and syringe provision) due to government strategies on HCV and drugs

Determining the structure of the bacterial voltage-gated sodium channel NaChBac embedded in liposomes by cryo electron tomography and subtomogram averaging

Voltage-gated sodium channels shape action potentials that propagate signals along cells. When the membrane potential reaches a certain threshold, the channels open and allow sodium ions to flow through the membrane depolarizing it, followed by the deactivation of the channels. Opening and closing of the channels is important for cellular signalling and regulates various physiological processes in muscles, heart and brain. Mechanistic insights into the voltage-gated channels are difficult to achieve as the proteins are typically extracted from membranes for structural analysis which results in the loss of the transmembrane potential that regulates their activity. Here, we report the structural analysis of a bacterial voltage-gated sodium channel, NaChBac, reconstituted in liposomes under an electrochemical gradient by cryo electron tomography and subtomogram averaging. We show that the small channel, most of the residues of which are embedded in the membrane, can be localized using a genetically fused GFP. GFP can aid the initial alignment to an average resulting in a correct structure, but does not help for the final refinement. At a moderate resolution of ˜16 Å the structure of NaChBac in an unrestricted membrane bilayer is 10% wider than the structure of the purified protein previously solved in nanodiscs, suggesting the potential movement of the peripheral voltage-sensing domains. Our study explores the limits of structural analysis of membrane proteins in membranes

Acceso a servicios de salud en mujeres transgénero de la ciudad de Cali, Colombia

Introduction: Transgender population faces challenges in terms of guaranteeing the rights to health and an effective access to health services in every country. Objective: To describe and analyze the access to preventive, healing, specific care, and associated out-of-pocket health services for transgender women in Cali, Colombia. Methodology: An observational cross-sectional study with probability sampling. An adaptation of the Survey on Access to Health Services for Colombian Homes was applied to a total of 109 people who identified themselves as transgender, and all of them were over 18. A univariate analysis of all variables evaluated was carried out. Results: Although 71.6% of transgender women surveyed were covered by the health system, this percentage does not guarantee timely access to services. There is an institutional weakness regarding to the Health Promoting Entities (EPS) to promote preventive services; the access to consultation with a specialist and medicines had unfavorable results in opportunity and quality; also, the needs related to their gender identity or processes of corporal transformation are not treated. Discussion: As reported in other studies, for the population in general, the findings are coherent with the Colombian health system structure which is designed to invest resources in treating diseases but not preventing them. Conclusions: Differential care protocols are required given the risks for transgender people due to the lack of medical and psychosocial care. In this way, the full right to health, and the respect for the free development of personality are guaranteed, which were constitutionally established in the country. [Domínguez CM, Ramírez SV, Arrivillaga-Quintero M. Access to Health Services for Transgender Women in the City of Cali, Colombia. MedUNAB 2017-2018; 20(3): 296-309].&nbsp;&nbsp;Introducción: La población transgénero enfrenta retos en cuanto a la garantía del derecho a la salud y el acceso efectivo a los servicios de salud en todos los países. Objetivo: Describir y analizar el acceso a los servicios de salud preventivos, curativos, de atención específica, y asociados al gasto de bolsillo, en mujeres transgénero de Cali, Colombia. Metodología: Estudio observacional de tipo transversal con muestreo probabilístico. Se aplicó una adaptación de la Encuesta de Acceso a Servicios de Salud para Hogares Colombianos a un total de 109 personas que se auto identificaron como transgénero, mayores de 18 años. Se efectuó un análisis univariado de la totalidad de las variables evaluadas. Resultados: Si bien el 71.6% de las mujeres transgénero encuestadas se encontraban cubiertas por el sistema de salud, esto no garantiza el acceso oportuno a los servicios. Existe debilidad institucional por parte de las Entidades Promotoras de Salud (EPS) para promover servicios preventivos; el acceso a consulta con especialista y a medicamentos tuvo resultados desfavorables en oportunidad y calidad; no se atienden necesidades relacionadas con su identidad de género ni procesos de transformación corporal. Discusión: Tal como se ha reportado en otros estudios para población general, los hallazgos son coherentes con la estructura del sistema de salud colombiano que está diseñado para invertir los recursos en la atención de la enfermedad y no en la prevención. Conclusiones: Se requieren protocolos de atención diferencial dados los riesgos para personas transgénero por falta de atención médica y psicosocial. De esta manera, se garantiza el pleno derecho a la salud y el respeto por el libre desarrollo de la personalidad, establecido constitucionalmente en el país. [Domínguez CM, Ramírez SV, Arrivillaga-Quintero M. Acceso a servicios de salud en mujeres transgénero de la ciudad de Cali, Colombia. MedUNAB 2017-2018; 20(3): 296-309].&nbsp

Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies

Objective To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment.Design Systematic review and meta-analysis.Data sources Medline, Embase, PsycINFO, and LILACS to September 2016.Study selection Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine.Data extraction and synthesis Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis.Results There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment.Conclusions Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are potentially important, but further research must be conducted to properly account for potential confounding and selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in and out of each treatment.This work was partially supported by the ISCIII Network on Addictive Disorders (Networks for Cooperative Research in Health from the Carlos III Institute of Health) (grant No RD16/0017/0013 and RD12/0028/0018) and by the EMCDDA in the context of the activities related to identification, promotion, and monitor of best practices.S

Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs.

BACKGROUND: Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugsNeedle syringe programmes (NSP) and opioid substitution therapy (OST) are the primary interventions to reduce hepatitis C (HCV) transmission in people who inject drugs. There is good evidence for the effectiveness of NSP and OST in reducing injecting risk behaviour and increasing evidence for the effectiveness of OST and NSP in reducing HIV acquisition risk, but the evidence on the effectiveness of NSP and OST for preventing HCV acquisition is weak. OBJECTIVES: To assess the effects of needle syringe programmes and opioid substitution therapy, alone or in combination, for preventing acquisition of HCV in people who inject drugs. SEARCH METHODS: We searched the Cochrane Drug and Alcohol Register, CENTRAL, the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), MEDLINE, Embase, PsycINFO, Global Health, CINAHL, and the Web of Science up to 16 November 2015. We updated this search in March 2017, but we have not incorporated these results into the review yet. Where observational studies did not report any outcome measure, we asked authors to provide unpublished data. We searched publications of key international agencies and conference abstracts. We reviewed reference lists of all included articles and topic-related systematic reviews for eligible papers. SELECTION CRITERIA: We included prospective and retrospective cohort studies, cross-sectional surveys, case-control studies and randomised controlled trials that measured exposure to NSP and/or OST against no intervention or a reduced exposure and reported HCV incidence as an outcome in people who inject drugs. We defined interventions as current OST (within previous 6 months), lifetime use of OST and high NSP coverage (regular attendance at an NSP or all injections covered by a new needle/syringe) or low NSP coverage (irregular attendance at an NSP or less than 100% of injections covered by a new needle/syringe) compared with no intervention or reduced exposure. DATA COLLECTION AND ANALYSIS: We followed the standard Cochrane methodological procedures incorporating new methods for classifying risk of bias for observational studies. We described study methods against the following 'Risk of bias' domains: confounding, selection bias, measurement of interventions, departures from intervention, missing data, measurement of outcomes, selection of reported results; and we assigned a judgment (low, moderate, serious, critical, unclear) for each criterion. MAIN RESULTS: We identified 28 studies (21 published, 7 unpublished): 13 from North America, 5 from the UK, 4 from continental Europe, 5 from Australia and 1 from China, comprising 1817 incident HCV infections and 8806.95 person-years of follow-up. HCV incidence ranged from 0.09 cases to 42 cases per 100 person-years across the studies. We judged only two studies to be at moderate overall risk of bias, while 17 were at serious risk and 7 were at critical risk; for two unpublished datasets there was insufficient information to assess bias. As none of the intervention effects were generated from RCT evidence, we typically categorised quality as low. We found evidence that current OST reduces the risk of HCV acquisition by 50% (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.40 to 0.63, I(2) = 0%, 12 studies across all regions, N = 6361), but the quality of the evidence was low. The intervention effect remained significant in sensitivity analyses that excluded unpublished datasets and papers judged to be at critical risk of bias. We found evidence of differential impact by proportion of female participants in the sample, but not geographical region of study, the main drug used, or history of homelessness or imprisonment among study samples.Overall, we found very low-quality evidence that high NSP coverage did not reduce risk of HCV acquisition (RR 0.79, 95% CI 0.39 to 1.61) with high heterogeneity (I(2) = 77%) based on five studies from North America and Europe involving 3530 participants. After stratification by region, high NSP coverage in Europe was associated with a 76% reduction in HCV acquisition risk (RR 0.24, 95% CI 0.09 to 0.62) with less heterogeneity (I(2) =0%). We found low-quality evidence of the impact of combined high coverage of NSP and OST, from three studies involving 3241 participants, resulting in a 74% reduction in the risk of HCV acquisition (RR 0.26 95% CI 0.07 to 0.89). AUTHORS' CONCLUSIONS: OST is associated with a reduction in the risk of HCV acquisition, which is strengthened in studies that assess the combination of OST and NSP. There was greater heterogeneity between studies and weaker evidence for the impact of NSP on HCV acquisition. High NSP coverage was associated with a reduction in the risk of HCV acquisition in studies in Europe