Infection with HIV and hepatitis C virus among injecting drug users in a prevention setting: retrospective cohort study

Objectives: To estimate the incidence of HIV and hepatitis C virus and risk factors for seroconversion among a cohort of injecting drug users. Design: Retrospective cohort study. Setting: Primary healthcare facility in central Sydney. Subjects: Injecting drug users tested for HIV-1 antibody (n=1179) and antibodies to hepatitis C virus (n=1078) from February 1992 to October 1995. Main outcome measures: Incidence of HIV-1 and hepatitis C virus among seronegative subjects who injected drugs and underwent repeat testing. Demographic and behavioural risk factors for hepatitis seroconversion. Results: Incidence of HIV-1 among 426 initially seronegative injecting drug users was 0.17/100 person years (two seroconversions) compared with an incidence of hepatitis C virus of 20.9/100 person years (31 seroconversions) among 152 injecting drug users initially negative for hepatitis C virus. Incidence of hepatitis C virus among injecting drug users aged less than 20 years was 75.6/100 person years. Independent risk factors for hepatitis C virus seroconversion were age less than 20 years and a history of imprisonment. Conclusions: In a setting where prevention measures have contributed to the maintenance of low prevalence and incidence of HIV-1, transmission of hepatitis C virus continues at extremely high levels, particularly among young injecting drug users.

Key messages

• The prevalence and incidence of hepatitis C virus is high, while the prevalence and incidence of HIV remains low among injecting drug users
• Young age and history of imprisonment are risk factors for acquisition of hepatitis C virus infection
• HIV prevention strategies have been relatively ineffective in preventing hepatitis C virus infection in this population
• The role of imprisonment in the acquisition of hepatitis C infection should be further investigated

     

Occult hepatitis B virus infection among injecting drug users in the Central-West Region of Brazil

The prevalence of occult hepatitis B virus (HBV) infection was investigated in 149 hepatitis B surface antigen (HBsAg) negative injecting drug users (IDUs) in the Central-West Region of Brazil. Of these individuals, 19 were positive for HBV DNA, resulting in an occult HBV infection prevalence of 12.7% (19/149); six of these 19 individuals had anti-HBV core and/or anti-HBV surface antibodies and 13 were negative for HBV markers. All IDUs with occult hepatitis B reported sexual and/or parenteral risk behaviours. All HBV DNA-positive samples were successfully genotyped. Genotype D was the most common (17/19), followed by genotype A (2/19). These findings reveal a high prevalence of occult HBV infection and the predominance of genotype D among IDUs in Brazil''s Central-West Region.     

Characteristics of hepatitis C infection in injecting drug users in Zadar County, Croatia

The aim of the study was to determine additional risk factors that could increase the prevalence of hepatitis C (HCV) infection among injecting drug users (IDU). The study included 327 heroin addicts registered in Zadar County, Croatia. The participants were divided into two groups according to their HCV status. HCV-positive and HCV-negative study participants were compared. HCV-positive group started injecting heroin at earlier age (median 18.5 years) than HCV-negative group (median 20.0 years) (p = 0.032) and had been injecting heroin for a significantly longer period (median 5 years vs. median 4 years, respectively; p < 0.001). IDUs in HCV-positive group shared their injecting equipment significantly more often than IDUs in HCV-negative group (p < 0.001; chi2 = 32.7). The main reasons for starting drugs were curiosity, psychological reasons (depression and/or neurosis), and peer or partner pressure in HCV-positive group, and fun, curiosity, and peer pressure in HCV-negative group (p = 0.051; chi2 = 23.6). Earlier onset of heroin use, longer heroin use, sharing injection equipment, curiosity, and psychological problems as reasons for starting drugs were associated with higher prevalence of HCV infection among injecting heroin users in Zadar County.     

The explosive human immunodeficiency virus type 1 epidemic among injecting drug users of Kathmandu, Nepal, is caused by a subtype C virus of restricted genetic diversity

An explosive epidemic of human immunodeficiency virus type 1 (HIV-1) has been documented among the injecting drug user population of Kathmandu, Nepal, whose seropositivity rate has risen from 0 to 40% between 1995 and 1997. By using Catrimox to preserve whole-blood RNA at ambient temperature for transportation, HIV-1 envelope V3-V4 sequences were obtained from 36 patients in this group. Analysis of the sequences indicated a homogenous epidemic of subtype C virus, with at least two independent introductions of the virus into the population. Viral diversity was restricted within two transmission subclusters, with the majority of variation occurring in V4. Calculation of the synonymous-to-nonsynonymous mutation ratio (Ks:Ka) across this region showed that significant evolutionary pressure had been experienced during the rapid horizontal spread of the virus in this population, most strongly directed to the region between V3 and V4.     

HCV genotype analysis in HCV-HIV-co-infected Puerto Ricans who are injecting drug users: undetermined and mixed infections.

Direct percutaneous exposure is the main route of HCV transmission. In Puerto Rico half of people infected with HIV use illicit drugs. The effects of HCV in the course of HIV infection and vice versa have been extensively studied, but remain highly controversial. This may be due to HCV genetic heterogeneity. Therefore, a complex classification into genotypes has emerged that prompted us to determined how this impacts a population of intravenous drug users (IDUs) co-infected with HIV-1. Using Inno-LiPa II technique, we analyzed samples from 171 HCV-HIV-1-co-infected IDUs and 375 from a general HCV population of unknown HIV or source of infection status. Similar HCV genotype distribution was detected in these populations. HCV genotype 1a was the most frequently in IDUs-co-infected with HIV-1, followed by 1b and 3a. Twenty mixed infections and 5 undetermined genotypes were reported. A reduced HCV viral load was observed in HIV-1 positives with wasting syndrome. Individuals with a high HIV-1 viral load presented a low HCV viral load. There were no correlation between HCV genotypes and AIDS-related event. Patients with genotype 1b showed a higher HCV viral load. Males presented higher HCV viral load than females. Females were predominantly affected by genotype 1a, and men by 1a and 1b. Neither the HCV viral load nor the frequency of genotypes were influenced by the antiretroviral modality. The importance of continuous genotype monitoring is stressed.     

中国国内首次发现Ⅰ基因型乙型肝炎病毒基因序列

对云南省参加健康体检人员中一份乙肝表面抗原阳性标本S区基因序列测定,以了解其分子生物学特点。利用巢式PCR扩增HBV S基因片段,并对扩增产物进行序列测定,将基因序列提交到GenBank上进行BLAST搜索,同时运用Mega软件进行同源性分析,并构建基因树,并将其核苷酸和氨基酸与已报道的A~I基因型参考株的同源性进行比较。核苷酸和氨基酸比较结果证明,此标本病毒基因型为HBV I基因型。本文所发现的I基因型标本为国内首次报道。     

High seroprevalence of toxoplasma gondii and HIV-1 co-infection among drug users in Yunnan province,southwest China

正Dear Editor,Toxoplasma gondii was discovered more than 100 years ago and has a broad-spectrum of intermediate hosts in addition to its definitive host,felids.Although it does not cause symptomatic illness in most adults,it can lead to mental retardation in congenitally infected children and serious     

A time since onset of injection model for hepatitis C spread amongst injecting drug users

Studies of hepatitis C virus (HCV) infection amongst injecting drug users (IDUs) have suggested that this population can be separated into two risk groups (naive and experienced) with different injecting risk behaviours. Understanding the differences between these two groups and how they interact could lead to a better allocation of prevention measures designed to reduce the burden of HCV in this population. In this paper we develop a deterministic, compartmental mathematical model for the spread of HCV in an IDU population that has been separated into two groups (naive and experienced) by time since onset of injection. We will first describe the model. After deriving the system of governing equations, we will examine the basic reproductive number $R_0$ , the existence and uniqueness of equilibrium solutions and the global stability of the disease free equilibrium (DFE) solution. The model behaviour is determined by the basic reproductive number, with $R_0=1$ a critical threshold for endemic HCV prevalence. We will show that when $R_0\le 1$ , and HCV is initially present in the population, the system will tend towards the globally asymptotically stable DFE where HCV has been eliminated from the population. We also show that when $R_0>1$ there exists a unique non-zero equilibrium solution. Then we estimate the value of $R_0$ from epidemiological data for Glasgow and verify our theoretical results using simulations with realistic parameter values. The numerical results suggest that if $R_0>1$ and the disease is initially present then the system will tend to the unique endemic equilibrium.     

Patterns of childhood trauma and psychological distress among injecting heroin users in China

Background

Childhood trauma has been reported as a possible cause of future substance abuse in some countries. This study reports the prevalence of childhood trauma and examines its association with psychological distress among injecting drug users from mainland China.

Methodology

The study was conducted in three government-operated drug rehabilitation facilities in Shanghai, China in 2007. The Early Trauma Inventory Self Report-Short Form (ETISR-SF) was used to evaluate 4 types (general, emotional, physical and sexual) and severity of childhood trauma, and the Symptom Checklist-90-Revised (SCL-90-R) to evaluate psychological distress.

Principal Findings

Among 341 injecting drug users who completed the study, about 80% reported one or more types of childhood trauma, specifically 53% general trauma, 56% physical abuse, 36% emotional abuse and 26% sexual abuse. Compared to female injecting drug users, males reported significantly higher scores of general trauma and physical abuse, but lower sexual abuse scores. Hierarchical linear regression analyses showed that greater physical and emotional abuse in childhood predict greater current psychopathological distress among these injecting drug users in China.

Conclusions

The results reveal a high prevalence of childhood trauma among injecting drug users in China, and it is comparable to other similar studies in Western countries. It is important to consider the role of childhood trauma in the prevention and treatment of substance abuse.     

Risk factors for human T cell lymphotropic virus type I among injecting drug users in northeast Brazil: possibly greater efficiency of male to female transmission

It was observed in the city of Salvador, State of Bahia, the highest seroprevalence of human T cell lymphotropic virus type 1 (HTLV-I) infection in Brazil as demonstrated by national wide blood bank surveys. In this paper, we report results of an investigation of drug use and sexual behavior associated with HTLV-I infection among male and female injecting drug users (IDUs) in Salvador. A cross sectional study was conducted in the Historical District of Salvador from 1994-1996 (Projeto Brasil-Salvador) and 216 asymptomatic IDUs were selected using the snowball contact technique. Blood samples were collected for serological assays. Sera were screened for human immunodeficiency virus (HIV-1/2) and HTLV-I/II antibodies by ELISA and confirmed by Western blot. The overall prevalence of HTLV-I/II was 35.2% (76/216). The seroprevalence of HTLV-I, HTLV-II and HIV-I was for males 22%, 11.3% and 44.1% and for females 46.2%, 10.3% and 74.4% respectively. HTLV-I was identified in 72.4% of HTLV positive IDUs. Variables which were significantly associated with HTLV-I infection among males included needle sharing practices, duration of injecting drug use, HIV-I seropositivity and syphilis. Among women, duration of injecting drug use and syphilis were strongly associated with HTLV-I infection. Multivariate analysis did not change the direction of these associations. Sexual intercourse might play a more important role in HTLV-I infection among women than in men.     

The prevalence of human immunodeficiency virus type 1 and hepatitis C virus among injection drug users who use high risk inner-city locales in Miami, Florida

In order to estimate the prevalence of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) co-infection in hard-to-reach intravenous drug users, 199 subjects from high-risk inner-city locales, the so called "shooting galleries", were consented, interviewed, and tested in Miami, FL, US. Positive HIV-1 status was based on repeatedly reactive ELISA and confirmatory Western Blot. Positive HCV status was based on reactive ELISA and confirmatory polymerase chain reaction techniques. Overall, 50 (25%) were not infected with either virus, 61 (31%) were HIV-1/HCV co-infected, 17 (8%) infected by HIV-1 only, and 71 (36%) infected by HCV only. The results of the multivariable analyses showed that more years using heroin was the only significant risk factor for HCV only infection (odds ratio = 1.15; 95% confidence interval = 1.07, 1.24) and for HIV-1/HCV co-infection (odds ratio = 1.17; 95% confidence interval = 1.09, 1.26). This paper demonstrates that HIV-1/HCV co-infection is highly prevalent among so called "shooting galleries".     

Prevalence and genotypes of GB virus C/hepatitis G virus among blood donors in Central Brazil

A survey was conducted in a blood donor population of Central Brazil aiming to investigate the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) infection and also to analyze the virus genotypes distribution. A total of 241 voluntary blood donors were interviewed at the State Blood Bank in Goiania, State of Goiás, Brazil. Blood samples were collected and serum samples tested for GBV-C/HGV RNA by polymerase chain reaction. Genotypes were determined by restriction fragment length polymorphism (RFLP) analysis. Seventeen samples were GBV-C/HGV RNA-positive, resulting in a prevalence of 7.1% (95% CI: 4.2-11.1). A significant trend of GBV-C/HGV RNA positivity in relation to age was observed, with the highest prevalence in donors between 29-39 years old. Ten infected individuals were characterized by reporting parenteral (30%), sexual (18%), both (6%) and intrafamiliar (6%) transmission. However, 7 (40%) GBV-C/HGV RNA-positive donors did not mention any potential transmission route. RFLP analysis revealed the presence of genotypes 1 and 2 of GBV-C/HGV; more precisely, 10 (58.9%) samples were found belonging to the 2b subtype, 4 (23.5%) to the 2a subtype, and 3 (17.6%) to genotype 1. The present data indicate an intermediate endemicity of GBV-C/HGV infection among this blood donor population, and a predominant circulation of genotype 2 (subtype 2b) in Central Brazil.     

Development of a GB virus B marmoset model and its validation with a novel series of hepatitis C virus NS3 protease inhibitors

GB virus B (GBV-B), a flavivirus closely related to HCV, has previously been shown to infect and replicate to high titers in tamarins (Saguinus sp.). This study describes the use of GBV-B infection and replication in the common marmoset (Callithrix jacchus) for the successful development and validation of a surrogate animal model for hepatitis C virus (HCV). Infection of marmosets with GBV-B produced a viremia that peaked at 10(8) to 10(9) genome copies/ml for a period of 40 to 60 days followed by viral clearance at 60 to 80 days postinfection. Passage of the initial tamarin-derived GBV-B in marmosets produced an infectious stock that gave a more reproducible and consistent infection in the marmoset. Titration of the virus stocks in vivo indicated that they contained 1 infectious unit for every 1,000 genome copies. Cultures of primary marmoset hepatocytes were also successfully infected with GBV-B, with high levels of virus detected in supernatants and cells for up to 14 days postinfection. Treatment of GBV-B-infected hepatocyte cultures with a novel class of HCV protease inhibitor (pyrrolidine 5,5 trans-lactams) reduced viral levels by more than 2 logs. Treatment of GBV-B-infected marmosets with one such inhibitor resulted in a 3-log drop in serum viral titer over 4 days of therapy. These studies provide the first demonstration of the in vivo efficacy of a small-molecule inhibitor for HCV in an animal model and illustrate the utility of GBV-B as a surrogate animal model system for HCV.     

Replication and infectivity of a novel genotype 1b hepatitis C virus clone

Hepatitis C virus infection is a major public health problem because of an estimated 170 million carriers worldwide. Genotype 1b is the major subtype of HCV in many countries and is resistant to interferon therapy. Study of the viral life cycle is important for understanding the mechanisms of interferon resistance of genotype 1b HCV strains. For such studies, genotype 1b HCV strains that can replicate and produce infectious virus particles in cultured cells are required. In the present study, we isolated HCV cDNA, which we named the NC1 strain, from a patient with acute severe hepatitis. Subgenomic replicon experiments revealed that several mutations enhanced the colony-formation efficiency of the NC1 replicon. The full-length NC1 genome with these adaptive mutations could replicate in cultured cells and produce infectious virus particles. The density gradient profile and morphology of the secreted virus particles were similar to those reported for the JFH-1 virus. Further introduction of a combination of mutations of the NS3 and NS5a regions into the NC1 mutants further enhanced secreted core protein levels and infectious virus titers in the culture medium of HCV-RNA-transfected cells. However, the virus infection efficiency was not sufficient for autonomous virus propagation in cultured cells. In conclusion, we established a novel cell culture-adapted genotype 1b HCV strain, termed NC1, which can produce infectious virus when the viral RNA is transfected into cells. This system provides an important opportunity for studying the life cycle of the genotype 1b HCV.     

国家公园类型划分与空间识别——以云南省为例

国家公园是我国推进生态文明建设的重大制度创新,如何科学地对国家公园进行类型划分及空间识别,是国家公园布局和建设中的基础性工作,既有必要性也有紧迫性。本研究以中国国情为基础,参考国际经验,将国家公园划分为荒野导向型、生态优先型、游憩导向型与遗产导向型,构建了一个比较完整的国家公园分类体系。并以自然和人文多样化程度较高的云南为案例,以“双评价”为基础建立了一套指标体系和区划规则,利用人工神经网络建立土地利用演化学习算法,利用融入自适应惯性机制的元胞自动机展开时空模拟,对云南全域进行高分辨率不同类型国家公园的空间辨识,并通过收缩-膨胀原理对识别区域进行比较、修正和优化,进而提出未来云南国家公园布局的综合方案。结果表明: 云南省国家公园主要集中在三江地区与横断山区、滇西以及西南部地区,这3类地区可作为未来国家公园区划与分类保护的重点。本研究所建立的国家公园类型划分和空间识别的一般性可推广的研究范式和工作流程可作为全国应用的参考。     

Recombination in hepatitis C virus: identification of four novel naturally occurring inter-subtype recombinants

Recombination in Hepatitis C virus (HCV) is considered to be rare. In this study, we performed a phylogenetic analysis of 1278 full-length HCV genome sequences to identify potential recombination events. Nine inter-genotype recombinants were identified, all of which have been previously reported. This confirms the rarity of inter-genotype HCV recombinants. The analysis also identified five inter-subtype recombinants, four of which are documented for the first time (EU246930, EU246931, EU246932, and EU246937). Specifically, the latter represent four different novel recombination types (6a/6o, 6e/6o, 6e/6h, and 6n/6o), and this was well supported by seven independent methods embedded in RDP. The breakpoints of the four novel HCV recombinants are located within the NS5B coding region and were different from all previously reported breakpoints. While the locations of the breakpoints identified by RDP were not identical, they are very close. Our study suggests that while recombination in HCV is rare, this warrants further investigation.     

Anti-nef antibodies and other predictors of disease progression in HIV-1 seropositive injecting drug users.

A cross-sectional and retrospective longitudinal study has been conducted in three Italian infectious disease centres to evaluate the role of anti-nef antibodies and other markers (HIV-1 p24 antigen, p24 Ag; Beta 2-microglobulin, B2-M; and number of CD4+ lymphocytes) as predictors of disease progression in HIV seropositive injecting drug users (IDUs). The selected patients were: 1) HIV-seropositive IDUs in different stages of HIV infection; 2) HIV-seropositive IDUs who had developed AIDS, from whom serial serum samples were available during the asymptomatic stage, and 3) HIV seropositive IDUs who remained asymptomatic through a follow-up period of the same duration as the patients who developed AIDS. Absence of anti-nef antibodies was associated with symptomatic HIV infection. A significant association between the absence of anti-nef antibodies, the presence of p24 Ag, high levels of B2-M, a number of CD4+ lymphocytes less than 500/ml at first visit and disease progression was found. Subjects who were persistently positive for antibody to nef were less likely to develop AIDS than those who were transiently or persistently negative. This difference was statistically significant (p = 0.03). The results of this study show that absence or disappearance of anti-nef antibodies may be used as predictor of disease evolution in HIV seropositive IDUs. This study also confirms the usefulness of other markers, such as p24 Ag, B2-M and number of CD4+ lymphocytes previously shown to be predictive of rapid disease progression for predicting the course of HIV seropositive IDUs.