Hepatitis C and HIV infections: implications for clinical care in injection drug users

Our objective is to provide a state-of-the-art review on hepatitis C (HCV) and the human immunodeficiency virus (HIV) in injection drug users (IDUs), highlighting important clinical issues. We performed a literature review from the MEDLINE database for research from 1966 to 2003, with an emphasis on recent consensus documents. Of the estimated 15 million illicit drug users in the U.S., approximately 1.0 to 1.5 million inject drugs. IDUs are at significant risk of contracting HCV and HIV, with IDUs accounting for 60% of new HCV cases and 25% of new HIV infections. It is a major risk factor for HCV/HIV coinfection, which significantly impacts on each disorder's progression. It appears that treatment response in IDUs with HCV or HIV is similar to non-IDUs with these viruses and that medication adherence and treatment outcomes are optimized when linked with substance abuse treatment. Providers caring for patients who are or were IDUs must be aware of the management of these diseases and make efforts to integrate their medical care with the treatment of their substance abuse.     

Management of hepatitis C virus in special populations: patient and treatment considerations.

The most common chronic blood-borne infection in the United States is caused by hepatitis C virus. An estimated 3.9 million people (1.8%) in the United States have been infected with the hepatitis C virus, excluding certain subpopulations who are at high risk for hepatitis C virus infection. Among these subpopulations are an estimated 255,000 (15%) of prison inmates and 175,000 (22%) of homeless people. Prevalence of hepatitis C virus infection is also high among veterans (6.6% overall and even higher among homeless veterans). The single most important risk factor for hepatitis C virus infection is injection drug use; up to 90% of illicit injection drug users are infected with hepatitis C virus. This review describes the prevalence of hepatitis C virus in special populations and discusses the treatment options for patients with severe disease, transplant recipients, and patients at high risk for infection. Close monitoring and management of therapeutic side effects are required to assist these patients in adhering to therapy.     

Epidemiology of hepatitis C virus infection

Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century. Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.     

Hepatitis C virus infection in United States correctional institutions

In the United States, over 6 million people are under correctional supervision and over 2 million are in custody and receiving health care. Prisoners are overrepresented by individuals with high risk for hepatitis C virus (HCV) infection, including injection drug users, the sexual partners of injection drug users, and people living with HIV or AIDS and mental illness. As such, it is estimated that approximately 30% of all prisoners are infected with HCV. Despite this high prevalence, little has been done to implement effective therapy for treating this potentially curable infection in this setting. Correctional settings, with their structured environment and managed care approach, are ideal settings to screen, evaluate, and provide treatment and promote risk reduction interventions that will contribute to society’s improved public health.     

High-income countries see increase in epidemic. Italy sees increase in sexual transmission

The HIV/AIDS epidemic has grown to include about 1.6 million people who live in high-income countries, including the estimated 76,000 people who became infected with the virus in 2002.     

The influence of hiv coinfection on the natural history of hcv infection

In the United States, it is estimated that more than 4 million people are infected with the hepatitis C virus (HCV) and over 1.25 million are infected with HIV. With common routes of transmission, approximately 30% of HIV-infected individuals are coinfected with HCV. Deaths due to opportunistic infections from HIV declined with the advent of highly active antiretroviral therapy, whereas manifestations of end-stage liver disease have become more apparent with the increased longevity. Current efforts are directed toward understanding whether HIV/HCV coinfection affects the natural history of each virus. Early outcomes in treating coinfected patients for their HCV were below expectations, whereas recent treatment trials with highly selected patients and newer therapeutic agents have shown greater success. The aim of this paper is to review the epidemiology, natural history, and treatment outcomes, as well as unique challenges in the management of HIV/HCVcoinfected patients.     

HCV In At Risk Populations: Who Can be Treated and How?

Hepatitis C virus (HCV), a major cause of chronic liver disease, affects an estimated 5 million people in the Unites States [1] and close to 170 million people worldwide. Certain subpopulations including injection drug users, prison inmates, the homeless, ethnic minorities, American veterans, and HIV co-infected patients are considered high risk for viral acquisition and are disproportionately affected by HCV. This review describes the prevalence of HCV in these at-risk populations including those with cirrhosis, chronic kidney disease (CKD), solid organ transplantation and presents current treatment options.     

India has the largest number of people infected with HIV

With a population of almost 1 billion people and an estimated 4 million people infected with HIV, India is thought to be the country with the largest number of HIV-infected people in the world. According to UNAIDS, HIV is firmly embedded in India's general population and rapidly spreading into rural areas previously thought to be relatively spared from the epidemic. Almost 500,000 people are infected in Tamil Nadu and the infection rate is 3 times higher in villages than in cities. According to the National AIDS Control Organization, the rate of HIV infection among attendees of STD clinics in Mumbai increased from 23% to 36% in 1 year, and 51% of prostitutes in Mumbai and 55.8% of IV drug users in Manipur are infected. It is estimated that AIDS will cost India US$11 billion cumulatively by 2000, 5% of the country's gross domestic product. Negotiations are underway for the World Bank to loan India $200 million with which to combat HIV/AIDS. Since antiretroviral therapy is too expensive for most Indians, vaccine research must be accelerated in India. HIV infection in India is mainly of HIV-1 subtype C, although subtypes A and B, along with some new recombinant subtypes, have also been reported. HIV-2 has been reported sporadically.     

Treatment of chronic hepatitis B virus infection in resource‐constrained settings: expert panel consensus

Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource‐constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV‐related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20–30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV‐infected persons in Africa who are co‐infected with HBV. Progressive liver disease has been shown to occur in co‐infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV‐infected persons should be screened for HBV infection; HIV/HBV co‐infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource‐constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource‐constrained settings.     

Aiming for the elimination of viral hepatitis in Australia,New Zealand,and the Pacific Islands and Territories: Where are we now and barriers to meeting World Health Organization targets by 2030

Viral hepatitis affects more than 320 million people globally, leading to significant morbidity and mortality due to liver failure and hepatocellular carcinoma (HCC). More than 248 million people (3.2% globally) are chronically infected with hepatitis B virus (HBV), and an estimated 80 million people (1.1% globally) are chronically infected with hepatitis C virus (HCV). In 2015, more than 700 000 deaths were directly attributable to HBV, and nearly 500 000 deaths were attributable to HCV infection; 2–5% of HBV‐infected people develop HCC per annum irrespective of the presence of cirrhosis, whereas 1–5% HCV‐infected people with advanced fibrosis develop HCC per annum. The rapidly escalating global mortality related to HBV and HCV related viral hepatitis to be the 7th leading cause of death worldwide in 2013, from 10th leading cause in 1990. Australia, New Zealand, and Pacific Island Countries and Territories fall within the World Health Organization Western Pacific Region, which has a high prevalence of viral hepatitis and related morbidity, particularly HBV. Remarkably, in this region, HBV‐related mortality is greater than for tuberculosis, HIV infection, and malaria combined. The region provides a unique contrast in viral hepatitis prevalence, health system resources, and approaches taken to achieve World Health Organization global elimination targets for HBV and HCV infection. This review highlights the latest evidence in viral hepatitis epidemiology and explores the health resources available to combat viral hepatitis, focusing on the major challenges and critical needs to achieve elimination in Australia, New Zealand, and Pacific Island Countries and Territories.     

Does substance use compromise depression treatment in persons with HIV? Findings from a randomized controlled trial†

Depression and substance use are significant obstacles to effective HIV care. Using data derived from a randomized controlled trial of persons with HIV who are homeless or marginally housed, this study assesses the utility of antidepressant treatment among persons with HIV, depression, and active substance use. Participants were diagnosed with depressive disorders and randomly assigned to receive directly observed therapy with fluoxetine or a referral to community mental health treatment. Assessments, conducted at baseline and every 3 months over a 9-month period, included the Hamilton Rating Scale for Depression, the Beck Depression Inventory II, and self-report of alcohol, crack, cocaine, heroin, or methamphetamine use in the past 90 days. To investigate the effect of antidepressant treatment in the setting of active substance use, the authors fit mixed-effects linear regression models to estimate the effect of directly observed fluoxetine on depressive symptom severity after stratifying by any alcohol use or any illicit drug use. To investigate whether alcohol use or illicit drug use moderated the antidepressant treatment response, the authors examined the interaction terms. The effect of directly observed fluoxetine treatment on depression symptom severity was statistically significant irrespective of alcohol use status. When stratified by illicit drug use status, the effect of directly observed fluoxetine treatment on depression symptom severity was statistically significant only among persons who did not use illicit drugs. The interaction terms were not statistically significant. This study found a benefit of antidepressant treatment in persons with HIV, depression, and alcohol use. In addition, this study found no evidence that either alcohol use or illicit drug use moderates the antidepressant treatment response. Altogether, these findings support the use of antidepressant medication in this population. The public health impact of research in this area is significant given the known adverse effects of depression on HIV-related health outcomes. ClinicalTrials.gov Identifier: NCT00338767.     

A new approach to prevent HIV transmission: Project Protect intervention for recently infected individuals

Past research suggests that as many as 50% of onward human immunodeficiency virus (HIV) transmissions occur during acute and recent HIV infection. It is clearly important to develop interventions which focus on this highly infectious stage of HIV infection to prevent further transmission in the risk networks of acutely and recently infected individuals. Project Protect tries to find recently and acutely infected individuals and prevents HIV transmission in their risk networks. Participants are recruited by community health outreach workers at community-based HIV testing sites and drug users' community venues, by coupon referrals and through referrals from AIDS clinics. When a network with acute/recent infection is identified, network members are interviewed about their risky behaviors, network information is collected, and blood is drawn for HIV testing. Participants are also educated and given prevention materials (condoms, syringes, educational materials); HIV-infected participants are referred to AIDS clinics and are assisted with access to care. Community alerts about elevated risk of HIV transmission are distributed within the risk networks of recently infected. Overall, 342 people were recruited to the project and screened for acute/recent HIV infection. Only six index cases of recent infection (2.3% of all people screened) were found through primary screening at voluntary counseling and testing (VCT) sites, but six cases of recent infection were found through contact tracing of these recently infected participants (7% of network members who came to the interview). Combining screening at VCT sites and contact tracing the number of recently infected people we located as compared to VCT screening alone. No adverse events were encountered. These first results provide evidence for the theory behind the intervention, i.e., in the risk networks of recently infected people there are other people with recent HIV infection and they can be successfully located without increasing stigma for project participants.     

The epidemiology of the human immunodeficiency virus

During the past decade, AIDS has become a global health problem with 182,000 cases reported from 152 countries. It is estimated that nearly five to ten million people are infected worldwide with the etiologic agent of AIDS, human immunodeficiency virus type 1 (HIV-1). With a mean incubation period from time of infection to the development of AIDS of eight to ten years, it is projected that nearly all HIV-1-infected individuals will develop AIDS within the next 15 years. In the United States alone, 104,210 cases of AIDS and more than 61,000 deaths have been reported. Sexual, parenteral, and perinatal transmission routes have remained the major modes of transmission, although the proportion of cases within each risk behavior category has changed. Recently, there has been a dramatic increase in the proportion of patients with AIDS who have acknowledged either IV drug use or heterosexual contact with other individuals at high risk for HIV infection. Inner-city minority populations are disproportionately represented among AIDS patients, and HIV-seroprevalence studies demonstrate significantly higher rates of infection among blacks and Hispanics compared with whites, even within the same risk category. In 1988, the US Public Health Service estimated that approximately 1.0 to 1.5 million Americans were currently infected with HIV-1 and that by the end of 1992, a cumulative total of 380,000 cases of AIDS will be diagnosed. In 1992, 80,000 cases of AIDS may be diagnosed, with 66,000 deaths occurring during that year alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

The HIV infection in Europe: large East-West disparity

In 2001, western Europe faces an endemic situation for AIDS (22.8 cases per million population) and for HIV infection (54.9 cases per million), the most affected groups remaining injecting drug users and the homo/bisexual men. However, numbers of new HIV diagnoses are increasing among persons infected through heterosexual contact. Central Europe have been relatively spared, with AIDS incidence under 6 cases per million per year, and new HIV diagnoses between 7 and 10 cases per million. On the other hand, eastern Europe shows an epidemic increase in the number of newly diagnosed HIV infections (233 cases in 1994, around 100,000 reported cases in 2001, ie 349 cases per million population) affecting all countries.     

Modelling the impact of antiretroviral therapy on the epidemic of HIV

Thirty years after HIV first appeared it has killed close to 30 million people but transmission continues unchecked. In 2009, an estimated 1.8 million lives were lost and 2.6 million more people were infected with HIV [1]. To cut transmission, many social, behavioural and biomedical interventions have been developed, tested and tried but have had little impact on the epidemic in most countries. One substantial success has been the development of combination antiretroviral therapy (ART) that reduces viral load and restores immune function. This raises the possibility of using ART not only to treat people but also to prevent new HIV infections. Here we consider the impact of ART on the transmission of HIV and show how it could help to control the epidemic. Much needs to be known and understood concerning the impact of early treatment with ART on the prognosis for individual patients and on transmission. We review the current literature on factors associated with modelling treatment for prevention and illustrate the potential impact using existing models. We focus on generalized epidemics in sub- Saharan Africa, with an emphasis on South Africa, where transmission is mainly heterosexual and which account for an estimated 17% of all people living with HIV. We also make reference to epidemics among men who have sex with men and injection drug users where appropriate. We discuss ways in which using treatment as prevention can be taken forward knowing that this can only be the beginning of what must become an inclusive dialogue among all of those concerned to stop acquired immune deficiency syndrome (AIDS).     

The Relationship Between HIV Infection and Cardiovascular Disease

Over 30 million people are currently living with human immunodeficiency virus (HIV) infection, and over 2 million new infections occur per year. HIV has been found to directly affect vascular biology resulting in an increased risk of cardiovascular disease compared to uninfected persons. Although HIV infection can now be treated effectively with combination antiretroviral medications, significant toxicities such as hyperlipidemia, diabetes, and excess cardiovascular co-morbidity; as well as the potential for significant drug-drug interactions between HIV and cardiovascular medications, present new challenges for the management of persons infected with HIV. We first review basic principles of HIV pathogenesis and treatment and then discuss relevant clinical management strategies that will be useful for cardiologists who might be involved in the care of HIV infected patients.Key Words: HIV, cardiology, treatment, natural history, review.     

Human immunodeficiency virus (HIV) in developing countries

The human immunodeficiency virus (HIV) is causing the most destructive epidemic of recent times, having been responsible for the deaths of more than 25 million people since it was first recognised in 1981. This global epidemic remains out of control, with reported figures for 2005 of 40 million people infected with HIV. During 2005 there were 4.9 million new infections, showing that transmission is not being prevented, and there were 3.1 million deaths from the acquired immunodeficiency syndrome (AIDS), reflecting the lack of a definitive cure and the limited access to suppressive antiretroviral treatment in the developing countries that are most severely affected. The current state of the epidemic and the response to date are here reviewed. Present and future opportunities for prevention, treatment and surveillance are discussed, with particular reference to progress towards an HIV vaccine, the expansion of the provision of highly active antiretroviral therapy, and the need to focus control programmes on HIV as an infectious disease, rather than as a development issue.     

Hepatitis C infection among drug users in northern Thailand

Illicit drug users are commonly infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). We evaluated the prevalence, incidence, and risk behaviors associated with HCV infection in 1,859 drug users in northern Thailand. The HCV prevalence was 27.3%: 86.0% among drug injectors (IDUs) and 5.3% among those who did not inject. Sexual behavior was not significantly associated with HCV among IDUs or drug users who used but didn't inject illicit drugs; only injection behaviors were independently associated with HCV in multivariate analysis. Among men, a history and increasing frequency of injecting drugs, older age, and a history of incarceration were associated with HCV infection. Among 514 opiate users who were HCV and HIV seronegative at baseline, 41 incident HCV infections and 6 HIV infections occurred on follow-up; the HCV incidence was 5.43/100 person-years; it was 44.3/100 person-years in IDUs and 1.9/100 person-years in non-injectors. HCV and HIV among drug users in Thailand are common and primarily associated with injection behavior.     

1998年艾滋病状况和主要工作

截止1998年底,全国31省、自治区、直辖市共报告艾滋病病毒感染者12639例.其中艾滋病病人417例,死亡224例.经三种传播途径的感染均有发现,但主要经血—注射毒品感染.据估计,我国实际艾滋病病毒感染者可能已逾40万.1998年全国共报告艾滋病病毒感染者3306例.感染途径仍以静脉注射毒品为主,占75.2%;20个省、自治区、直辖市报告在吸毒人群中发现了艾滋病病毒感染者,以新疆和广西的疫情发展最快.新疆1998年报告数首次超过云南,居第一位.1998年,一半以上吸毒人群哨点发现了艾滋病病毒感染者,其感染率明显高于1997年;感染的性乱人群哨点数增加;局部高发地区,已发现孕妇感染,说明艾滋病病毒正从高危人群向一般人群扩散.指出了1998年全国艾滋病疫情报告和监测工作的不足点;总结了国家1998年艾滋病防治的主要工作及制订的艾滋病防治的主要文件、方针和策略.     

Mechanism(s) Involved in Opioid Drug Abuse Modulation of HAND

Drug abuse and HIV infection are interlinked. From the onset of the HIV/AIDS epidemic, the impact of illicit drug use on HIV disease progression has been a focus of many investigations. Both laboratory-based and epidemiological studies strongly indicate that drug abuse may exacerbate HIV disease progression and increase mortality and morbidity in these patients. Increase susceptibility to opportunistic infection has been implicated as one of the major causes for this detriment. Furthermore, opioids are known to elicit prevalence of neurodegenerative disorders in HIV-infected patients. Numerous authors have delineated various molecular as well as cellular mechanisms associated with neurological complications in these patients. This review gives an overview of these findings. Understanding the mechanisms will allow for the development of targeted therapies aimed at reducing the progression of neurocognitive decline in the drug abusing HIV infected individuals.