HIV and HCV: from Co-infection to epidemiology, transmission, pathogenesis, and treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immunodeficiency syndrome (AIDS), a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide, resulting in a serious public health burden. Due to shared routes of transmission, co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease, particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial, most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely, HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications, co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review, we focus on the epidemiology and transmission of HIV and HCV, the impact of the two viruses on each other, and their treatment.      

HIV and tuberculosis in India

The global impact of the converging dual epidemics of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major public health challenges of our time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common opportunistic infection in HIV-infected patients as well as the leading cause of death. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. The diagnosis of TB is based on sputum smear microscopy, a 100-year old technique and chest radiography, which has problems of specificity. Extra-pulmonary, disseminated and sputum smear negative manifestations are more common in patients with advanced immunosuppression. Newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-poor settings. Treatment of HIV-TB co-infection is complex and associated with high pill burden, overlapping drug toxicities, risk of immune reconstitution inflammatory syndrome (IRIS) and challenges related to adherence. From a programmatic point of view, screening of all HIV-infected persons for tuberculosis and vice-versa will help identify co-infected patients who require treatment for both infections. This requires good coordination and communication between the TB and AIDS control programs, in India.     

The challenges of modelling antibody repertoire dynamics in HIV infection

Antibody affinity maturation by somatic hypermutation of B-cell immunoglobulin variable region genes has been studied for decades in various model systems using well-defined antigens. While much is known about the molecular details of the process, our understanding of the selective forces that generate affinity maturation are less well developed, particularly in the case of a co-evolving pathogen such as HIV. Despite this gap in understanding, high-throughput antibody sequence data are increasingly being collected to investigate the evolutionary trajectories of antibody lineages in HIV-infected individuals. Here, we review what is known in controlled experimental systems about the mechanisms underlying antibody selection and compare this to the observed temporal patterns of antibody evolution in HIV infection. We describe how our current understanding of antibody selection mechanisms leaves questions about antibody dynamics in HIV infection unanswered. Without a mechanistic understanding of antibody selection in the context of a co-evolving viral population, modelling and analysis of antibody sequences in HIV-infected individuals will be limited in their interpretation and predictive ability.     

HIV and HCV： from Co-infection to Epidemiology, Transmission, Pathogenesis, and Treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immu-nodeficiency syndrome (AIDS),a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission,co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease,particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely,HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications,co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review,we focus on the epidemiology and transmission of HIV and HCV,the impact of the two viruses on each other,and their treatment.     

Prion diseases of humans and farm animals: epidemiology, genetics, and pathogenesis

Neuronal vacuolation (spongiosis), neuronal death, and pronounced glial reactions are the hallmarks of transmissible spongiform encephalopathies (TSEs), or prion diseases. A wealth of physical, biochemical, and immunological evidence indicates that the TSE agent, termed prion, does not contain agent-specific nucleic acid encoding its own constituents, as is the case for all other infectious pathogens. Also, no adaptive immune responses are elicited upon infection. A defining feature of TSEs is the deposition, mainly in the brain and lymphoreticular tissues, of an aggregated and structurally abnormal protein, designated PrP(Sc) or PrP-res, which represents a conformational isomer of the ubiquitous surface protein PrP(C). Biochemical and genetic evidence link PrP and its gene to the disease. Although TSEs are by definition transmissible, a growing number of Prnp-associated non-infectious neurodegenerative proteinopathies are now being recognized.     

Hepatitis C in India

Hepatitis C is an emerging infection in India and an important pathogen causing liver disease in India. The high risk of chronicity of this blood-borne infection and its association with hepatocellular carcinoma underscores its public health importance. Blood transfusion and unsafe therapeutic interventions by infected needles are two preventable modalities of spread of hepatitis C infection. In addition, risk factor modification by reducing the number of intravenous drug users will help curtail the prevalence of this infection. This review summarizes the extent, nature and implications of this relatively new pathogen in causing disease in India.     

Current status of immunology research in India

Rudimentary studies on aspects of biochemistry in India date back to 1927. But, in the field of Immunology, such studies were started by scholars only during early 1970s at the All India Institute of Medical Sciences, New Delhi, India. Science and Technology was not an immediate priority until 1961 due to domestic and political conditions in the country. We were then 11 years old since independence and our focus was on economic and social developments. Gradually, improvements were made in the field and now we have 15 to 20 major groups (small in size) of immunologists in the country, who have made significant contribution in the field during the last 8 to 10 years. Hence, we anticipate improvements in manpower and infrastructure in the near future.     

Epidemiology of sudden cardiac death in rural South India - insights from the andhra pradesh rural health initiative

Background

Sudden cardiac death (SCD) is a common initial presentation of coronary artery disease (CAD). Despite the growing epidemic of CAD in India, the epidemiology of SCD is largely unknown.

Objective

The objective of the study was to define the prevalence and determinants of sudden cardiac deaths in rural South India.

Methods

Prospective mortality surveillance was conducted in 45 villages (180,162 subjects) in rural South India between January 2006 and October 2007. Trained multipurpose health workers sought to do verbal autopsies within 4 weeks of any death. Detailed questionnaires including comorbidities and circumstances surrounding death were recorded. SCD was adjudicated using the modified Hinkle-Thaler classification.

Results

A total of 1916 deaths occurred in the study population over the 22 month time period and verbal autopsy was obtained in 1827 (95%) subjects. Overall mean age of the deceased was 62 ± 20 years and 1007 (55%) were men. Cardiovascular and cerebrovascular diseases together accounted for 559 deaths (31%), followed by infectious disease (163 deaths, 9%), cancer (126 deaths, 7%) and suicide (93 deaths, 5%).Of the 1827 deaths, after excluding accidental deaths (89 deaths), 309 deaths (17%) met criteria for SCD. Cardiovascular disease was the underlying causes in the majority of the SCD events (231/309 (75%)). On multivariate analyses, previous MI/CAD (p < 0.001, OR 14.25), hypertension (p < 0.001, OR 1.84), and age groups between 40-60 yrs (p=0.029) were significantly associated with SCD.

Conclusion

Sudden cardiac death accounted for up to half of the cardiovascular deaths in rural Southern India. Traditional cardiovascular risk factors were strongly associated with SCD.     

Snapshot of HIV pathogenesis in China

Several reviews have focused on the nature of HIV infection and its spread in various geographical regions of China. In contrast, this review provides a comprehensive update on the prevalence of multiple HIV- 1 subtypes, consequent emergence of recombinant and novel forms of HIV- 1 in China, and the implications this may have on HIV diversity and the development of effective vaccines. In addition it also examines the dissemination of primary drug resistance in therapy naive patients, as well as co-infections with two other important viruses-hepatitis B and C. The main purpose of this review is to provide a current snapshot of HIV-1 pathogenesis in China and possibly shed some light on the future of HIV evolution, and potential challenges for future vaccine and anti-retroviral therapeutics against HIV strains in this area.     

Snapshot of HIV pathogenesis in China

INTRODUCTION A recent report by the National Intelligence Council es- timates that by 2010 five countries, India, China, Nigeria, Ethiopia and Russia, cumulatively, will harbor the largest number of individuals infected with the Human Immuno- deficiency V…     

Snapshot of HIV pathogenesis in China

Several reviews have focused on the nature of HIV infection and its spread in various geographical regions of China.In contrast, this review provides a comprehensive update on the prevalence of multiple HIV-1 subtypes, consequent emergence of recombinant and novel forms of HIV-1 in China, and the implications this may have on HIV diversity and the development of effective vaccines. In addition it also examines the dissemination of primary drug resistance in therapy na(i)ve patients, as well as co-infections with two other important viruses-hepatitis B and C. The main purpose of this review is to provide a current snapshot of HIV-1 pathogenesis in China and possibly shed some light on the future of HIV evolution, and potential challenges for future vaccine and anti-retroviral therapeutics against HIV strains in this area.     

Analysis of prevalence, risk factors and molecular epidemiology of Clostridium difficile infection in Kuwait over a 3-year period

We conducted a prospective study to evaluate the prevalence and epidemiology of CDI in Kuwait government hospitals over a 3-year period, January 2003 to December 2005, to determine the ribotypes responsible for CDI and to estimate the prevalence of ribotype 027. We also conducted a case-control study to identify the risk factors in our patient population. A total of 697 stool samples from patients with suspected CDI were obtained and sent to Anaerobe Reference Laboratory, Faculty of Medicine, Kuwait University for Clostridium difficile toxin detection, culture and PCR ribotyping. During the period, 73 (10.5%) out of 697 patients met the case definition of CDI. Of these, 56 (76.7%) were hospital-acquired and 17 (23.3%) were from outpatient clinics. Thus, the prevalence of hospital-acquired CDI amongst patients with diarrhoea was 8% over the study period; the prevalence in 2003, 2004 and 2005 was 9.7%, 7.8% and 7.2%, respectively. Our data showed that 42.9% of the CDI patients were above 60 years, of which >79% were aged 71 years and above. Patients with CDI were more likely than the controls to have been exposed to immunosuppressive drugs and feeding via nasogastric tube. The most common ribotypes isolated during this study were 002, 001, 126 and 140 and they represent 55.1% of all isolates. PCR ribotype 027 was not isolated.     

Governmental policies on HIV infection in China

This article is a general review of the evolvement of HIV/AIDS-related public policies in China since 1980＇s. It tracks the important laws, regulations and other governmental documents in regard to HIV/AIDS prevention mainly at central level.     

Epidemiology of HIV infection and AIDS in Croatia--an overview

This article presents an overview of HIV/AIDS epidemiology and surveillance in Croatia 20 years after the first documented case of AIDS in the country. Here we describe strategies employed for HIV/AIDS surveillance in Croatia as well as preliminary results of HIV seroprevalence among most-at-risk populations (MARPs) research conducted by the Infectious Diseases Epidemiology Service at the Croatian National Institute of Public Health (CNIPH). Croatia has a low incidence and prevalence of HIV and AIDS. At the end of 2005, there were 553 documented cases of HIV infection, 239 of which progressed to AIDS. In Croatia, AIDS is being registered within MARPs only and dominantly among men who have sex with men (MSM). AIDS patients and HIV infected persons are found in all parts of the country. Crude prevalence of HIV among MARPs was found to be 0.9%. It is necessary to continue with current prevention and control measures in the country, and to create a culture of awareness and precaution, a strategy that has proven effective in reducing risk of HIV infection.     

Governmental policies on HIV infection in China

This article is a general review of the evolvement of HIV/AIDS-related public policies in China since 1980‘s. It tracks the important laws, regulations and other governmental documents in regard to HIV/AIDS prevention mainly at central level.     

肝移植患者真菌感染的流行病学特点及耐药性分析

目的了解肝移植术后真菌感染的种类及耐药特性,为临床治疗提供依据。方法分析2003年6月至2006年6月,我院67例肝移植患者术后感染的标本,鉴定真菌种类,分析其耐药性。结果67例肝移植患者有21例发生真菌感染,占肝移植患者的31.3%;共检出73株真菌,以酵母菌感染为主,占98.6%,其中近平滑念珠菌、白色念珠菌、热带念珠菌、季也蒙念珠菌、克柔念珠菌的检出率分别是53.4%、21.9%、9.6%、8.2%、2.7%。曲霉菌感染1例。药敏试验显示73株真菌对两性霉素B(AMB)、5-氟胞嘧啶(5-FC)、制霉菌素(MYS)、酮康唑(KTC)、益康唑(ECO)和咪康唑(MIC)的平均敏感率分别为98.6%、95.7%、87.1%、70.0%、65.7%和64.3%。结论加强肝移植术后真菌的鉴定和耐药性监测,对指导临床治疗具有重要意义。     

The expanding HIV-1 epidemic aggravates therapeutics and vaccine development programs in India

Human Immunodeficiency Virus Type 1 (HIV-1) displays extensive genetic diversity globally that poses a serious challenge in designing suitable therapeutic measures for protective immune responses in the host. After the first detection of AIDS cases in 1986, India now has the third largest HIV epidemic in world. The HIV-1 epidemic in India is still growing with introduction of new strains/subtypes and this creates a serious problem for the clinician and basic science researchers to find the effective measures. Neighboring countries in the North and North-eastern regions play an important role in the HIV-1 pandemic. An extensive multinational collaborative research effort is needed in order to identify the risk groups and geographic locales is required to monitor HIV-1 spread in Asia and to produce a successful preventive program.