Down-regulation of intra-hepatic T-cell signaling associated with GB virus C in a HCV/HIV co-infected group with reduced liver disease.

BACKGROUND & AIMS: Studies have shown that GB virus C (GBV-C) infection leads to reduced liver disease in hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection. Considering that the underlying mechanism(s) are unknown, we aim to identify differential gene and protein expression associated with GBV-C in HCV/HIV co-infection that may be responsible for reduced liver disease. METHODS: Liver, peripheral blood mononuclear cells (PBMCs), and plasma samples were collected from 43 HCV/HIV patients. Plasma was tested for GBV-C RNA by RT-PCR with NS5B gene primers. A microarray was performed on the liver and RT-qPCRs on the liver/PBMC samples. Hepatic protein expression was measured by immunohistochemistry. RESULTS: Sixteen out of 43 patients had GBV-C RNA. GBV-C was associated with reduced hepatic fibrosis (p=0.005) and inflammation (p=0.007). The microarray analysis of the liver samples (n=10) showed down-regulation of genes critical to intra-hepatic T-cell signaling associated with GBV-C. Quantitative RT-PCR of the liver samples (n=13) confirmed the down-regulation of lymphocyte-specific protein tyrosine kinase (LCK) (p=0.02) and docking protein 2 (DOK2) (p=0.04). No differences in the expression levels of these genes were observed in PBMCs (n=22) according to the GBV-C status. The hepatic expression of the LCK protein, measured by immunohistochemistry (n=36), was decreased in CD3-positive T-cells within portal tracts associated with GBV-C (p=0.003). This remained significant in multivariate analysis controlling for hepatic fibrosis and inflammation (p=0.027). No differences were observed in plasma cytokine concentrations (n=25) or ex-vivo peripheral T-cell responses (n=13) versus GBV-C status. CONCLUSIONS: GBV-C infection is associated with down-regulation of critical genes involved in intra-hepatic T-cell signaling in HCV/HIV co-infection. This may be relevant to the pathogenesis of reduced HCV-related liver disease in HIV co-infection.

Incidence of putative HIV superinfection and sexual practices among HIV-infected men who have sex with men.

OBJECTIVES: To determine the upper limit for the incidence of clinically important HIV superinfection among HIV-infected men who have sex with men (MSM) and its relationship with engagement in unsafe sexual practices. METHODS: This was a retrospective cohort and nested case-control study. Electronic files of all HIV-infected MSM not on antiretroviral therapy were reviewed. Those clients with sudden, unexplained and sustained declines in CD4 T-cell counts and increases in plasma HIV RNA were considered as being putatively superinfected with HIV and were recruited as cases, whereas those without these features were recruited as controls (four per case) to answer a self-administered questionnaire. RESULTS: Ten cases were identified from 145 eligible MSM (7%, 95% confidence interval 3-11%), comprising a rate of 3.6 per 100 person-years at risk. Cases had an annual decline in CD4 T-cell counts of 201 cells microL(-1) compared with 9 cells microL(-1) for controls. There were no statistically significant differences between cases and controls with regard to sexual practices that may have exposed them to acquisition of HIV superinfection (P-value >or= 0.4), nor in their perceptions or beliefs of HIV superinfection (P-value >or= 0.3). Only a minority reported no previous knowledge of HIV superinfection (17%, 5/30). Overall, both cases and controls were engaging frequently in unsafe sexual practices with casual partners who were HIV infected (80 and 52%, respectively; P-value=0.4) or whose HIV serostatus was unknown (40 and 50%, respectively; P-value=1.0). CONCLUSIONS: Despite considerable unsafe sexual practices occurring among this cohort of sexually active MSM the incidence of clinically significant HIV superinfection was likely to be less than 4% per year.

Reduction in hepatitis C-related liver disease associated with GB virus C in human immunodeficiency virus coinfection.

BACKGROUND & AIMS: It has been reported that GB virus C infection (GBV-C) leads to improved morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. However, GBV-C has no effect on the course of liver disease in hepatitis C virus (HCV) monoinfection. The aim of the study was to determine the influence of GBV-C infection on liver disease in patients with HCV/HIV coinfection. METHODS: Data on 158 HCV/HIV patients were collected from January 1996 to October 2005. Two plasma specimens, collected at least 18 months apart, were tested for GBV-C RNA by reverse transcription-polymerase chain reaction with primers to the NS5B gene and confirmed using E2 gene primers and sequencing. Antibodies to GBV-C E2 protein were also determined. Liver-related morbidity and mortality were assessed from patient records. RESULTS: Fifty-seven of 158 (36%) patients had GBV-C RNA and 94 (59%) had evidence of exposure to GBV-C based on combined polymerase chain reaction and antibody results. Thirty-four (21%) patients had features of cirrhosis, with 20 having compensated and 14 having decompensated cirrhosis. Active GBV-C RNA was significantly associated with a reduction in cirrhosis, both compensated and decompensated in multivariate analysis (hazard ratio, 0.27; 95% confidence interval, 0.08-0.88; P = .03), as well as in analysis for cirrhosis-free survival vs duration of HCV infection (P = .006). No significant effect on liver-related or overall survival was observed. CONCLUSIONS: In these HCV/HIV-coinfected patients, GBV-C RNA was associated with a significant reduction in the severity of HCV-related liver disease.

The evidence for a change in antenatal HIV screening policy in Australia.

Australia is one of the few developed countries without routine antenatal HIV screening, despite having the resources to undertake such a screening program and the availability of antiretroviral therapy. National policy recommends that only women with identified risk factors should be offered testing; however, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists recommends that all pregnant women be offered HIV testing as part of their antenatal care. Knowledge of a woman's HIV status during pregnancy allows interventions to improve her health and reduce the risk of transmission of HIV to her child. A universal antenatal HIV screening program meets many of the Wilson and Jungner criteria for population-based screening programs. This should be considered in the current review of Australia's HIV testing policy.

HIV and pregnancy in Australia.

It is estimated there are over 19 million women worldwide living with HIV infection. In Australia the total number of notified cases of HIV in women has been gradually increasing (the estimated number of women newly diagnosed with HIV infection was 78 in 2000 and 94 in 2001). Management of women in pregnancy and strategies to reduce perinatal transmission is critical, but differ significantly according to resource availability. The current review examines the best available scientific evidence and current guidelines for optimal management of HIV-infected women contemplating pregnancy in Australia.

The molecular epidemiology of HIV type 1 among Vietnamese Australian injecting drug users in Melbourne, Australia.

The proportion of human immunodeficiency virus type 1 (HIV-1) among Vietnamese injecting drug users (IDUs) in Melbourne, Australia exceeds that of the background population. To investigate the molecular epidemiology of HIV-1 among this group, the C2-V4 region of the HIV-1 envelope was directly sequenced from 11 Vietnamese Australians and 19 non-Vietnamese Australian controls. A significant difference in the distribution of the HIV-1 subtypes was demonstrated, with greater than 50% of Vietnamese Australian IDU shown to be infected with CRF01_AE-the predominant subtype in Southeast Asia, rather than subtype B, which dominates the Australian epidemic and which was found in 89.5% of the non-Vietnamese controls. The genetic diversity of the CRF01_AE epidemic in Vietnamese Australian IDUs was substantially lower that that of the background subtype B, consistent with a more recent introduction of a limited number of viral strains from Vietnam. These results support public health policy targeting Australian IDUs of Vietnamese ethnicity as a distinct vulnerable population.

HIV, ethnicity and travel: HIV infection in Vietnamese Australians associated with injecting drug use.

BACKGROUND: The movement of people with their constructed identities including ethnicity has always been one of the determinants of the human immunodeficiency virus (HIV) pandemic. An example of the contributions of travel and ethnicity to experiences of HIV can be seen in the Vietnamese community in Australia. OBJECTIVES: This paper seeks to describe the contributions of ethnicity and travel to the Australian HIV epidemic with particular reference to the evolving epidemic within the Vietnamese Australian community. STUDY DESIGN: We reviewed the available data on the HIV epidemic in Australia with reference to overseas acquisition, ethnicity, the epidemic in the Vietnamese community and the determinants of the current patterns of transmission within this community. RESULTS: Available data suggests that 20-25% of HIV infections notified in Australia are acquired overseas. This proportion is higher in some specific categories such as heterosexually acquired infections. Notification rates are no higher in Vietnamese Australians than in the general Australian population apart from infections associated with injecting drug use (IDU) notified in the state of Victoria. The reasons for this increased rate of notification include increased vulnerability to blood borne virus infection in Australia and the additional, unique risk of frequent travel to Vietnam, a country where IDU carries a high risk of HIV infection. CONCLUSIONS: Australia has succeeded in stabilising the HIV epidemic partly through successful interventions to limit the spread of infection among IDUs. There is now early evidence that HIV transmission may be increasing amongst Vietnamese Australian IDUs. Timely responses that help Vietnamese Australian IDUs reduce their accumulation of risk are likely to be important in determining the level of harm associated with IDU throughout Australia.

beta-Herpesvirus (human cytomegalovirus and human herpesvirus 6) reactivation in at-risk lung transplant recipients and in human immunodeficiency virus-infected patients.

Human herpesvirus (HHV)-6 is a beta-herpesvirus-like human cytomegalovirus (HCMV) with the potential to reactivate in immunocompromised persons. HHV-6 and HCMV were assessed in the peripheral blood leukocytes of 26 lung transplant recipients and of 37 human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy, to determine the degree of concordance between HHV-6 and HCMV reactivation in different biologic settings. In the lung transplant recipients (145 samples), HHV-6 was not detected, even though 44 (30%) of 145 samples were from 9 HCMV DNA-positive patients (13 episodes of HCMV pneumonitis). Among the HIV-infected patients (172 samples), HCMV DNA was detected in 29 (17%) of 172 samples from 10 patients (4 episodes of HCMV disease). HHV-6 DNA was detected in 2 HIV-infected patients who did not have HCMV detected at that time. These findings suggest that the pathobiologic control mechanisms for these 2 beta-herpesviruses may be significantly different.