HIV treatment outcomes among people who inject drugs in Victoria, Australia.

BACKGROUND: People who inject drugs (PWID) are a key population affected by HIV. We assessed the effectiveness of HIV treatment among a clinical cohort of people living with HIV (PLHIV) diagnosed and referred for community-based antiretroviral therapy (ART) in Victoria, Australia. METHODS: HIV notification data from a central statewide registry were matched with HIV clinical data from two large HIV treatment centers in Melbourne. We used survival analysis and Cox proportional hazard models to estimate time to AIDS and death for PWID in HIV treatment, compared with non-injectors, in the period 1996-2008. RESULTS: Of the 871 individuals, 93 (10.8%) had injecting as an exposure category and 671 (86%) had ever commenced ART. Adjusted analysis showed younger age, high initial CD4 cell count (>500 cells/mm(3)) or ever having a CD4 cell count >500/mm(3), and more recent calendar year of ART commencement were all associated with reduced hazards for AIDS and death, while older age, low initial CD4 cell count (<200/mm(3)), ever having a CD4 count <200/mm(3) (before or during treatment) and high initial viral load (>5 log10) were associated with increased risk of AIDS and death. PWID were no more likely to experience AIDS (HR 0.98 [0.54-1.80]) or death (HR 0.78 [0.18-3.42]) than non-injectors. CONCLUSION: Survival of HIV-infected PWID on HIV treatment was equivalent to non-injectors. CD4 cell count, initial viral load, calendar year of commencing ART and age are more important determinants of AIDS and mortality than injecting status for in-treatment PLHIV in Victoria, Australia.

HIV replication is associated with increased severity of liver biopsy changes in HIV-HBV and HIV-HCV co-infection.

Histological parameters were assessed in liver biopsies (n = 48) performed in patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and/or hepatitis C virus (HCV) in order to evaluate factors which were associated with significant liver disease. Necroinflammation and fibrosis was scored by the Ishak classification system, and binary logistic regression analysis was used to assess HIV and antiretroviral-related determinants of necroinflammation and fibrosis. A total of 46 biopsies were included; 33 were from HIV-positive patients co-infected with HCV and 15 biopsies were from HIV-positive patients co-infected with HBV. One HIV-positive patient was co-infected with HBV and HCV. Median biopsy inflammatory grade for the cohort was 8.5 (IQR 6-10), the median fibrosis Stage 2 (IQR 1.8-4), and the median steatosis score was 1 (IQR 0-2). At the univariate level, HIV-related variables that were significantly associated with more severe biopsy changes were higher HIV RNA at the time of biopsy (associated with inflammatory Grade 10+; P = 0.018) and any exposure to didanasine (ddI) or stavudine (D4T; associated with fibrosis Stage 3+; P = 0.022). HIV RNA at the time of biopsy remained significant at the multivariate level. Patients with HIV hepatitis co-infection in this cohort had surprisingly mild changes in liver histology, and there were no statistically significant differences between biopsy results in HBV compared to HCV co-infection. The association between HIV RNA and necroinflammation supports current recommendations for earlier initiation of HAART in patients with HIV-hepatitis co-infection.

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.

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.

Testing rates for sexually transmitted infections among HIV-infected men who have sex with men attending two different HIV services.

This study compares the testing rates of bacterial sexually transmitted infections (STIs) among HIV-positive men who have sex with men (MSM) attending two HIV clinics in Melbourne. Data on STI testing over a 12-month period were obtained for all HIV-positive MSM who attended the clinics between January and March 2006. Screening rates for bacterial STIs were significantly higher at a sexual health clinic (n = 254) compared with an infectious diseases clinic (n = 351), whether this was measured according to: at least one STI test being performed for chlamydia, gonorrhoea or syphilis (69% vs. 38%, P < 0.01); serological testing for syphilis alone (67% vs. 34%, P < 0.01); or 'complete' STI screening for pharyngeal gonorrhoea, urethral chlamydia, anal gonorrhoea, anal chlamydia and syphilis (41% vs. 6%, P < 0.01). Substantial differences in STI testing rates among HIV-positive MSM may exist between HIV clinical services depending on the measures in place that promote STI screening.

Reduction in hospitalwide incidence of infection or colonization with methicillin-resistant Staphylococcus aureus with use of antimicrobial hand-hygiene gel and statistical process control charts.

OBJECTIVE: To evaluate the impact of serial interventions on the incidence of methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: Longitudinal observational study before and after interventions. SETTING: The Alfred Hospital is a 350-bed tertiary referral hospital with a 35-bed intensive care unit (ICU). INTERVENTIONS: A series of interventions including the introduction of an antimicrobial hand-hygiene gel to the intensive care unit and a hospitalwide MRSA surveillance feedback program that used statistical process control charts but not active surveillance cultures. METHODS: Serial interventions were introduced between January 2003 and May 2006. The incidence and rates of new patients colonized or infected with MRSA and episodes of MRSA bacteremia in the intensive care unit and hospitalwide were compared between the preintervention and intervention periods. Segmented regression analysis was used to calculate the percentage reduction in new patients with MRSA and in episodes of MRSA bacteremia hospitalwide in the intervention period. RESULTS: The rate of new patients with MRSA in the ICU was 6.7 cases per 100 patient admissions in the intervention period, compared with 9.3 cases per 100 patient admissions in the preintervention period (P=.047). The hospitalwide rate of new patients with MRSA was 1.7 cases per 100 patient admissions in the intervention period, compared with 3.0 cases per 100 patient admissions in the preintervention period (P<.001). By use of segmented regression analysis, the maximum and conservative estimates for percentage reduction in the rate of new patients with MRSA were 79.5% and 42.0%, respectively, and the maximum and conservative estimates for percentage reduction in the rate of episodes of MRSA bacteremia were 87.4% and 39.0%, respectively. CONCLUSION: A sustained reduction in the number of new patients with MRSA colonization or infection has been demonstrated using minimal resources and a limited number of interventions.

HIV infection and high-density lipoprotein: the effect of the disease vs the effect of treatment.

HIV infection is commonly associated with hypoalphalipoproteinemia. It is not clear how much the HIV infection and/or treatment contribute to the changes in high-density lipoprotein (HDL) levels. Blood lipids of HIV-positive males were assessed in a retrospective study. The following groups of patients were studied: (1) untreated for at least 6 months; (2) treatment with highly active antiretroviral therapy (HAART) without protease inhibitor (PI); (3) treatment with a HAART regimen that includes a PI (HAART/PI); (4) treatment with HAART that includes low-dose ritonavir and a PI (HAART/PI/boost). Lipoprotein levels were compared with those of age-matched HIV-negative healthy subjects. Compared with the control group, HDL-cholesterol (HDL-C) levels were 22%, 11%, 14%, and 11% lower for currently untreated HIV, HAART, HAART/PI, and HAART/PI/boost groups, respectively. Negative correlations were found among HDL-C level, peak and current viral load, and duration of the disease and the treatment. A positive correlation was found between HDL-C and current and nadir CD4 cell count and CD4 percentage. When patients were divided into subgroups based on duration of antiretroviral therapy, patients treated with HAART and HAART/PI for 3 to 6 years were significantly less likely to have high HDL-C levels compared with the control group and patients treated for 1 to 3 years. A 5-fold decrease in the proportion of subjects with high HDL-C and a 3-fold increase in those with low HDL-C were found in the group treated with HAART/PI/boost. These data suggest that hypoalphalipoproteinemia in patients with HIV is likely to be secondary to HIV infection itself.

The prevalence and risk behaviours associated with the transmission of blood-borne viruses among ethnic-Vietnamese injecting drug users.

OBJECTIVE: To measure the prevalence and determinants of blood-borne virus (BBV) transmission in ethnic Vietnamese injecting drug users (IDUs). METHODS: The study was conducted in Melbourne, Australia, in 2003. It was a cross-sectional design with participants recruited from street-based illicit drug markets predominately using a snowball technique. One hundred and twenty-seven participants completed a questionnaire that asked about illicit drug use and participants' blood samples were tested for HIV, HCV and HBV. RESULTS: One hundred and three (81.1%) ethnic Vietnamese IDU study participants were HCV positive and three (2.4%) were HIV positive. More than 60% had evidence of being infected with HBV (either in the past, acute infection or chronic infection). Almost 60% had injected daily over the past 12 months. Fifty-nine participants had recently travelled to Vietnam; 24 (41%) had injected drugs in Vietnam; and three (12.5%) reported sharing injecting equipment in Vietnam. CONCLUSION: The prevalence of BBVs was higher in this study's IDU population compared with IDUs in Australia generally, despite the fact that the injecting risk behaviours were similar to IDUs more generally. IMPLICATIONS: Culturally sensitive drug treatment and education programs need to be developed in Australia for both ethnic Vietnamese IDUs and their families to reduce this group's risk of contracting a BBV.

A study to investigate the impact of the initiation of highly active antiretroviral therapy on the hepatitis C virus viral load in HIV/HCV-coinfected patients.

Changes in the hepatitis C virus (HCV) viral load (VL) were assessed in a retrospective study of 50 HIV/HCV-coinfected patients who initiated highly active antiretroviral therapy (HAART). Most patients responded to HAART [during the first 6 months, plasma HIV VL fell by a mean 1.39 log10, becoming undetectable (<400 copies/ml) in 22% and CD4+ T cells increased by a mean of 100 cells/microl], but surprisingly, 27 (54%) showed some rise and 25 (50%) showed a significant increase in the HCV VL. This figure was considered to be a minimum estimate. A majority of the patients showed an increase of less than 1 log10 that was associated with a rapid decrease in the HIV VL, whereas an increase in the HCV VL of greater than 1 log10, noted in eight patients, was associated with a baseline CD4+ cell count of less than 200 cells/microl. The increase in the HCV VL was not associated with hepatitis as determined by raised alanine transferase.

Skeletal myopathy associated with nucleoside reverse transcriptase inhibitor therapy: potential benefit of coenzyme Q10 therapy.

Zidovudine (ZDV) has been associated with 'ragged-red' fibre myopathy, due to its effects on myocyte mitochondria. Usually this is reversible with cessation of ZDV. We report a 52-year-old man, who in 1985 developed ragged-red fibre myopathy 14 years after diagnosis of HIV infection while on effective ZDV-based combination antiretroviral therapy (ART). He was treated with the mitochondrial anti-oxidant coenzyme Q10 and made an excellent recovery, without change of ARTs. This suggests a novel therapy for further investigation targeted at ZDV induced myopathy, potentially allowing continuation of antiviral treatments including ZDV.

Prevalence and characterization of lamivudine-resistant hepatitis B virus mutations in HIV-HBV co-infected individuals.

OBJECTIVE: To determine the prevalence of hepatitis B virus (HBV) genotypic resistance to lamivudine, identify risk factors associated with lamivudine resistance, and characterize the pattern of HBV polymerase mutations in patients co-infected with HIV. DESIGN: Retrospective cross-sectional study. METHODS: Thirty-three chronic HBV-infected patients were identified from a cohort of 1719 HIV-infected individuals. Patient information was collected from case records, HBV DNA was measured on stored serum by polymerase chain reaction, and positive samples underwent sequencing of HBV polymerase, basal core promoter and precore regions. RESULTS: Three groups of patients were identified: group 1 were viraemic in the absence of lamivudine-resistance mutations, group 2 were viraemic in association with lamivudine-resistance mutations, and group 3 were not viraemic. Group 2 patients with lamivudine-resistant mutations had significantly higher HBV-DNA viral loads but did not differ in duration of lamivudine therapy, HBV genotype, HIV viral load or CD4 cell count compared with patients with wild-type HBV. Group 2 individuals also demonstrated significantly higher serum alanine aminotransferase (ALT) levels than group 1, who were higher than group 3. Unique mutations were detected in HBV polymerase, including rtV173L plus rtL180M plus rtM204V, which occurred in three patients. This virus has the in-vitro characteristics of a 'vaccine escape' mutant of HBV. CONCLUSION: Genotypic HBV lamivudine resistance was found in 39% of HIV-HBV co-infected individuals treated with lamivudine as part of highly active antiretroviral therapy. These patients exhibited significantly elevated HBV viral loads and serum ALT, and three were infected with a lamivudine-resistant HBV strain that was potentially transmissible to HBV-vaccinated individuals.

Immune reconstitution hepatitis in HIV and hepatitis B coinfection, despite lamivudine therapy as part of HAART.

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection occurs commonly. The introduction of antiretroviral therapy can result in immune reconstitution hepatitis. We describe 2 coinfected patients who developed clinical flares of HBV disease, despite the inclusion of lamivudine, a drug with anti-HBV activity, in their HAART regimens. Potential strategies to manage individuals with HBV/HIV coinfection are discussed.

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.

Novel mutations in the thymidine kinase and DNA polymerase genes of acyclovir and foscarnet resistant herpes simplex viruses infecting an immunocompromised patient.

BACKGROUND: Mutations in the thymidine kinase (TK) and DNA polymerase (pol) genes of herpes simplex virus (HSV) may confer resistance to antiviral drugs, particularly in the context of immunosuppression induced by infection with the human immunodeficiency virus (HIV). OBJECTIVES: To characterise the HSV type 2 (HSV-2) TK and DNA pol genes in an immunocompromised patient with clinical resistance to both acyclovir and foscarnet. STUDY DESIGN: The TK and DNA pol genes of isolates obtained over a 2-year period from an AIDS patient with severe genital herpes infection were characterised both phenotypically and genotypically. RESULTS: HSV strains that were acyclovir resistant/foscarnet sensitive, acyclovir sensitive/foscarnet sensitive and acyclovir resistant/foscarnet resistant were isolated during this time. The TK gene of all the acyclovir resistant isolates contained a large 969 bp deletion which extended into a downstream untranslated region. The foscarnet resistance was associated with an S725G mutation in a conserved region (region II) of the herpesvirus DNA pol gene. CONCLUSIONS: Clinical and virological suppression of the infection was not always associated with subsequent reactivation with wild-type virus. Mutations of the nature we describe have not previously been reported occurring simultaneously in HSV strains isolated from patients treated with acyclovir and foscarnet.

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.

Analysis of HIV-1 viral load in seminal plasma samples.

BACKGROUND: With HIV-1-infected individuals now facing the prospect of relatively long and healthy lives, many discordant couples (where the male is HIV-1 seropositive) are seeking to have children. To assist reducing the risks of heterosexual and subsequent vertical transmission in this situation, quantification of HIV-1 viral load in seminal plasma may be effective as one of several measures to reduce the risk of infecting the mother during insemination, potentially providing a better indication of infectivity than blood plasma analysis. OBJECTIVE(S): To modify existing molecular methods for the purpose of analysing HIV-1 viral load in seminal plasma. METHODS: Two commercial assays for HIV-1 RNA quantification were used to assess their sensitivity, specificity and precision for quantification of seminal plasma samples. Seminal plasma samples were prepared with an additional centrifugation step to aid removal of inhibitors to molecular assays. RESULTS: Seminal plasma samples exhibited specificity of >95%, equivalent to that reported by the manufacturers of the commercial assays. With additional centrifugation, complete inhibition of 2/19 (10%) seminal plasma samples was observed using the RT-PCR assay, and inhibition was not apparent in the bDNA assay. Quantification of HIV-1 RNA in seminal plasma samples in both assays was equivalent to that observed in plasma samples and did not appear to be affected by the additional centrifugation step. CONCLUSION: Minor modification of the RT-PCR assay procedure by additional centrifugation of seminal plasma improved the sensitivity of the assay. Inhibition was not apparent with the bDNA assay.

C-reactive protein as a predictor of cardiovascular risk in HIV-infected individuals.

UNLABELLED: Background In some studies HIV infection confers approximately two-fold higher risk of cardiac events compared with the general population. C-reactive protein (CRP) is a well-characterised biomarker of cardiac events in the general population and is also elevated in patients with HIV infection. The aim of this study was to determine the predictive value of CRP for cardiac events in HIV-infected individuals. METHODS: We retrospectively analysed CRP levels in stored plasma samples from HIV-infected patients who did or did not experience a coronary event in a case-controlled manner. All CRP measurements were performed using a high-sensitivity assay (hs-CRP). RESULTS: Of the study participants with samples available, we found slightly elevated hs-CRP levels in the cardiac cases (median 3.5, IQR 1.6-14.4, n=23) compared with controls (median 2.6, IQR1.2-8.3, n=49) which were shown to not be statistically significant P=0.20. Analysis of CRP as a binary variable (≥5mgL(-1)) was also not statistically significant (OR: 1.32, 95% CI 0.48-3.63). CONCLUSIONS: CRP levels may indicate elevated risk of future cardiac events, however this must be interpreted with caution due to the generalised elevation of CRP during HIV infection. CRP has no predictive value for atherosclerosis, and further research is required to improve early prediction of cardiovascular disease in HIV infection.

High levels of psychological distress in MSM are independent of HIV status.

This study assessed psychological distress (PD) in men who have sex with men (MSM) accessing primary health clinics in Australia. Relationships between PD, HIV status and substance use were explored. A cross-sectional convenience sample of 250 MSM completed the Personality Assessment Screener (PAS). One-third (n = 83) scored in the PAS clinically significant range, suggesting significant mental health symptoms. Negative Affect (27 per cent clinically significant), Suicidal Thinking (29 per cent clinically significant) and Amphetamine use significantly positively correlated with PD. There were no significant differences between HIV diagnostic groups on PD. A third of MSM displayed PD. Psychological screening may provide valuable information for improving the psychological well-being of MSM, regardless of their HIV status.