Ten-year mortality trends among persons diagnosed with HIV infection in England and Wales in the era of antiretroviral therapy: AIDS remains a silent killer.

OBJECTIVES: We present national trends in death rates and the proportion of deaths attributable to AIDS in the era of effective antiretroviral therapy (ART), and examine risk factors associated with an AIDS-related death. METHODS: Analyses of the national HIV-infected cohort for England and Wales linked to death records from the Office of National Statistics were performed. Annual all-cause mortality rates were calculated by age group and sex for the years 1999-2008 and rates for 2008 were compared with death rates in the general population. Risk factors associated with an AIDS-related death were investigated using a case-control study design. RESULTS: The all-cause mortality rate among persons diagnosed with HIV infection aged 15-59 years fell over the decade: from 217 per 10 000 in 1999 to 82 per 10 000 in 2008, with declines in all age groups and exposure categories except women aged 50-59 years and persons who inject drugs (rate fluctuations in both of these groups were probably a result of small numbers). Compared with the general population (15 per 10 000 in 2008), death rates among persons diagnosed with HIV infection remained high, especially in younger persons (aged 15-29 years) and persons who inject drugs (13 and 20 times higher, respectively). AIDS-related deaths accounted for 43% of all deaths over the decade (24% in 2008). Late diagnosis (CD4 count < 350 cells/µL) was the most important predictor of dying of AIDS [odds ratio (OR) 10.55; 95% confidence interval (CI) 8.22-13.54]. Sixty per cent of all-cause mortality and 81% of all AIDS-related deaths were attributable to late diagnosis. CONCLUSIONS: Despite substantial declines, death rates among persons diagnosed with HIV infection continue to exceed those of the general population in the ART era. Earlier diagnosis could have prevented 1600 AIDS-related deaths over the decade. These findings highlight the need to intensify efforts to offer and recommend an HIV test in a wider range of clinical and community settings.

Low and decreasing vaccine effectiveness against influenza A(H3) in 2011/12 among vaccination target groups in Europe: results from the I-MOVE multicentre case-control study.

Within the Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) project we conducted a multicentre case­control study in eight European Union (EU) Member States to estimate the 2011/12 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza A(H3) among the vaccination target groups. Practitioners systematically selected ILI / acute respiratory infection patients to swab within seven days of symptom onset. We restricted the study population to those meeting the EU ILI case definition and compared influenza A(H3) positive to influenza laboratory-negative patients. We used logistic regression with study site as fixed effect and calculated adjusted influenza vaccine effectiveness (IVE), controlling for potential confounders (age group, sex, month of symptom onset, chronic diseases and related hospitalisations, number of practitioner visits in the previous year). Adjusted IVE was 25% (95% confidence intervals (CI): -6 to 47) among all ages (n=1,014), 63% (95% CI: 26 to 82) in adults aged between 15 and 59 years and 15% (95% CI: -33 to 46) among those aged 60 years and above. Adjusted IVE was 38% (95%CI: -8 to 65) in the early influenza season (up to week 6 of 2012) and -1% (95% CI: -60 to 37) in the late phase. The results suggested a low adjusted IVE in 2011/12. The lower IVE in the late season could be due to virus changes through the season or waning immunity. Virological surveillance should be enhanced to quantify change over time and understand its relation with duration of immunological protection. Seasonal influenza vaccines should be improved to achieve acceptable levels of protection.

Influenza-related deaths--available methods for estimating numbers and detecting patterns for seasonal and pandemic influenza in Europe.

Two methodologies are used for describing and estimating influenza-related mortality: Individual-based methods, which use death certification and laboratory diagnosis and predominately determine patterns and risk factors for mortality, and population-based methods, which use statistical and modelling techniques to estimate numbers of premature deaths. The total numbers of deaths generated from the two methods cannot be compared. The former are prone to underestimation, especially when identifying influenza-related deaths in older people. The latter are cruder and have to allow for confounding factors, notably other seasonal infections and climate effects. There is no routine system estimating overall European influenza-related premature mortality, apart from a pilot system EuroMOMO. It is not possible at present to estimate the overall influenza mortality due to the 2009 influenza pandemic in Europe, and the totals based on individual deaths are a minimum estimate. However, the pattern of mortality differed considerably between the 2009 pandemic in Europe and the interpandemic period 1970 to 2008, with pandemic deaths in 2009 occurring in younger and healthier persons. Common methods should be agreed to estimate influenza-related mortality at national level in Europe, and individual surveillance should be instituted for influenza-related deaths in key groups such as pregnant women and children.

Oseltamivir-resistant influenza A(H1N1) viruses detected in Europe during season 2007-8 had epidemiologic and clinical characteristics similar to co-circulating susceptible A(H1N1) viruses.

During the 2007-08 influenza season, high levels of oseltamivir resistance were detected among influenza A(H1N1) viruses ina number of European countries. We used surveillance data to describe influenza A(H1N1) cases for whom antiviral resistance testing was performed. We pooled data from national studies to identify possible risk factors for infection with a resistant virus and to ascertain whether such infections led to influenza illness of different severity. Information on demographic and clinical variables was obtained from patients or their physicians. Odds ratios for infection with an oseltamivir resistant virus and relative risks for developing certain clinical outcomes were computed and adjusted through multivariable analysis. Overall, 727 (24.3%) of 2,992 tested influenza A(H1N1) viruses from 22 of 30 European countries were oseltamivir-resistant. Levels of resistance ranged from 1% in Italy to 67% in Norway. Five countries provided detailed case-based data on 373 oseltamivir resistant and 796 susceptible cases. By multivariable analysis, none of the analysed factors was significantly associated with an increased risk of infection with anoseltamivir-resistant virus. Similarly, infection with an oseltamivir-resistant virus was not significantly associated with a different risk of pneumonia, hospitalisation or any clinical complication. The large-scale emergence of oseltamivir-resistant viruses in Europe calls for a review of guidelines for influenza treatment.

Pandemic influenza A(H1N1) 2009 vaccines in the European Union.

Pandemic vaccines from four manufacturers are now available for use within the European Union (EU). Use of these vaccines will protect individuals and reduce the impact on health services to more manageable levels. The majority of the severely ill will be from known risk groups and the best strategy will be to start vaccinating in line with the recommendation from the European Union Health Security Committee prioritizing adults and children with chronic conditions, pregnant women and healthcare workers. The composition of authorized vaccines is reviewed in this article. The vaccine strain in all authorized pandemic vaccines worldwide is based on the same initial isolate of influenza A/California/7/2009 (H1N1)v but the vaccines differ in conditions for virus propagation, antigen preparation, antigen content and whether they are adjuvanted or not. The vaccines are likely to be effective since no significant genetic or antigenic drift has occurred and there are already mechanisms for estimating clinical effectiveness. Influenza vaccines have good safety records and no safety concerns have so far been encountered with any of the vaccines developed. However, special mechanisms have been devised for the early detection and rigorous investigation of possible significant side effects in Europe through post-marketing surveillance and analysis. Delivery of the vaccines to the risk groups will pose difficulties where those with chronic illnesses are not readily identifiable to the healthcare services. There is considerable scope for European added value through Member States with excess vaccines making them available to other states.

[Kidney transplantation in Italy: an evolving scenario]. / Il trapianto di rene in Italia: una realtà in evoluzione.

BACKGROUND: Italian transplantation systems have dramatically improved in the last decade. Kidney transplantations are now strictly monitored and excellent results has been achieved in terms of quality and the ability to reduce waiting times for receiving transplantation. METHODS: The Italian organizational retrieval and transplant system is articulated on four levels: local, regional, inter-regional and national. The Italian Transplant Information System (SIT) was set up in 2000 in accordance with Law 91/99. Patient data on the waiting lists and follow-up of transplanted patients are routinely collected. RESULTS: A total of 4406 kidney transplants have been carried out in the 40 Italian kidney transplant centers in 2001-2003. The survival analysis was conducted for the 2000-2002 in 4222 cases. Overall 1-yr survival was 92.4% for the graft and 97% for the patients. After adjusting for variables independently associated with the outcome at multivariate analysis (for example, the case-mix), patient and graft survival at 1 yr was 98.1% and 93.8%, respectively. No remarkable differences in 1-yr graft survival were observed between the 40 Italian kidney transplant centers. At multivariate analysis, variables independently associated with graft failure were donor age, degree of HLA mismatch and recipient case-mix. Analysis of the waiting list showed approximately 6500 patients waiting for kidney transplantation. The mean waiting time was 3.04 yrs, with a mortality rate of 1.18% per year. CONCLUSIONS: Kidney transplantation activity in Italy has produced excellent results in terms of quality and number of transplants per year. However, the number of patients on the waiting list and the waiting time call for further action to increase the number of available organs.

Correlates of independent HIV-1 replication in the CNS and of its control by antiretrovirals.

OBJECTIVE: To investigate in detail factors associated with independent replication of HIV-1 in CNS, and to predict its therapeutic control. METHODS: HIV RNA concentration was measured by PCR in 134 cross-sectional paired plasma and CSF samples from 95 patients infected with HIV-1 with various conditions, and in longitudinal CSF samples from 50 patients on antiretroviral treatment. Monocyte chemotactic protein (MCP)-1 was quantified in CSF by ELISA. RESULTS: High HIV RNA levels either in plasma or in CSF did not correlate with HIV RNA concentration in the paired biologic sample. A high CSF-to-plasma HIV RNA ratio, suggesting independent viral replication in the CNS, was associated with higher CSF viral load and higher CSF MCP-1 levels. Higher MCP-1 levels in the CSF were also associated with neurologic disorders and were not influenced by the use of highly active antiretroviral therapy (HAART). A higher number of antiretroviral drugs with CSF penetration correlated with a more profound CSF HIV-1 load reduction, independently from the use of HAART alone. Virologic suppression in CSF was predicted by a higher number of CSF-penetrating antiretrovirals and by the baseline CSF viral load, whereas lower baseline CD4 counts and higher MCP-1 levels were associated with increased risk of virologic failure. CONCLUSIONS: Quantification of HIV RNA in CSF is clinically useful, particularly in patients with neurologic disorders. CSF penetration of antiretrovirals must be considered when choosing treatments, mainly in patients with higher CSF viral loads, advanced disease, and CNS disorders associated with significant macrophage activation.

Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy.

OBJECTIVES: To evaluate the impact of response to highly active antiretroviral therapy (HAART) on the natural history of AIDS non-Hodgkin's lymphoma (NHL) and to analyse the feasibility, efficacy and toxicity of HAART in combination with chemotherapy. DESIGN: Prospective observational study in two AIDS clinical centres in Italy. METHODS: All consecutive HIV-infected patients with NHL were included (n = 44; 48% high-risk group) and prospectively followed for 27 months. HAART was administered concomitantly with chemotherapy. The association between response to HAART and clinical presentation, response to chemotherapy and toxicity was analysed by univariate and multivariate models. Survival analysis was performed by Kaplan-Meier estimates and the Cox proportional hazards regression model. RESULTS: A complete response (CR) to chemotherapy was achieved in 71% of HAART responders and 30% of non-responders. Virological response to HAART was the only variable associated with tumour response on multivariate analysis. A higher relative dose intensity (RDI) of chemotherapy was administered in patients with virological response compared with those without. The probability of 1 year survival was higher in patients with virological or immunological response. At Cox regression analysis, immunological response, a higher RDI and a CR to chemotherapy were all associated with a reduced risk of death. CONCLUSION: In HIV-infected patients with NHL, response to HAART was strongly associated with a better response to chemotherapy and prolonged survival. Concurrent treatments were well tolerated, and HAART-responder patients could receive a higher RDI of chemotherapy. In patients with AIDS lymphomas, combining HAART with chemotherapy could be a feasible and effective approach.