Evaluation of the Aptima(®) HIV-1 Quant Dx assay for HIV-1 RNA viral load detection and quantitation in plasma of HIV-1-infected individuals: A comparison with Abbott RealTime HIV-1 assay.

The Hologic Aptima(®) HIV-1 Quant Dx assay (Aptima HIV) is a real-time transcription-mediated amplification method CE-approved for use in diagnosis and monitoring of HIV-1 infection. The analytical performance of this new assay was compared to the FDA-approved Abbott RealTime HIV-1 (RealTime). The evaluation was performed using 220 clinical plasma samples, the WHO 3rd HIV-1 International Standard, and the QCMD HIV-1 RNA EQA. Concordance on qualitative results, correlation between quantitative results, accuracy, and reproducibility of viral load data were analyzed. The ability to measure HIV-1 subtypes was assessed on the second WHO International Reference Preparation Panel for HIV-1 Subtypes. With clinical samples, inter-assay agreement for qualitative results was high (91.8%) with Cohen's kappa statistic equal to 0.836. For samples with quantitative results in both assays (n = 93), Lin's concordance correlation coefficient was 0.980 (P < 0.0001) and mean differences of measurement, conducted according to Bland-Altman method, was low (0.115 log10 copies/ml). The Aptima HIV quantified the WHO 3rd HIV-1 International Standard diluted from 2000 to 31 cp/ml (5,700-88 IU/ml) at expected values with excellent linearity (R(2) > 0.970) and showed higher sensitivity compared to RealTime being able to detect HIV-1 RNA in 10 out of 10 replicates containing down to 7 cp/ml (20 IU/ml). Reproducibility was very high, even at low HIV-1 RNA values. The Aptima HIV was able to detect and accurately quantify all the main HIV-1 subtypes in both reference panels and clinical samples. Besides excellent performance, Aptima HIV shows full automation, ease of use, and improved workflow compared to RealTime. J. Med. Virol. 88:1535-1544, 2016. © 2016 Wiley Periodicals, Inc.

a statistical model based on serological parameters for predicting occult HBV infection: implications for organ/ blood donations.

The transmission of hepatitis B virus by donors with occult HBV infection (OBI) is a threat for blood transfusion and organ/tissue transplantation. The risk of carrying HBV DNA is currently not predictable by simple serologic markers, while HBV DNA testing is not universally deployed. This study evaluated an integrated serologic approach for assessing this risk. Anti-HBc positive subjects (461 HIV-negative, 262 HIV-positive) were selected for the study. Serology was analyzed by a commercial CMIA technique. HBV DNA was analyzed by both commercial and home-brew real-time amplification assays. A penalized maximum likelihood logistic approach was used to analyze the data. In HBsAg-negative subjects (HIV-negative), anti-HBc signal/cut off values, the presence of anti-HBc IgM, the absence of anti-HBsAg, and the absence of anti-HCV were correlated to the probability of finding circulating HBV DNA. A model for predicting HBV DNA presence by 4 serological parameters is therefore proposed. The predictive value of the logistic model based on simple serologic markers may represent a reasonable tool for the assessment of HBV transmission risk by transfusion or organ/tissue donation in the context of limited resources and where nucleic acid testing is not performed. In addition, it may be helpful for assessing the risk of reactivation in immunosuppressed OBI patients.

Ability of two commercially available assays (Abbott RealTime HIV-1 and Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 Version 2.0) to quantify low HIV-1 RNA Levels (<1,000 copies/milliliter): comparison with clinical samples and NIBSC working reagent for nucleic acid testing assays.

Concordance between molecular assays may be suboptimal at low HIV-1 viremia levels (<1,000 copies/ml); therefore, it may be difficult to define and compare virologic endpoints for successful and failed therapy. We compared two commercial assays (the Abbott RealTime HIV-1 and the Roche Cobas AmpliPrep/TaqMan HIV-1 version 2.0) for their ability to detect and quantify low viral loads. A comparison was performed using 167 residual clinical samples (with values ranging from "not detected" to 1,000 copies/ml, as measured by the Abbott assay) and the National Institute and Biological Standards and Control (NIBSC) HIV-1 RNA working reagent 1 for nucleic acid amplification techniques (NAT) assays (serially diluted to a range from 1 to 1,000 copies/ml). Quantitative results were compared using Lin's concordance correlation coefficient and a Bland-Altman plot. Concordance with the qualitative results was measured by Cohen's kappa statistic. With clinical samples, the degree of interassay concordance of the qualitative results at a 40-copies/ml HIV-1 RNA threshold was substantial (κ = 0.762); the correlation among the quantified samples was suboptimal (concordance correlation coefficient, 0.728; P < 0.0001); the mean difference of the values between the Roche and Abbott assays was 0.193 log10 copies/ml. Using the HIV-1 RNA working reagent 1 for NAT assays, the results provided by the Roche assay were, on average, 3 times higher than expected, while the Abbott assay showed high accuracy. The Roche assay was highly sensitive, being able to detect a level as low as 3.5 copies/ml HIV-1 RNA with 95% probability. The performance characteristics of each molecular assay should be taken into account when HIV-1 RNA threshold values for "virologic suppression," "virologic failure," "persistent low viral loads," etc., are defined and indicated in the support of clinical decisions.

Temporal trend and characteristics of recent HIV-1 infections: application of an algorithm for the identification of recently acquired HIV-1 infections among newly diagnosed individuals over a 10-year period.

Identification of recent infections (RI) may contribute to improve the quality of human immunodeficiency virus (HIV) surveillance, monitoring ongoing transmission and planning and evaluating prevention programs. Our study applied an algorithm combining clinical and serological information to identify RI in individuals newly diagnosed with HIV in Rome, during the years 1999-2008, in order to describe the trend and characteristics of recently infected individuals. RI were documented seroconverters, or people with an HIV avidity index (AI)<0.80. Individuals with advanced infection (CD4 count <200 cells/?L or AIDS-defining illness) or with AI ?0.80 were considered long-standing infections. Overall, we observed 2,563 new HIV diagnoses. The algorithm was applied in 2124/2563 (82.9%). Of these, 355 were RI (16.7%). RI was found independently associated with calendar year (adjusted odds ratio [aOR]= 1.06, 95% confidence intervals [CI]=[CI 1.02-1.11], for every year of increase), HIV-risk category (men having sex with men: aOR=1.44, [CI 1.04-1.98]; injecting drug users: aOR=1.58, [CI 1.03-2.42] vs. heterosexuals), country of origin (foreign-born: vs Italians: aOR=0.46, [CI 0.33-0.62]), and recruitment site (inpatient vs outpatient clinic: aOR=0.49, [CI 0.37-0.66]). By the application of our algorithm we could characterize the pattern of ongoing HIV transmission, identifying groups needing more urgent prevention programs.

Liver protein profiling in chronic hepatitis C: identification of potential predictive markers for interferon therapy outcome.

The current anti-hepatitis C virus (HCV) therapy, based on pegylated-interferon alpha and ribavirin, has limited success rate and is accompanied by several side effects. The aim of this study was to identify protein profiles in pretreatment liver biopsies of HCV patients correlating with the outcome of antiviral therapy. Cytosolic or membrane/organelle-enriched protein extracts from liver biopsies of eight HCV patients were analyzed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. Overall, this analysis identified 21 proteins whose expression levels correlate with therapy response. These factors are involved in interferon-mediated antiviral activity, stress response, and energy metabolism. Moreover, we found that post-translational modifications of dihydroxyacetone kinase were also associated with therapy outcome. Differential expression of the five best performing markers (STAT1, Mx1, DD4, DAK, and PD-ECGF) was confirmed by immunoblotting assays in an independent group of HCV patients. Finally, we showed that a prediction model based on the expression levels of these markers classifies responder and nonresponder patients with an accuracy of 85.7%. These results provide evidence that the analysis of pretreatment liver protein profiles is valuable for discriminating between responder and nonresponder HCV patients, and may contribute to reduce the number of nonresponder patients exposed to therapy-associated risks.

HIV incidence estimate combining HIV/AIDS surveillance, testing history information and HIV test to identify recent infections in Lazio, Italy.

BACKGROUND: The application of serological methods in HIV/AIDS routine surveillance systems to identify persons with recently acquired HIV infection has been proposed as a tool which may provide an accurate description of the current transmission patterns of HIV. Using the information about recent infection it is possible to estimate HIV incidence, according to the model proposed by Karon et al. in 2008, that accounts for the effect of testing practices on the number of persons detected as recently infected. METHODS: We used data from HIV/AIDS surveillance in the period 2004-2008 to identify newly diagnosed persons. These were classified with recent/non-recent infection on the basis of an avidity index result, or laboratory evidence of recently acquired infection (i.e., previous documented negative HIV test within 6 months; or presence of HIV RNA or p24 antigen with simultaneous negative/indeterminate HIV antibody test). Multiple imputation was used to impute missing information. The incidence estimate was obtained as the number of persons detected as recently infected divided by the estimated probability of detection. Estimates were stratified by calendar year, transmission category, gender and nationality. RESULTS: During the period considered 3,633 new HIV diagnoses were reported to the regional surveillance system. Applying the model, we estimated that in 2004-2008 there were 5,465 new infections (95%CI: 4,538-6,461); stratifying by transmission category, the estimated number of infections was 2,599 among heterosexual contacts, 2,208 among men-who-have-sex-with-men, and 763 among injecting-drug-users. In 2008 there were 952 (625-1,229) new HIV infections (incidence of 19.9 per 100,000 person-years). In 2008, for men-who-have-sex-with-men (691 per 100,000 person-years) and injecting drug users (577 per 100,000 person-years) the incidence remained comparatively high with respect to the general population, although a decreasing pattern during 2004-2008 was observed for injecting-drug-users. CONCLUSIONS: These estimates suggest that the transmission of HIV infection in Lazio remains frequent and men-who-have-sex-with men and injecting-drug-users are still greatly affected although the majority of new infections occurs among heterosexual individuals.

Impact of previous ART and of ART initiation on outcome of HIV-associated tuberculosis.

BACKGROUND: Combination antiretroviral therapy (cART) has progressively decreased mortality of HIV-associated tuberculosis .To date, however, limited data on tuberculosis treatment outcomes among coinfected patients who are not ART-naive at the time of tuberculosis diagnosis are available. METHODS: A multicenter, observational study enrolled 246 HIV-infected patients diagnosed with tuberculosis, in 96 Italian infectious diseases hospital units, who started tuberculosis treatment. A polytomous logistic regression model was used to identify baseline factors associated with the outcome. A Poisson regression model was used to explain the effect of ART during tuberculosis treatment on mortality, as a time-varying covariate, adjusting for baseline characteristics. RESULTS: Outcomes of tuberculosis treatment were as follows: 130 (52.8%) were successfully treated, 36 (14.6%) patients died in a median time of 2 months (range: 0-16), and 80 (32.6%) had an unsuccessful outcome. Being foreign born or injecting drug users was associated with unsuccessful outcomes. In multivariable Poisson regression, cART during tuberculosis treatment decreased the risk of death, while this risk increased for those who were not ART-naive at tuberculosis diagnosis. CONCLUSIONS: ART during tuberculosis treatment is associated with a substantial reduction of death rate among HIV-infected patients. However, patients who are not ART-naive when they develop tuberculosis remain at elevated risk of death.

Determinants of access to experimental antiretroviral drugs in an Italian cohort of patients with HIV: a multilevel analysis.

BACKGROUND: Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy. METHODS: We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately. RESULTS: A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with liver co-morbidity (AOR = 1.44; p = 0.053). and for male homosexuals (vs heterosexuals: AOR = 1.67). Variability of the random effect associated to clinical units was statistically significant (p < 0.001) although no association was found with specific characteristics of clinical unit examined. CONCLUSIONS: Among patients with HIV infection in Italy, access to experimental antiretrovirals seems to be influenced mainly by exhaustion of treatment options and not by socio-demographic factors.

Randomized clinical trial on efficacy of fixed-dose efavirenz/tenofovir/emtricitabine on alternate days versus continuous treatment.

OBJECTIVE: Antiretrovirals with long half-lives, such as tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) and efavirenz (EFV), are suitable for reduced frequency dosing, with potential for improved adherence and reduced toxicity and costs. The objective of this study was to investigate the noninferiority of the TDF/FTC/EFV fixed-dose combination on alternate-days versus standard regimen in virologically suppressed patients. DESIGN: A randomized-controlled open-label noninferiority trial enrolling HIV-1-infected patients treated for at least 6 months with TDF/FTC/EFV fixed-dose combination, virologically suppressed (<40 HIV-RNA copies/ml) with EFV plasma concentrations greater than 1000 ng/ml, were randomized to maintain TDF/FTC/EFV standard-of-care regimen (SOC, Arm A) or to switch to TDF/FTC/EFV on AlTernAte Days (ATAD, Arm B). METHODS: Primary end-point was the proportion of patients with less than 40 HIV-RNA copies/ml at week 48. RESULTS: One hundred and ninety-seven patients were randomized (98 in the SOC and 99 in the ATAD arm). One hundred and seventy-nine (90.3%) were men, median age 43.2 years, 133 (67.5%) MSM. CD4+ T-cell count at baseline was 706 cells/µl in SOC and 632 cells/µl in ATAD arm. At week 48, 95 (96.9%) patients in SOC and 93 (93.9%) in ATAD had a virological response (-3.0% overall risk difference, 95% CI: -8.86%/2.86%). Median change from baseline at week 48 in CD4+ T-cell count was 29.4 cells/µl (95% CI: 2.5/56.4) in SOC (P = 0.008) and 61.0 cells/µl (95% CI: 32.1/89.9) in ATAD (P < 0.001). Median change of EFV concentration at week 48 from baseline was -6.5 ng/ml (95% CI: -103/55) in SOC (P = 0.877) and -1124 ng/ml (95% CI: -1375/-928) in ATAD arm (P < 0.001). CONCLUSION: Despite a significant decrease of EFV exposure, TDF/FTC/EFV on ATAD was noninferior to SOC regimen through 48 weeks.

HIV coinfection and antiretroviral therapy enhances liver steatosis in patients with hepatitis C, but only in those infected by HCV genotype other than 3.

BACKGROUND: Liver steatosis is a common finding in hepatitis C virus (HCV) infection and is associated with an increased progression of the disease. However, HCV genotype 3 steatosis presents a peculiar and virus-induced pathogenesis. We analysed the effect of HIV coinfection and antiretroviral therapy on hepatic steatosis and the effect of the steatosis on fibrosis in patients with or without HCV genotype 3 infection. METHODS: All consecutive HIV-infected and uninfected patients who had undergone a liver biopsy for evaluation of HCV infection at the Infectious Diseases Clinic (Modena, Italy) were included in this study. Primary outcomes were the presence or absence of steatosis or the presence of moderate or advanced fibrosis. RESULTS: A total of 284 patients were enrolled: 187 infected by HCV and 97 coinfected with HIV and HCV. In HCV genotype 3 patients, only HCV-related variables, such as plasma HCV RNA levels (odds ratio [OR] per log10 1.68, P < 0.001) and estimated duration of HCV infection (OR per year 1.17, P = 0.004) were associated with steatosis. In patients infected with other HCV genotypes, steatosis was associated with older age (OR per 5 years 1.47, P < 0.001), with exposure to d-drugs in HIV-HCV-coinfected patients (OR 2.60, P = 0.04) and specifically exposure to stavudine (OR 2.76 HIV-HCV-coinfected versus not HIV-infected patients, P = 0.04). Steatosis was independently associated with bridging fibrosis only in patients infected by HCV genotype other than 3 (OR 4.03, P = 0.01). CONCLUSIONS: Hepatic steatosis, in both HCV-monoinfected and in HIV-HCV-coinfected patients, is strongly correlated with HCV genotype 3, probably through interactions between HCV virus and liver cells. HIV-related increase of steatosis in patients with HCV is probably related to antiretroviral drugs, especially stavudine, in patients infected by HCV genotype other than 3.

[Kidney transplant and cancer risk: an epidemiological study in Northern and Central Italy]. / Trapianto di rene e rischio di cancro: studio epidemiologico in Nord e Centro Italia.

OBJECTIVE: This investigation aimed at highlighting the cancer risk of recipients of kidney transplant in northern and central Italy. METHODS: Data on 2,120 kidney transplant recipients from Niguarda Ca' Granda Hospital Milan, or from Policlinico "A. Gemelli", Rome, were analyzed The period at risk of developing cancer (person-years, PY) was computed from 30 days after transplant to date of cancer diagnosis, or date of death, or date of re-entering dialysis, or date of last follow-up. Observed and expected numbers of cancer were compared through sex- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). The transplant attributable fraction (AF) of cancer cases and incidence rate ratios (IRR) were also computed. RESULTS: After 16.594 PY of follow-up (median flow-up: 6.8 years), 121 cancer cases were diagnosed (729.2 cases/10(5) PY). The SIR for all cancers was 1.9. Kaposi's sarcoma (KS) (27 cases observed, SIR = 82) and non-Hodgkins lymphoma (NHL) (18 cases observed a SIR = 6.4 were the most common cancers. Significantly increased SIRs were also noted for native kidney (11 cases observed SIR = 4.9), corpus uteri (6 cases observed SIR = 4.6), and liver (6 cases observed, SIR = 3.1). The transplant AF was 46.9%, largely due to KS (98.8%) and NHL (84.3%). Since SIRs decreased with increasing age, the transplant AF ranged from 73.2% below 45 years of age to 30.4% after 54. Among risk factors, area of birth strongly influenced the risk of KS, with a 3-fold higher risk in those born in the South of Italy as compared to those born in the northern part. CONCLUSIONS: Immune depression after kidney transplantation entails a two-fold increased overall risk of cancer, mainly related to cancers associated to a viral aetiology. Furthermore, our findings suggest the need to adopt a specific serological screening for the prevention of post-transplant KS in individuals born in southern Italy.

Risk of cancer following immunosuppression in organ transplant recipients and in HIV-positive individuals in southern Europe.

This investigation highlighted the risk of cancer in 8074 HIV-infected people and in 2875 transplant recipients in Italy and France. Observed and expected numbers of cancer were compared through sex- and age-standardised incidence ratios (SIRs) and 95% confidence intervals (CIs). After 15 years of follow-up, the cumulative probability of cancer was 14.7% in transplant recipients and 13.3% in HIV-positives. The SIRs for all cancers were 9.8 in HIV-positives and 2.2 in transplants. Kaposi's sarcoma (SIR=451 in HIV-positives, 125 in transplants) and non-Hodgkin lymphoma (SIR=62 and 11.1, respectively) were the most common cancers. A significantly increased SIR for liver cancer also emerged in both groups. The risk of lung cancer was significantly elevated in heart transplant recipients (SIR=2.8), and of borderline statistical significance in HIV-positive people (95% CI:0.9-2.8). Immune depression entails a two-fold increased overall risk of cancers, mainly related to cancers associated with a viral aetiology.

Role of previous hospitalization in clinically-significant MRSA infection among HIV-infected inpatients: results of a case-control study.

BACKGROUND: HIV-infected subjects have high incidence rates of Staphylococcus aureus infections, with both methicillin-susceptible and methicillin-resistant (MRSA) strains. Possible explanations could include the high burden of colonization, the behavioral risk factors, and the frequent exposures to health care facilities of HIV-infected patients. The purpose of the study was to assess the risk factors for clinically- significant methicillin-resistant Staphylococcus aureus (CS-MRSA) infections in HIV-infected patients admitted to Infectious Diseases Units. METHODS: From January 1, 2002 to December 31, 2005, we conducted a retrospective case-control (1:2) study. We identified all the cases of CS-MRSA infections in HIV-infected patients admitted to the National Institute for Infectious Diseases (INMI) "Lazzaro Spallanzani" in the 4-year study period. A conditional logistic regression model was used to identify risk factors for CS-MRSA infection. RESULTS: We found 27 CS-MRSA infections, i.e. 0.9 CS-MRSA infections per 100 HIV-infected individuals cared for in our Institute. At multivariate analysis, independent predictors of CS-MRSA infection were cumulative hospital stay, invasive procedures in the previous year, and low CD4 cell count. Particularly, the risk for CS-MRSA increased by 14% per an increase of 5 days hospitalization in the previous year. Finally, we identified a low frequency of community-acquired MRSA infections (only 1 of 27; 3.7%) among HIV-infected patients. CONCLUSION: Clinicians should be aware of the risk for CS-MRSA infection in the clinical management of HIV-infected patients, especially in those patients with a low CD4 cell count, longer previous hospital stay, and previous invasive procedures.

Gender differences in clinical progression of HIV-1-infected individuals during long-term highly active antiretroviral therapy.

OBJECTIVE: To assess gender differences in the long-term clinical, virological and immunological outcomes during highly active antiretroviral therapy (HAART). METHODS: This longitudinal observational multicentre study followed 2460 HIV-infected patients who had begun a protease inhibitor-based regimen for a median period of 43 months. Outcome measures were virological suppression (< 500 copies/ml), confirmed virological rebound after suppression, and death or new AIDS-defining illness (ADI). RESULTS: At baseline, 690 female patients (28.0%) had significantly lower age, higher prevalence of heterosexual contact and lower prevalence of intravenous drug use as risk factors for HIV infection compared with males. Furthermore, females had a lower number of AIDS-defining illnesses, higher CD4 cell counts and lower viral loads. No gender differences were reported in terms of proportion of patients achieving viral suppression or exhibiting rebound after achieving viral suppression. Female patients experienced reduced clinical progression during follow-up compared with males (P = 0.008) by Kaplan-Meier analysis; however this difference was not significant in an adjusted analysis. In a multivariate model, the interaction between gender and risk factor for HIV or viral load showed that female drug users and female patients with a baseline HIV RNA viral load of 10(4)-10(5) copies/ml had a favourable clinical outcome compared with males (P = 0.035 and P = 0.015, respectively). CONCLUSION: No differences were found between genders in terms of virological and immunological outcomes during long-term HAART. Nevertheless, a lower risk of clinical progression was reported among female patients with intermediate baseline viral load than in males.

Kaposi's sarcoma in transplant and HIV-infected patients: an epidemiologic study in Italy and France.

BACKGROUND: A follow-up study was conducted in Italy and in France to compare the epidemiology of Kaposi's sarcoma (KS) between human immunodeficiency virus (HIV)-infected people and transplant recipients. METHODS: In all, 8,074 HIV-positive individuals (6,072 from France and 2,002 HIV-seroconverters from Italy) and 2,705 Italian transplant recipients (1,844 kidney transplants, 702 heart transplants, and 159 liver transplants) were followed-up between 1970 and 2004. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were computed to estimate the risk of KS, as compared to sex- and age-matched Italian and French populations. Incidence rate ratios (IRRs) were used to identify risk factors for KS. RESULTS: A 451-fold higher SIR for KS was recorded in HIV-infected subjects and a 128-fold higher SIR was seen in transplant recipients. Significantly increased KS risks were observed in HIV-infected homosexual men (IRR=9.7 in France and IRR=6.7 in Italy vs. intravenous drug users), and in transplant recipients born in southern Italy (IRR=5.2 vs. those born in northern Italy). HIV-infected patients with high CD4+ cell counts and those treated with antiretroviral therapies had reduced KS risks. In relation to duration of immunosuppression, KS occurred earlier in transplant patients than in HIV-seroconverters. CONCLUSIONS: This comparison highlighted that the risk of KS was higher among HIV-infected individuals than in transplant recipients, and that different co-factors are likely to influence the risk of KS. Moreover, the early KS occurrence in transplant recipients could be associated with different patterns of progressive impairment of the immune function.

Epidemiological aspects of major opportunistic infections of the respiratory tract in persons with AIDS: Europe, 1993-2000.

OBJECTIVE(S): To describe the epidemiology of Pneumocystis carinii pneumonia (PCP), pulmonary tuberculosis (PTB) and recurrent bacterial pneumonia (RBP) as AIDS-defining illnesses (ADI) in Europe. DESIGN: Analysis of AIDS surveillance data collected in the World Health Organization European region by EuroHIV, Saint Maurice, France. METHODS: Adult AIDS cases notified between 1993 and 2000 were studied. Since AIDS diagnosis may be constituted by up to four concurrent illnesses, polytomous logistic regression odds ratios (OR) and 95% confidence intervals (CI) were computed. Time trends and correlates of PCP, PTB or RBP were assessed. RESULTS: There were 181 296 ADI among the 142 447 AIDS cases included in this study. PCP was the commonest ADI in western Europe (17.8%) and PTB (20.4%) was the commonest ADI in eastern Europe. Within western Europe, PTB was more common in the south than in the north (OR, 1.5) and increased steadily over time. RBP increased until 1998 (from 1.9% to 3.7%) and thereafter declined. Young age was associated with an excess risk for PTB and, in comparison with heterosexuals, homosexual men were at higher risk for PCP (OR, 1.3). Injecting drug users (IDU) (OR, 2.8; 95% CI, 2.6-3.1) and recipients of blood (OR, 1.7; 95% CI, 1.4-2.2) were at increased risk for RBP. CONCLUSIONS: This analysis highlighted the continuing importance of PCP and the increasing importance of PTB as an ADI in western Europe, and it emphasized the need to investigate more thoroughly the vast epidemic of AIDS-associated PTB in eastern Europe. IDU and recipients of blood should be considered as target groups for vaccination against RBP.

[Time trends in infectious disease mortality in Italy: 1969-1999]. / Andamenti della mortalità per malattie infettive in Italia: 1969-1999.

OBJECTIVE: To describe the global impact of infectious diseases on mortality in Italy from 1969 to 1999. DESIGN: Statistical analysis of routinely collected mortality data, using a revised definition of infectious causes of death based on target organs. SETTING: The present paper summarizes time trends of infectious disease mortality widely discussed in the Atlas "30 Anni di Malattie Infettive in Italia: Atlante di Mortalità". MAIN OUTCOME MEASURES: Age standardized mortality rates (/100,000); standardized mortality ratios (SMR); percentage of deaths attributable to infectious diseases. RESULTS: Apart from HIV infection and AIDS, infectious diseases were responsible of 1.7% of the overall mortality that occurred in Italy in the study period: 57.5% of such deaths were not included in the ICD8 and ICD9 codes for infectious diseases. The mortality for all infectious diseases showed a very strong downward trend up to 1994, (with a 6-fold decline). Thereafter, a slight increase in deaths for septicaemias, heart infections and hepatitis was recorded. Over time, an increasing proportions of deaths due to infections occurred in the elderly (i. e., > or = 65 years of age), from 48.1% in 1969-1979 to 77.3% in 1990-1999. Mortality rates were consistently higher in men than in women, and showed a substantial geographic heterogeneity. In newborns, from 1969 thru 1999 mortality rates declined 10-fold all over the country, but an inverse north-south geographic gradient persisted during the whole study period. The spread of HIV infection and AIDS epidemic in the first '80s dramatically interrupted the downward trend in infectious disease mortality outlined above. Between 1993 and 1996, HIV/AIDS was the main cause of death among Italian men aged 30 to 39 years. CONCLUSIONS: This statistical analysis allowed to better quantify the impact of infectious diseases on overall mortality in Italy. Observed time trends were in accordance to the picture recorded in other western Countries, whereas the higher newborn mortality in southern Italy reflects the persistence of geographical inequalities in the health care organization.

No impact of interleukin-28B polymorphisms on spontaneous or drug-induced hepatitis delta virus clearance.

BACKGROUND: rs12979860 and rs8099917 interleukin-28B polymorphisms are associated with spontaneous or interferon-alpha induced hepatitis C clearance, "CC" and "TT" genotypes (respectively) being the most favourable. There are no data on the influence of interleukin-28B polymorphisms on hepatitis delta clearance in hepatitis B/D co-infected patients. AIMS: The present study explores the potential influence of both rs12979860 and rs8099917 polymorphisms on delta infection outcome. METHODS: Retrospective-longitudinal study on 55 European patients observed for at least 4 years, selected from a cohort of 439 subjects positive for hepatitis delta antibodies and hepatitis B core antibodies. The rate of spontaneous and interferon induced delta-RNA clearance was compared in interleukin-28B rs12979860 "CC" vs "non CC", and in rs8099917 "TT" vs "non TT" genotypes. RESULTS: Prevalence of rs12979860C allele was 60%, consistent with the reported prevalence in Italy (67%, p=0.128). No significant differences in spontaneous clearance rate were observed between rs12979860 "CC" and "non CC" genotypes (13.3% vs 7.5%, respectively, p=0.60), and between rs8099917 "TT" and "non-TT" genotypes (11.1 vs 7.1%, respectively, p=0.67). No differences were observed for interferon-induced delta-RNA clearance either. CONCLUSIONS: Our data suggest that interleukin-28B polymorphisms might not influence hepatitis delta clearance rate in either natural history or interferon-alpha response.

Access to treatment for HBV infection and its consistency with 2008 European guidelines in a multicentre cross-sectional study of HIV/HBV co-infected patients in Italy.

BACKGROUND: A survey was performed in 2008 to evaluate the profiles of patients with chronic hepatitis B cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes: i) factors associated with access to the anti-HBV treatment in a cohort of HIV/HBV co-infected patients cared for in tertiary centers of a developed country with comprehensive coverage under the National Health System (NHS); ii) consistency of current anti-HBV regimens with specific European guidelines in force at the time of the study and factors associated with the receipt of sub-optimal regimens. METHODS: The study focuses on 374 (87.6%) treated patients at some point in their life out of the 427 tested HIV/HBV positive. It is multicentre, cross-sectional in the design. To account for missing values, a Multiple Imputation method is used. RESULTS: Three hundred and thirty-four (89.3%) patients were currently treated. The most common current regimen was combination therapy of tenofovir (TDF) plus LAM/FTC (lamivudine/emtricitabine) (n = 235, 70.4%), as part of antiretroviral treatment. In the multivariate analysis, an increased chance of getting treated was independently associated with increasing years since HBV diagnosis (2-10 years, p <0.001; >10 years, p <0.001). Patients consistently treated with European AIDS Clinical Society (EACS) 2008 guidelines were 255 (76.6%), of whom 202 (79.2%) with an indication to an anti-HIV treatment, 30 (11.8%)without an indication, and 21 (8.2%) with cirrhosis. Among the 78 not-consistent patients, LAM mono-therapy (n = 60, 76.9%) was the most common regimen, 34 (56.7%) of them showing HBV DNA load below 1x10(3) IU/mL. Previous anti-HBV treatment (p = 0.01) and a triple HDV co-infection (p = 0.03) reduced the chance of not-consistent regimens. Conversely, HCV co-infection was independently associated with an increased odds ratio of being inconsistently treated (p = 0.004). CONCLUSION: Our study shows that Italian IDCs treat for HBV infection the vast majority of HIV/HBV co-infected patients with no disparities limiting access to antiviral therapy. In approximately two-thirds of the patients on treatment, anti-HBV regimens are consistent with 2008 EACS guidelines. Finally, our study identifies scenarios in which clinical practice deviates from recommendations, as in case of sub-optimal regimens with effective anti-HBV response.