Excess liver-related mortality among people with AIDS compared to the general population: an Italian nationwide cohort study using multiple causes of death.

OBJECTIVES: Liver diseases have become a leading cause of death among people with AIDS (PWA). This study aimed to investigate whether PWA experienced excess mortality related to liver diseases as compared to the general population (non-PWA), using a multiple cause of death (MCoD; i.e. all conditions reported on death certificates) approach. METHODS: A population-based, nationwide, retrospective cohort study was conducted among Italian people, aged 15-74 years, who had been diagnosed with AIDS since 2006. Date of death and MCoD data were retrieved, up to December 2015, by individual record linkage with national mortality data. Sex- and age-standardized mortality ratios (SMRs), with 95% confidence intervals (CIs), were estimated by dividing the observed number of deaths related to a specific condition among PWA to the expected number, based on non-PWA mortality rates. RESULTS: Among 7912 PWA (34 184 person-years), 2076 deaths occurred. The number of death certificates reporting liver diseases among MCoDs was 583 (28.1%), including 382 (18.4%) reporting viral hepatitis, 370 (17.8%) reporting nonviral liver diseases, and 41 (2.0%) reporting liver cancers. The corresponding SMRs were 40.4 (95% CI 37.2-43.8) for all liver diseases, 131.1 (95% CI 118.3-145.0) for viral hepatitis, 29.9 (95% CI 27.0-33.1) for nonviral liver diseases, and 11.2 (95% CI 8.1-15.3) for liver cancers. Particularly elevated SMRs emerged among PWA aged 15-49 years and those infected by injecting drug use. CONCLUSIONS: The high excess liver-related mortality observed among PWA warrants preventive actions to limit the burden of viral hepatitis coinfections, alcohol abuse, and metabolic disorders, especially among younger PWA and injecting drug users.

The persistent problem of late HIV diagnosis in people with AIDS: a population-based study in Italy, 1999-2013.

OBJECTIVES: Despite the wide accessibility to free human immunodeficiency virus (HIV) testing and combined antiretroviral therapy (cART), late HIV diagnosis remains common with severe consequences at individual and population level. This study aimed to describe trends of late HIV testing and to identify their determinants in the late cART era in Italy. STUDY DESIGN: We conducted a population-based, nationwide analysis of the Italian National AIDS Registry data (AIDS - acquired immune deficiency syndrome) for the years 1999-2013. METHODS: Late testers (LTs) were defined as people with AIDS (PWA) whose first HIV-positive test preceded AIDS diagnosis by 3 months or less. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were estimated to examine factors associated with being LTs. Joinpoint analysis was used to estimate annual percent changes (APCs) of LTs' proportion over time. RESULTS: Among 20,753 adult PWA, 50.8% were LTs. Italian PWA showed a lower proportion of LTs than non-Italian PWA (46.5% vs 68.2%). Among Italian PWA, the odds of being LTs was higher in men than in women (OR = 2.62, 95% CI: 2.38-2.90); in the age groups below 35 years and over 49 years at diagnosis (OR = 1.24, 95% CI: 1.12-1.37 and OR = 1.51, 95% CI: 1.38-1.67, respectively) vs PWA aged 35-49 years; and in those infected through sexual contact as compared with injecting drug use (OR = 13.34, 95% CI: 12.06-14.76 for heterosexual contact and OR = 8.13, 95% CI: 7.30-9.06 for male-to-male sexual contact). The proportion of LTs increased over time among Italians, especially in the latest period (APC2006-2013 = 5.3, 95% CI: 3.8-6.9). The LTs' proportion resulted higher, though stable, among PWA aged ≥50 years. Conversely, an increasing trend was observed among PWA aged 18-34 years (APC = 5.3, 95% CI: 4.5-6.1). The LTs' proportion was persistently higher among PWA who acquired HIV infection through sexual contact, even if a marked increase among injecting drug users was observed after 2005 (APC = 11.4, 95% CI: 5.7-17.5). CONCLUSIONS: The increasing trend of LTs' proportion in the late cART era highlights the need of new strategies tailored to groups who may not consider themselves to be at a high risk of infection. Active promotion of early testing and continuous education of infection, especially among young people, need to be implemented.

HIV-positive blood donors unaware of their sexual at-risk behaviours before donation in Italy.

BACKGROUND AND OBJECTIVES: Despite the procedures adopted for the selection of blood donors, in Italy the HIV prevalence per 100 000 repeat tested donors (RTD) and first-time tested donors (FTD) is high compared to most other Council of Europe member states. To evaluate the effectiveness of predonation procedures, we studied both the characteristics and the undisclosed risk behaviours of HIV-positive donors. MATERIALS AND METHODS: We analysed the data from the Italian blood donor surveillance system in 2009, 2010 and 2011. Based on the postdonation interview, HIV-positive donors were classified by risk behaviour (heterosexual, MSM, 'non-sexual' and 'not determined') and by time elapsed from risk behaviour to donation. In Italy, the temporary deferral for exposure to behaviour at risk is 4 months. RESULTS: In the postdonation interview, 113 HIV-positive donors (32·4%), who denied at-risk behaviours in the predonation selection, reported sexual risk behaviours <4 months prior to donation; they were predominantly males (84·1%) and RTD (63·7%). The main reason for not having reported the risk behaviour in the predonation selection was 'not realizing having engaged in at-risk behaviour' (66·4%). CONCLUSION: These findings underline the need for more comprehensible educational material, a clearer predonation questionnaire, and effective information campaigns to improve the awareness of HIV sexual risk behaviours among blood donors.

Hepatitis C prevalence in injecting drug users in Europe, 1990-2007: impact of study recruitment setting.

Monitoring injecting drug users' (IDUs) health is challenging because IDUs form a difficult to reach population. We examined the impact of recruitment setting on hepatitis C prevalence. Individual datasets from 12 studies were merged. Predictors of HCV positivity were sought through a multilevel analysis using a mixed-effects logistic model, with study identifier as random intercept. HCV prevalence ranged from 21% to 86% across the studies. Overall, HCV prevalence was higher in IDUs recruited in drug treatment centres compared to those recruited in low-threshold settings (74% and 42%, respectively, P < 0·001). Recruitment setting remained significantly associated with HCV prevalence after adjustment for duration of injecting and recent injection (adjusted odds ratio 0·7, 95% confidence interval 0·6-0·8, P = 0·05). Recruitment setting may have an impact on HCV prevalence estimates of IDUs in Europe. Assessing the impact of mixed recruitment strategies, including respondent-driven sampling, on HCV prevalence estimates, would be valuable.

Epidemiological and clinical characteristics and behaviours of individuals with newly diagnosed HIV infection: a multicentre study in north Italy.

INTRODUCTION: We aimed to investigate socio-demographic, clinical and epidemiological characteristics and behaviours of subjects with new HIV diagnosis. METHODS: We carried out a multi-centre cross-sectional study comprising 17 infectious diseases units in the Lombardy Region, North Italy. All subjects with a first positive test for HIV infection examined in 2008-09 were interviewed using a structured questionnaire. RESULTS: 472 patients were enrolled (mean age 39.8 years, standard deviation [SD] 11.5), mostly males (78%), and born in Italy (77%). The most common routes of HIV transmission were heterosexual intercourse (49%) and sex among men who have sex with men (MSM) (40%). Never/sometimes use of a condom with occasional partners was associated with male gender, heterosexual transmission route, and with >10 sexual partners in their lifetime. 47% had previous HIV negative tests. Having had more than 2 previous HIV negative tests was associated with younger age, MSM transmission route, CD4+ lymphocyte count >350/microl and self-perception of risk. DISCUSSION: This study shows that there is a large portion of the adult population, especially heterosexual men aged 45 years and over, who are at high risk of acquiring and transmitting HIV infection and undergoing the HIV diagnostic test late, due to risk behaviours combined with a low perception of being at risk. Compared to people infected by heterosexual contacts, MSM show a greater awareness of being at risk of infection, but this knowledge has a low impact in reducing at-risk behaviours.

Few Italian drug users undergo HIV testing.

We estimated the proportion of drug users at treatment centres in Italy who had undergone HIV testing and the correlates of testing. Of the 1,917 drug injectors, 37.4% had been tested in the current year; of the 665 non-injectors, 28% had been tested. Among injectors, testing was associated with: being older than 35, foreign nationality, residing in central Italy, drug use for over 2 years, and having undergone both pharmacological and psychological treatment. Among non-injectors, an association was found for foreign nationality and not having been treated at other facilities. The results stress the need to facilitate access to testing.

Pattern of cancer risk in persons with AIDS in Italy in the HAART era.

A record-linkage study was carried out between the Italian AIDS Registry and 24 Italian cancer registries to compare cancer excess among persons with HIV/AIDS (PWHA) before and after the introduction of highly active antiretroviral therapy (HAART) in 1996. Standardised incidence ratios (SIR) were computed in 21951 AIDS cases aged 16-69 years reported between 1986 and 2005. Of 101 669 person-years available, 45 026 were after 1996. SIR for Kaposi sarcoma (KS) and non-Hodgkin lymphoma greatly decreased in 1997-2004 compared with 1986-1996, but high SIRs for KS persisted in the increasingly large fraction of PWHA who had an interval of <1 year between first HIV-positive test and AIDS diagnosis. A significant excess of liver cancer (SIR=6.4) emerged in 1997-2004, whereas the SIRs for cancer of the cervix (41.5), anus (44.0), lung (4.1), brain (3.2), skin (non-melanoma, 1.8), Hodgkin lymphoma (20.7), myeloma (3.9), and non-AIDS-defining cancers (2.2) were similarly elevated in the two periods. The excess of some potentially preventable cancers in PWHA suggests that HAART use must be accompanied by cancer-prevention strategies, notably antismoking and cervical cancer screening programmes. Improvements in the timely identification of HIV-positive individuals are also a priority in Italy to avoid the adverse consequences of delayed HAART use.

[Proportion of drug users in treatment who have never undergone serological testing for HIV, HBV and HCV and correlates of failure to undergo testing: Italy, 2005-2007]. / Proporzione di tossicodipendenti in trattamento che non hanno mai eseguito i test sierologici per HIV, HBV e HCV e fattori correlati alla mancata esecuzione: Italia, 2005-2007.

In Italy, although the most recent guidelines stress the importance of screening for the human immunodeficiency virus (HIV) and the hepatitis B and C viruses (HBV and HCV) those subjects considered to be at high risk (e.g., injecting drug users), not all drug users being treated at public drug dependency centres are regularly tested for these infections. The results of the present study show that 7.2%, 13.0%, and 7.4% of injecting drug users seeking treatment at public drug dependency centres are not tested for, respectively, HIV, HBV and HCV infections and while corresponding figures for drug users who do not inject drugs are 20.3%, 25.1% and 16.2%. The failure to undergo testing among injectors was associated with a shorter history of drug use and with drug centres in central or southern Italy; these associations were also found among non-injectors, with the addition of low level of education. The results stress the importance of facilitating access to testing, of providing the drug dependency centres with the necessary resources for taking blood samples at the centres themselves, of making access to (and performance of) testing uniform throughout the country, and of removing obstacles that can lead to the drug user's refusal to undergo testing.

A comparison between the force of infection estimates for blood-borne viruses in injecting drug user populations across the European Union: a modelling study.

A number of studies have been conducted in injecting drug user (IDU) populations in Europe, in which the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) was measured together with demographic and epidemiological information such as age and the age at first injection. A measure of the risk of becoming infected is the force of infection (FOI), defined as the per capita rate at which susceptible individuals acquire infection. The objective of this study was to estimate the FOI and its heterogeneity for HBV, HCV and HIV (where available) for IDU populations in a number of countries in Europe. Data were obtained from five countries: Belgium, the United Kingdom, Spain and Italy, and the Czech Republic, which provided two data sets. The model describes the prevalence of infection as a function of the FOI that may vary over time or duration of IDU. In addition to this, if two or more infections were being considered then a parameter describing the potential heterogeneity of the FOI within the IDU population was also estimated. The results here add to the growing evidence that new initiates to injecting are at an increased risk of blood-borne viral infection compared with more experienced IDUs. In addition, there is evidence of individual heterogeneity of FOI estimates within the overall IDU populations. This suggests that different proportions of individuals in each population are at increased risk of infection compared with the rest of the population. Future interventions should identify and target these individuals. Moreover, changes over time in individual heterogeneity estimates of IDU populations may provide an indicator for measuring intervention impacts.

Infection with human immunodeficiency virus, herpes simplex virus type 2, and human herpes virus 8 in remote villages of southwestern Papua New Guinea.

To investigate the spread of human immunodeficiency virus (HIV) and other sexually transmitted viruses, two serosurveys (the first in 1999 among 56 adults and the second in 2001 among 351 adults) were conducted in remote villages of the southwestern part of Papua New Guinea. Only one individual was positive for antibodies to HIV. In 2001, the seroprevalence of human herpes virus 8 (HHV-8) was 32.2%, and the seroprevalence of herpes simplex virus type 2 (HSV-2) was 27.4%. Both prevalence rates increased with age, and were lower in the villages near the Bensbach River. The seropositivity of HSV-2 was independently correlated with HHV-8 infection. Our data show that the inhabitants of the southwestern region of Papua New Guinea currently experience an extremely low circulation of HIV. However, the high prevalence of infectious agents that can be sexually transmitted, such as HSV-2 and to a lesser extent HHV-8, indicates the presence of behavioral patterns that may facilitate the spread of HIV in this area of currently low endemicity.

HIV incidence among repeat HIV testers with sexually transmitted diseases in Italy. STD Surveillance Working Group.

OBJECTIVES: To provide data on the incidence of HIV infection among repeat testers with sexually transmitted diseases (STD) in Italy. DESIGN: Retrospective longitudinal study. METHODS: Study participants, enrolled by 47 STD centres throughout Italy, included individuals with a newly diagnosed STD who were tested for HIV at the time of the STD diagnosis and who had a previous documented HIV-negative test. 'Seroconverters' were defined as those individuals who tested HIV-positive at the time of the STD diagnosis. The cumulative and the annual incidence of HIV in this population were estimated. RESULTS: Of 1950 patients, 47 were seroconverters, with an incidence rate of 1.7 per 100 person-years (PY) (95% confidence interval, 1.2-2.2). HIV incidence was higher among males than among females (2.5 versus 0.6 per 100 PY). The highest incidence rate was found among homosexual injecting drug users (IDU) (13.8 per 100 PY), whereas the lowest rate was observed among heterosexual non-IDU (0.4 per 100 PY). The annual incidence decreased from 1.8 per 100 PY in 1989 to 0.9 per 100 PY in 1996. CONCLUSIONS: Our results show that new HIV infections have occurred among STD patients in Italy since 1988, although a clear decrease in incidence has occurred since 1989. However, the rate of seroconversion appears to be alarmingly high in some high-risk groups. These findings suggest that there is a need for continued monitoring of new HIV infections among STD patients, and these individuals may represent a useful sentinel population for a better understanding of the HIV epidemic.

Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. European Study Group on Natural History of HIV Infection in Women.

OBJECTIVES: To assess the impact of HIV-related immunodeficiency and antiretroviral treatment on the occurrence and evolution of abnormal Papanicolaou tests. STUDY DESIGN: Cohort of 485 HIV-infected women with a known date of infection, enrolled during May 1993-April 1998 in 23 centres (gynaecology, infectious disease or STD clinics, or drug treatment centres) in 12 European countries; in 21 centres, follow-up was performed every 6 months (median follow-up: 2 years). METHODS: Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. The prevalence of squamous intraepithelial lesions (SIL), the incidence of SIL and regression from low-grade SIL were studied according to CD4 count after controlling for HPV detection results. RESULTS: Compared with women with CD4 cell counts > 500 x 10(6)/l, women with CD4 cell counts < 200 x 10(6)/l had a twofold increase in both prevalence and incidence of SIL and in non-regression from untreated low-grade SIL; in addition, these women had a lower response rate to treatment of high-grade cervical intraepithelial neoplasia. The increase in SIL incidence associated with a low CD4 cell count was significant in women not receiving antiretroviral treatment (relative risk, CD4 cell count 200-499 x 10(6)/l, 1.9; CD4 cell count < 200 x 10(6)/l, 2.9; CD4 cell count > 500 x 10(6)/l, reference), whereas it was less marked and not statistically significant in treated women. CONCLUSIONS: Severe HIV-related immunodeficiency strongly increases the risk of occurrence of SIL; antiretroviral treatment may reduce this risk, probably by restoring or at least preserving immune function.

Longitudinal analysis of the 90K glycoprotein in the Italian HIV-seroconversion study: temporal trend and predictability of the maturity of HIV infection.

OBJECTIVES: To evaluate the level of 90K as a predictor of AIDS; to describe 90K levels over time after HIV serconversion; and to evaluate the 90K level as a marker of the maturity of infection. DESIGN: Prospective incident cohort of HIV-infected individuals with documented dates of seroconversion. METHODS: Cox models were applied to estimate the crude and adjusted relative hazards (RH) of AIDS by level of 90K. Regression models were applied to describe the temporal trend and the correlates of the level of 90K over time after HIV-seroconversion. Logistic models were applied to evaluate the probability of a sample of 90K having been taken within a certain time period after HIV-seroconversion. RESULTS: The study population consisted of 150 participants of the Italian Seroconversion Study. A total of 429 measurements of 90K were taken. Both early and later measurements of 90K were highly predictive of AIDS, also when adjusting for CD4 lymphocyte count and HIV load. The 90K level (U/ml) increased by 10% annually (95% CI: 7%-13%); the increase over time was linear. IDUs had higher 90K levels than heterosexuals and homosexuals over the course of HIV disease. High 90K levels were highly predictive of distant seroconversions (age-adjusted probability, 74%), whereas were poorly predictive of recent seroconversions (age-adjusted probability, 5%); the results were similar for the predictability of CD4 lymphocyte count. CONCLUSIONS: The level of 90K is a useful prognostic tool for clinical purposes. As a marker of the maturity of infection, 90K is similar to the CD4 lymphocyte count, with the advantage of being able to use serum instead of fresh whole blood. It has a good capacity to identify distant infections.

The national STD surveillance system in Italy: results of the first year of activity. STD Surveillance Working Group.

A prospective STD surveillance system was developed in Italy in 1990. Newly diagnosed cases of sexually transmitted disease (STD) are reported by a network of 45 sentinel STD clinics throughout the country. A total of 10,253 patients were reported between September 1990 and December 1991. The most frequent diagnoses were genital warts (30.8%), non-specific genital infection (male) (12.8%), and non-specific genital infection (female) (11.5%). All patients were asked to undergo an HIV test; 68.4% accepted, of whom 9.3% were seropositive. During the 16-month study period HIV prevalence decreased among IDUs and homo-bisexuals, but increased among non-IDU heterosexuals. These data suggest that STD patients may represent a useful early warning system to detect changes in the epidemic and in the spread of the virus among low-risk heterosexuals. A better counselling programme is needed to improve the acceptance rate of HIV testing among STD patients, and to draw more attention to at-risk sexual behaviours.

Sentinel surveillance of sexually transmitted diseases in Italy.

Statutory notifications suggest that the incidence of gonorrhoea and syphilis have fallen in the past 30 years in Italy, as in other developed countries. Nevertheless, during the 1980s, the annual notification rates in Italy were from 15 to 50 times lower

Surveillance of systemic invasive disease caused by group A Streptococcus in Italy 1994-1996.

In late May 1994, following reports of an outbreak of group A beta-haemolytic streptococcus (GAS) in the United Kingdom, the Istituto Superiore di Sanita (ISS) set up a surveillance system for systemic invasive GAS disease. The surveillance system was als

[STDs today: risk groups and prevention tools]. / Le MST oggi: gruppi a rischio e strumenti di prevenzione.

The importance of specific programs for controlling and preventing sexually transmitted diseases (STD) has been widely recognized, considering that there exists no treatment that results in complection resolution of sexually transmitted viral pathologies, that many STDs have long periods of infectivity and clinical latency, and that there is a high risk of sequelae and of related oncogenesis. However, STD prevention can be quite complex, in that a variety of diseases with diverse clinical and epidemiological characteristics are currently defined as "STDs". One of the main aspects of STD prevention is the identification of population groups considered to be at risk of transmission and that play an important role in maintaining the current epidemic status of STDs in the general population (i.e., sexually promiscuous persons). As with other diseases, the prevention of STDs is generally classified into primary prevention and secondary prevention. Primary prevention consists of protecting healthy individuals from acquiring the infection and mainly consists of promoting safe-sex (including barrier methods), performing vaccination, and conducting information and education campaigns. The objective of secondary prevention is to prevent the disease from further evolving in persons who are already infected or ill, including the prevention of complications, by providing proper medical care and treatment. The main tools of secondary prevention of STDs are: early diagnosis of cases, early and targeted therapy, and management of sexual partners.

[Sexually transmitted diseases and HIV-1 infection in Italian adolescents]. / Le malattie sessualmente trasmesse (MST) e l'infezione da HIV-1 negli adolescenti italiani.

OBJECTIVE: To assess the distribution of specific sexually transmitted diseases (STD), including HIV-1 infection, among Italian adolescents with an acute STD and to evaluate these individuals behavioural characteristics. METHODS: The database of Italy's STD Surveillance System was used as the source of data. Data on all STD cases reported among individuals under 20 years of age were analysed. RESULTS: From September 1990 to December 1997, 57,046 cases of STDs were reported to the surveillance system; 1,757 (3.1%) of these were reported among adolescents, of whom 896 (51.0%) were males. The most commonly reported diseases among males were genital warts (30.7%) and non-gonococcal urethritis (18.5%); among females, the most commonly reported diseases were non-gonococcal vaginitis (39.1%) and genital warts (30.0%). Of the 555 males tested for HIV-1 antibodies, 28 (5.0%) were seropositive; of the 510 females tested, 17 (3.3%) were seropositive. The highest HIV-1 seroprevalence rates were found among intravenous drug users (IDU) (33.3% among male IDUs and 23.8% among female IDUs) and among homosexual males (17.6%). DISCUSSION AND CONCLUSIONS: In Italy, the impact of STDs among adolescents is not negligible, though the distribution of STDs among this population group differs from the distribution among adults. Moreover, the prevalence of HIV-1 among adolescents with STDs is similar to that among adults with STDs. This study's data suggest the need to further develop STD/HIV prevention programmes that specifically target youths.

[Spread of sexually transmitted diseases]. / Diffusione delle malattie sessualmente trasmesse.

The World Health Organization has stressed the importance of preventing and controlling sexually transmitted diseases (STD) at the global level, also in light of the high costs represented by sequaele and complications for both children and adults. In industrialised countries, STD represent the most commonly notified infectious disease. Moreover, in non-industrialised, especially in Africa, STD represent the major reason for which adults seek health care. In Italy, data based on statutory notifications suggest that the incidence of gonorrhoea and syphilis has decreased in the past 20 years, though annual rates are underestimated. This report presents the data collected by the Italian System for the Surveillance of STD.

[Survival in sexually transmitted diseases and HIV infection. Methodology and data flow]. / La sorveglianza delle malattie sessualmente trasmesse e dell'infezione da HIV. Metodologia e flusso dei dati.

Epidemiological surveillance systems are an integral part of programmes geared towards disease control and therapy especially programmes for infectious diseases. In particular, the collection, analysis, and interpretation of data on the spread of sexually transmitted diseases provide the foundation for prevention and control programmes. During the last decade, the lack of data about the diffusion of the emerging STD, such as genital herpes, genital warts and non gonococcal genital infections, has conducted in Italy to set up a STD Surveillance System based on the reporting of cases from selected clinical sites. This report reviews the general principles and methods to be used in setting up of Italian STD Surveillance Project.