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.

A new surveillance gynecological network to assess the incidence and prevalence of genital warts in the Italian female population: lessons learned.

Human papillomavirus (HPV) is the etiologic agent of genital warts. Genital warts are transmitted through sexual contacts and caused in about 90% of the cases by HPV types 6 and 11. Worldwide, several million cases of genital warts occur each year both in females and males. In Italy, genital warts are not subject to mandatory notification; the only available data come from the sentinel surveillance system for sexually transmitted infections (STI), which show that external genital warts represent the most frequent STI in Italy. However, these data are not suitable for estimates of incidence and prevalence of single STI in the general population. To obtain more reliable data on the epidemiology of genital warts in the female population at large, we implemented a network of local gynecologists reporting essential data on all women visited throughout one year and detailed data on women who were diagnosed with genital warts. In order to organize and create this network, a partnership between the Italian National Institute of Health and the Italian Society of Gynecology and Obstetrics was constituted to implement the start-up and management of this pilot and unique project in Europe. The present paper intends to present the methods used to build and implement this surveillance network of local gynecologists.

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.

[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.

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.

Phenotypic and genotypic characterization of Neisseria gonorrhoeae in parts of Italy: detection of a multiresistant cluster circulating in a heterosexual network.

Data concerning Neisseria gonorrhoeae infections in Italy are scarce, and there is little information on the phenotypic and genotypic characteristics of the circulating strains. In this study, 326 isolates collected from 397 patients, with or without concurrent human immunodeficiency virus (HIV) infection, were cultured and characterized by serovar and antimicrobial susceptibility to five antimicrobials. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was also performed for strain characterization and to identify a transmission network. Gonococcal infection was diagnosed in 364 males and 33 females, 296 of whom were Italian and 96 of whom were foreigners (nationality was unknown in five cases). Among the 364 males, 197 were heterosexual, and the median age was 31 years. Approximately 8.3% of all the investigated patients were HIV-1-positive. The isolates were assigned to three different serovars (IA, IB, IA/IB), IB being the most frequently encountered. A significant rate of resistant gonococci was also observed; 34%, 25.5% and 19.1% of ciprofloxacin-resistant, penicillin-resistant and tetracycline-resistant phenotypes, respectively, were detected, and 10.2% of strains were multidrug-resistant. Together with the presence of different sequence types (STs), identified by NG-MAST, a multidrug-resistant cluster, ST661, was detected in a heterosexual network in a precise geographical area of the country. In particular, all strains belonging to ST661 showed identical profiles according to pulsed-field gel electrophoresis (PFGE), all were serotype IB, and all were resistant to penicillin, ciprofloxacin and tetracycline.

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.

Correlates of HIV, HBV, and HCV infections in a prison inmate population: results from a multicentre study in Italy.

A cross-sectional study was undertaken on the correlates of infection for the human immunodeficiency virus (HIV) and hepatitis viruses B and C (HBV and HCV) in a sample of inmates from eight Italian prisons. A total of 973 inmates were enrolled [87.0% males, median age of 36 years, 30.4% intravenous drug users (IDUs), 0.6% men who have sex with men (MSWM)]. In this sample, high seroprevalence rates were found (HIV: 7.5%; HCV: 38.0%; anti-HBc: 52.7%; HBsAg: 6.7%). HIV and HCV seropositivity were associated strongly with intravenous drug use (OR: 5.9 for HIV; 10.5 for HCV); after excluding IDUs and male homosexuals, the HIV prevalence remained nonetheless relatively high (2.6%). HIV prevalence was higher for persons from Northern Italy and Sardinia. The age effect was U-shaped for HIV and HCV infections; HBV prevalence increased with age. Tattoos were associated with HCV positivity (OR: 2.9). The number of imprisonments was associated with HIV infection, whereas the duration of imprisonment was only associated with anti-HBc. The probability of being HIV-seropositive was higher for HCV-seropositive individuals, especially if IDUs. In conclusion, a high prevalence of HIV, HCV, and HBV infections among inmates was observed: these high rates are in part attributable to the high proportion of IDUs. Frequency of imprisonment and tattoos were associated, respectively, with HIV and HCV positivity. Although it is possible that the study population is not representative of Italy's prison inmate population, the results stress the need to improve infection control measures users was prisons.

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.

Correlates of human herpes virus-8 and herpes simplex virus type 2 infections in Northern Cameroon.

The association between sexual activity and human herpes virus-8 (HHV-8) infection has been established, but the mode of acquisition is still unclear. Blood samples from 238 individuals from Northern Cameroon were tested to evaluate the incidence of herpes simplex virus-2 (HSV-2), human immunodeficiency virus (HIV), Treponema pallidum, and HHV-8 infections and to identify their possible association. The presence of HSV-2 antibodies was associated significantly with gender, age, and HIV, HHV-8 antilatent, and T. pallidum antibodies, but not with HHV-8 antilytic antibodies. In a multivariate model older age, female gender, seropositivity for HIV, for HHV-8 latent antigens and for T. pallidum were associated independently with seropositivity for HSV-2. HSV-2-seropositive individuals had significantly higher titers of antibodies to both lytic (P = 0.019) and latent (P = 0.021) HHV-8 antigens. These results suggest that HSV-2 infection can contribute to sexual transmission of HHV-8 infection.

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.

Human herpesvirus-8 and other viral infections, Papua New Guinea.

We studied residents of remote villages and the capital (Port Moresby) of Papua New Guinea to determine the distribution of human herpesvirus-8 (HHV-8) infection. Our data suggest that HHV-8 has been endemic on the island for a long time and that the epidemiologic pattern of HHV-8 is more similar to that of herpes simplex virus-2 than hepatitis C virus.

Prevalence and risk factors for herpes simplex virus type 2 infection among adolescents and adults in northern Cameroon.

BACKGROUND: A number of surveys have reported a high prevalence of herpes simplex virus type 2 (HSV-2) infection in south central and east central Africa. GOAL: To evaluate the distribution and modes of HSV-2 transmission in northern Cameroon. STUDY DESIGN: A serosurvey was conducted among 194 adolescents and adults in a Cameroon hospital. Antibodies against HSV-2 were detected by a gG2-specific enzyme-linked immunoabsorbent assay. RESULTS: The prevalence of HSV-2 antibodies was found to be 37.1%. In the multivariate analysis, female gender, no condom use, a positive syphilis serology, and HIV infection were significantly associated with HSV-2 infection. CONCLUSIONS: The current findings show that the HSV-2 seroprevalence in northern Cameroon is high and similar to that found in other African countries. HSV-2 infection represents a marker for at-risk sexual behavior and may be a common cofactor for HIV transmission in this geographic area.

Incidence of invasive cervical cancer in a cohort of HIV-seropositive women before and after the introduction of highly active antiretroviral therapy.

To assess whether the incidence of invasive cervical cancer (ICC) has changed as a result of highly active antiretroviral therapy (HAART), we conducted a prospective cohort study on the incidence of ICC before and after the introduction of HAART among Italian women with a known duration of HIV infection. We estimated the incidence per 1000 person years of ICC as a first AIDS-defining disease for the periods 1981 through 1991, 1992 through 1995, and 1996 through 1998. We also estimated the incidence of other first AIDS-defining diseases. Kaplan-Meier and Cox models were applied to compare the periods 1981 through 1995 and 1996 through 1998 in terms of cumulative incidence and relative hazards (RHs). The analysis included 483 women (median follow-up: 7 years). In the period 1981 through 1995, a trend of increase was observed in the incidence of ICC and other AIDS-defining diseases; this trend has continued only for ICC, whereas the incidence of other AIDS-defining diseases has decreased since 1996. Compared with 1981 through 1995, the RH of ICC for 1996 through 1998 was 7.41 (95% confidence interval [CI]: 1.21--45.44); when adjusting for age at HIV seroconversion, the RH decreased to 4.75 (95% CI: 0.80--28.24). It remains to be determined whether the continued increase in ICC incidence after the introduction of HAART is attributable to a decreasing competitive mortality from other AIDS-defining diseases among HIV-infected women.