Differences in the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals using routine data.

OBJECTIVES: This study was to compare the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals. STUDY DESIGN: We retrospectively analysed data from the COVID-19 Italian integrated surveillance system (14 September 2020 to 17 October 2021). METHODS: We used multivariable Cox proportional hazards models to estimate the hazard ratio (HR) of infection and, among cases, the HRs of death, hospitalisation and subsequent admission to intensive care unit in non-Italian nationals relative to Italian nationals. Estimates were adjusted for differences in sociodemographic characteristics and in the week and region of diagnosis. RESULTS: Of 4,111,067 notified cases, 336,265 (8.2%) were non-Italian nationals. Compared with Italian nationals, non-Italians showed a lower incidence of SARS-CoV-2 infection (HR = 0.81, 95% confidence interval [CI]: 0.80-0.81). However, once diagnosed, they were more likely to be hospitalised (HR = 1.90, 95% CI: 1.87-1.92) and then admitted to intensive care unit (HR = 1.08, 95% CI: 1.04-1.13), with differences larger in those coming from countries with a lower human development index. Compared with Italian cases, an increased rate of death was observed in non-Italian cases from low-human development index countries (HR = 1.41, 95% CI: 1.23-1.62). The HRs of SARS-CoV-2 infection and severe outcomes slightly increased after the start of the vaccination campaign. CONCLUSIONS: Underdiagnosis and delayed diagnosis in non-Italian nationals could explain their lower incidence compared with Italians and, among cases, their higher probability to present clinical conditions leading to worse outcomes. Facilitating early access to vaccination, diagnosis and treatment would improve the control of SARS-CoV-2 transmission and health outcomes in this vulnerable group.

Early childhood vaccination coverage and timeliness by macro-area of origin in children born to foreign women residing in Italy.

OBJECTIVES: Country of origin might affect vaccine uptake in children born to immigrants. We aimed to evaluate differences in childhood vaccination coverage (VC) and timeliness by macro-area of origin of foreign mothers residing in Italy. STUDY DESIGN: Multicentre retrospective birth cohorts. METHODS: We analysed data of 23,287 children born in 2009-2014 to foreign women in the cities of Rome, Turin and Treviso. We retrieved data through record-linkage of the population, vaccination and birth registries. We estimated VCs at different ages for vaccines against tetanus, measles and meningococcal group-C, using the Kaplan-Meier method. Factors associated with vaccine uptake were evaluated using multilevel Poisson models. RESULTS: Estimates of VC at any age and for all antigens were significantly lower in children born to women from Asia and higher in children born to women from Africa, as compared to other macro-areas. Similar differences by area of origin were observed for timeliness; independently of mother's sociodemographic characteristics and neonatal outcomes, the probability of delay vaccination after 2 years of age for each antigen was highest in children born to women from Asia. The risk of missed vaccination for all antigens was significantly higher in children born to younger and unemployed women. CONCLUSIONS: Factors related to area of origin (e.g., cultural habits, language skills) are likely to affect parents' decision to vaccinate their children. These factors, as well as sociodemographic characteristics, should be adequately investigated and addressed to increase vaccine uptake in foreign children, especially those born to Asian women.

Trends of hospitalisations rates in a cohort of HIV-infected persons followed in an Italian hospital from 1998 to 2016.

Here we evaluated hospitalisation rates and associated risk factors of human immunodeficiency virus (HIV)-infected individuals who were followed up in an Italian reference hospital from 1998 to 2016. Incidence rates (IR) of hospitalisations were calculated for five study periods from 1998 to 2016. The random-effects Poisson regression model was used to assess risk factors for hospitalisation including demographic and clinical characteristics. To consider that more events may occur for the same subject, multiple failure-time data analysis was also performed for selected causes using the Cox proportional hazards model. We evaluated 2031 patients. During 13 173 person-years (py) of follow-up, 3356 hospital admissions were carried out for 756 patients (IR: 255 per 1000 py). IR decreased significantly over the study period, from 634 in 1998-2000 to 126 per 1000 py in 2013-2016. Major declines were detected for AIDS-defining events, non-HIV/AIDS-related infections and neurological diseases. Older age, female sex, longer HIV duration and HCV coinfection were associated with a higher hospitalisation risk, whereas higher CD4 nadir and antiretroviral therapy were associated with a reduced risk. Influence of advanced HIV disease markers declined over time. Hospitalisation rates decreased during the study period in most causes. The relative weight of hospitalisations for non-AIDS-related tumours, cardiovascular, respiratory and kidney diseases increased during the study period, whereas those for AIDS-defining events declined.

Clinical predictors and microbiology of ventilator-associated pneumonia in the intensive care unit: a retrospective analysis in six Italian hospitals.

The purpose of this study was to assess the main clinical predictors and microbiological features of ventilator-associated pneumonia (VAP) in the Intensive Care Unit (ICU) environment. This work is a retrospective analysis over one year from September 2010 to September 2011. Patients' risk factors, causes of admission, comorbidities and respiratory specimens collected in six Italian ICUs were reviewed. Incidence and case fatality rate of VAP were evaluated. After stratification for VAP development, univariate and multivariate analyses were performed to assess the impact of patients' conditions on the onset of this infection. A total of 1,647 ICU patients (pts) were considered. Overall, 115 patients (6.9 %) experienced at least one episode of VAP. The incidence rate for VAP was 5.82/1,000 pts-days, with a case fatality rate of 44.3 %. Multivariate analysis showed that admission for neurological disorders (aIRR 4.12, CI 1.24-13.68, p = 0.02) and emergency referral to ICU from other hospitals (aIRR 2.11, CI 1.03-4.31, p = 0.04) were associated with higher risk of VAP, whereas a tendency to a higher risk of infection was detected for admission due to respiratory disease, cardiac disease, trauma and for having obesity or renal failure. A total of 372 microbiological isolates from respiratory specimens were collected in VAP patients. The most common species were Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, showing high resistance rates to carbapenems. Neurological disorders and emergency referral at the admission into the ICU are significantly associated with the onset of VAP. A high incidence of multi-drug resistant Gram- species was detected in the respiratory specimens.

Antiretroviral treatment-based cost saving interventions may offset expenses for new patients and earlier treatment start.

OBJECTIVES: Combination antiretroviral therapy (cART) has become the main driver of total costs of caring for persons living with HIV (PLHIV). The present study estimated the short/medium-term cost trends in response to the recent evolution of national guidelines and regional therapeutic protocols for cART in Italy. METHODS: We developed a deterministic mathematical model that was calibrated using epidemic data for Lazio, a region located in central Italy with about six million inhabitants. RESULTS: In the Base Case Scenario, the estimated number of PLHIV in the Lazio region increased over the period 2012-2016 from 14 414 to 17 179. Over the same period, the average projected annual cost for treating the HIV-infected population was €147.0 million. An earlier cART initiation resulted in a rise of 2.3% in the average estimated annual cost, whereas an increase from 27% to 50% in the proportion of naïve subjects starting cART with a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen resulted in a reduction of 0.3%. Simplification strategies based on NNRTIs co-formulated in a single tablet regimen and protease inhibitor/ritonavir-boosted monotherapy produced an overall reduction in average annual costs of 1.5%. A further average saving of 3.3% resulted from the introduction of generic antiretroviral drugs. CONCLUSIONS: In the medium term, cost saving interventions could finance the increase in costs resulting from the inertial growth in the number of patients requiring treatment and from the earlier treatment initiation recommended in recent guidelines.

Antibiotic prescriptions in the paediatric population in the Lazio Region of Italy: association with children's and physician's characteristics.

BACKGROUND: Estimating prevalence rates for antibacterial use in 0-14 year old children in 2009 in Lazio (Italy). METHODS: Antibiotic prescriptions has been selected as drugs belonging to the J01 main therapeutic of the Anatomical Therapeutic Chemical system. Prevalence data by sex and age were calculated. The proportion of children who underwent 1, 2 or ≥ 3 treatments was calculated. Relation between use of antibiotics and incidence of influenza cases was evaluated. The association of children's and physician's characteristics with prescription was assessed by multi-level Poisson regression model. RESULTS: 45% of children received one antibiotic with a peak in the 1-2 age. Penicillins combinations and beta-lactamase inhibitors were the most frequently prescribed group. Multilevel model highlighted prescription rate decreases with doctor's increasing age, if the doctor is a paediatrician and female. Contrarily, doctors with >900 patients present higher probability to prescribe antibiotics. CONCLUSIONS AND DISCUSSION: The study highlights the variability in antibiotic use and the fact that several children's and primary care doctors' characteristics are associated with antibiotic prescription. Paper findings appear to be coherent with other Italian studies but prevalence rate is definitively higher comparing to other countries.

Effects of Influenza Vaccine on the Immune Responses to SARS-CoV-2 Vaccination.

A number of studies have suggested that influenza vaccination can provide protection against COVID-19, but the underlying mechanisms that could explain this association are still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. A total of 113 participants were enrolled, 74 of whom had no prior COVID-19 diagnosis or significant comorbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARS-CoV-2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARS-CoV-2 vaccinations compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to the influenza vaccine was evaluated, and individuals were stratified as high or low responders. High responders showed increased antibody titers against the SARS-CoV-2 vaccine both after 4 and 12 weeks post-vaccination. Conversely, individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to the vaccine.

Measles outbreak in the Lazio region of Italy: surveillance and impact on emergency departments and hospitalizations.

BACKGROUND: The World Health Organization's (WHO) Regional Office for Europe had committed to 2015 as the year to eliminate measles from the region but several outbreaks have been reported recently from several areas of the continent. Here we describe an outbreak that occurred in 2010-2011 in Lazio region, Central Italy, and its impact on some health care services (i.e., Emergency Departments (EDs) and hospital clinics). METHODS: We analyzed cases of measles reported to the infectious diseases surveillance system and accesses to EDs and hospitalizations for measles in the Lazio Region (central Italy, population of about 5,730,000 people). RESULTS: In 2010-2011, 2,956 cases were reported to the surveillance system (incidence rate: 18.4 and 33.3 per 100,000 in 2010 and 2011, respectively). The incidence rates varied greatly with the territory. The outbreak occurred mainly among children <1 year old and among adolescents, most unvaccinated and did not seem to be related to cases imported from Eastern Europe. Complications were reported in 37.4% of the cases. The epidemic was mainly related to an accumulation of adolescents susceptible to measles due to unsatisfactory vaccination coverage in the early nineties. The outbreak had a strong impact on the health system with 2,881 ED visits and 1,168 hospitalizations. Outbreak-associated costs were considerable. CONCLUSIONS: An additional intervention should be considered aimed at improving routine immunization coverage in children and at planning catch-up vaccination of 6-18 year olds not previously vaccinated. Further, timely surveillance is needed and specific protocols should be implemented to limit secondary cases.

Prevalence of IgM and IgG antibodies to West Nile virus among blood donors in an affected area of north-eastern Italy, summer 2009.

Following reports of West Nile neuroinvasive disease in the north-eastern area of Italy in 2009, all blood donations dating from the period between 1 August and 31 October 2009 in the Rovigo province of the Veneto region were routinely checked to exclude those with a positive nucleic acid test for West Nile virus (WNV). Only one of 5,726 blood donations was positive (17.5 per 100,000 donations; 95% confidence interval (CI): 0.4­97.3). In addition, a selection of 2,507 blood donations collected during the period from 20 July to 15 November 2009 were screened by ELISA for IgG and IgM antibodies against WNV. A positive result was received for 94 of them. The positive sera were further evaluated using immunofluorescence and plaque reduction neutralisation test (PRNT), in which only 17 sera were confirmed positive. This corresponds to a prevalence of 6.8 per 1,000 sera (95% CI: 4.0­10.9). In a case-control study that matched each of the 17 PRNT-positive sera with four negative sera with the same date of donation and same donation centre, we did not find a significant association with age and sex of the donor; donors who worked mainly outdoors were significantly more at risk to have a positive PRNT for WNV.

Suspected transmission of tuberculosis in a maternity ward from a smear-positive nurse: preliminary results of clinical evaluations and testing of neonates potentially exposed, Rome, Italy, 1 January to 28 July 2011.

We report preventive measures adopted after tuberculosis(TB) transmission from a nurse to a newborn assessed in late July 2011. All exposed neonates born between January and July 2011 were clinically evaluated and tested by QuantiFERON TB gold in-tube; newborns testing positive were referred for prophylaxis.Of 1,340 newborns, 118 (9%) tested positive and no other active cases of TB were found. Active surveillance for TB will be continued over the next three years for all those exposed.

[A cross-sectional survey on childhood immunization coverage and reasons of non-compliance in Lazio Region, Italy (2007)]. / Indagine campionaria sulle coperture vaccinali in età pe- diatrica e sui motivi di mancata vaccinazione nella regione Lazio (2007).

During 2007, Laziosanità conducted a cross-sectional survey on childhood immunization coverage in Lazio Region. The survey, implemented in collaboration with the 12 LHUs of the Region, aimed at assessing immunization coverage among children, with 24 months of age or older, at regional and district level. In addition, the survey assessed reliability of the routine surveillance system and immunization records at peripheral level. Finally, delay in immunization schedule, and major reasons for non-compliance, as reported by the mothers, were analyzed. The survey results allowed to identify weakness in the routine surveillance system, low coverage levels for specific LHUs, and strategies for improvement of immunization coverage.

Chronic constipation in hemiplegic patients.

AIM: To assess the prevalence of bowel dysfunction in hemiplegic patients, and its relationship with the site of neurological lesion, physical immobilization and pharmacotherapy. METHODS: Ninety consecutive hemiplegic patients and 81 consecutive orthopedic patients were investigated during physical motor rehabilitation in the same period, in the same center and on the same diet. All subjects were interviewed >= 3 mo after injury using a questionnaire inquiring about bowel habits before injury and at the time of the interview. Patients' mobility was evaluated by the Adapted Patient Evaluation Conference System. Drugs considered for the analysis were nitrates, angiogenic converting enzyme (ACE) inhibitors, calcium antagonists, anticoagulants, antithrombotics, antidepressants, anti-epileptics. RESULTS: Mobility scores were similar in the two groups. De novo constipation (OR = 5.36) was a frequent outcome of the neurological accident. Hemiplegics showed an increased risk of straining at stool (OR: 4.33), reduced call to evacuate (OR: 4.13), sensation of incomplete evacuation (OR: 3.69), use of laxatives (OR: 3.75). Logistic regression model showed that constipation was significantly and independently associated with hemiplegia. A positive association was found between constipation and use of nitrates and antithrombotics in both groups. Constipation was not related to the site of brain injury. CONCLUSION: Chronic constipation is a possible outcome of cerebrovascular accidents occurring in 30% of neurologically stabilized hemiplegic patients. Its onset after a cerebrovascular accident appears to be independent from the injured brain hemisphere, and unrelated to physical inactivity. Pharmacological treatment with nitrates and antithrombotics may represent an independent risk factor for developing chronic constipation.

Human herpesvirus 8 seropositivity and risk of Kaposi's sarcoma and other acquired immunodeficiency syndrome-related diseases.

BACKGROUND: The incidence of Kaposi's sarcoma (KS) is increased severalfold in individuals infected with human immunodeficiency virus-1 (HIV). Human herpesvirus 8 (HHV8) has also been implicated in KS. We investigated several factors that may determine the onset of KS, particularly HHV8 infection in individuals after becoming seropositive for HIV. METHODS: We studied 366 individuals belonging to different HIV-exposure categories (i.e., homosexual activity, intravenous drug use, and heterosexual contact) for whom a negative HIV serologic test and then a positive HIV serologic test were available within a 2-year period. HHV8 antibody testing was performed by use of an immunofluorescence assay on the first serum sample available after the first positive HIV test. Actuarial rates of progression of KS and of other acquired immunodeficiency syndrome (AIDS)-defining diseases were estimated by use of time-to-event statistical methods. All statistical tests were two-sided. RESULTS: Twenty-one of the 366 study participants developed AIDS-related KS, and 83 developed AIDS without KS. One hundred forty (38.3%) participants had detectable anti-HHV8 antibodies. The actuarial progression rate to KS among persons co-infected with HIV/HHV8 was nearly 30% by 10 years after HIV seroconversion. Increasing HHV8 antibody titers increased the risk of developing KS (for seronegative versus highest titer [1:125 serum dilution], adjusted relative hazard [RH] = 51.82; 95% confidence interval [CI] = 6.08-441.33) but not of other AIDS-defining diseases (adjusted RH = 1.14; 95% CI = 0.72-1.80). HHV8-seropositive homosexual men compared with HHV8-seropositive participants from other HIV-exposure categories showed an increased risk of KS that approached statistical significance (adjusted RH = 6.93; 95% CI = 0.88-54.84). CONCLUSIONS: Approximately one third of individuals co-infected with HIV/HHV8 developed KS within 10 years after HIV seroconversion. Progression to KS increased with time after HIV seroconversion. Higher antibody titers to HHV8 appear to be related to faster progression to KS but not to other AIDS-defining diseases.

Relationship between gastrointestinal and extra-gastrointestinal symptoms and delayed gastric emptying in functional dyspeptic patients.

AIM: Delayed gastric emptying and an enlarged fasting gastric antrum are common findings in functional dyspepsia but their relationship with gastrointestinal (GI), and the frequently associated extra-GI symptoms remains unclear. This study evaluated the relationship between GI and extra-GI symptoms, fasting antral volume and delayed gastric emptying in functional dyspepsia. METHODS: In 108 functional dyspeptic patients antral volume and gastric emptying were assessed with ultrasonography (US). Symptoms were assessed with standardized questionnaire. The association of symptoms and fasting antral volume with delayed gastric emptying was estimated with logistic regression analysis. RESULTS: Delayed gastric emptying was detected in 39.8% of the patients. Postprandial drowsiness (AOR 11.25; 95%CI 2.75-45.93), nausea (AOR 3.51; 95%CI 1.19-10.32), fasting antral volume (AOR 1.93; 95%CI 1.22-3.05), were significantly associated with delayed gastric emptying. Symptoms, mainly the extra-GI ones as postprandial drowsiness and nausea, combined with fasting antral volume predicted the modality of gastric emptying with a sensitivity and specificity of 78%. CONCLUSION: In functional dyspeptic patients, (1) an analysis of fasting antral volume and of symptoms can offer valuable indication on the modality of gastric emptying, and (2) it seems appropriate to inquire on postprandial drowsiness that showed the best correlation with delayed gastric emptying.

Incidence and consequences of pregnancy in women with known duration of HIV infection. Italian Seroconversion Study Group.

BACKGROUND: The increasing incidence of human immunodeficiency virus (HIV) infection in women of childbearing age led us to evaluate whether pregnancy affects the natural history of this disease. OBJECTIVES: To conduct a prospective study of women with known dates of HIV seroconversion to describe the incidence and outcome of pregnancy and to assess differences according to age and exposure group. To compare the rate of disease progression between pregnant and nonpregnant women. PATIENTS: All participants, recruited from 14 clinical centers in Italy, had documented HIV-seronegative test results followed by confirmed positive test results within 2 years. RESULTS: A total of 331 women, who had seroconversion between 1981 and 1994, were followed up for a median of 5.5 years from seroconversion; 94 developed HIV-related diseases, 47 developed acquired immunodeficiency syndrome, and 53 had at least 1 CD4 cell count lower than 0.10 x 10(9)/L (< 100 cells/mm3). Thirty-eight women (11.5%) were pregnant at the time of HIV seroconversion and 31 (9.4%) became pregnant after HIV seroconversion (cumulative incidence of pregnancy within 8 years of seroconversion, 28.9%; 95% confidence interval, 21.6%-36.2%). Forty-five (65.2%) of the 69 pregnancies were carried to term. There were no discernible differences in these findings by age or exposure group. Pregnant women did not experience a more rapid rate of progression of disease, even when adjusting for age, exposure group, CD4 cell count, or use of treatment (adjusted relative hazards: HIV-related diseases, 0.72; acquired immunodeficiency syndrome, 0.69; CD4 cell count <0.10 x 10(9)/L, 1.24). CONCLUSION: Women infected with HIV continue to become pregnant after seroconversion, yet pregnancy does not appear to influence the rate of progression of HIV disease.

Trichinella britovi from domestic to wild animals of Sardinia, Italy.

The zoonotic nematode Trichinella britovi has been documented in animals and/or humans of the Mediterranean islands of Corsica and Sardinia since 2004. From 2005 to 2007 in the Sardinia island, several surveys had shown that T. britovi was circulating among backyard and free-ranging pigs reared in the Orgosolo municipality but all attempts had failed to detect this parasite in wild susceptible animals. The aim of the present work was to investigate the circulation of T. britovi in pigs and wildlife of the Orgosolo municipality, and of surrounding municipalities and provinces in the 2010-2014 slaughtering/hunting seasons. The results show that the T. britovi circulation was still restricted to the Orgosolo municipality with a prevalence of 2.6% in free-ranging pigs and 0.2% in backyard pigs but, for the first time, this parasite was detected also in 0.4% of wild boar, and 27.6% of red foxes. No infection was detected in backyard pigs, wild boar, and red foxes of the other municipalities and provinces. Since 1978, African swine fever is endemic in Sardinia and foci of this virus are still active in the investigated areas favoring cannibalism and, consequently, the T. britovi transmission, due to the high mortality rate caused by this virus. This is the first documented report on the transmission of T. britovi between the domestic and the sylvatic cycle. The health authority of the island must provide a service to dispose animal carcasses and offal, stamping out illegal free-ranging pigs, and train hunters and pig owners to manage waste and by-products according to the EU regulations.

CD4 lymphocyte count as a determinant of the time from HIV seroconversion to AIDS and death from AIDS: evidence from the Italian Seroconversion Study.

OBJECTIVES: It is well established that a low CD4 lymphocyte count is strongly associated with an increased risk of AIDS in HIV infection. We attempted to determine whether the link is sufficiently strong that the wide inter-person variability in times from HIV infection to AIDS can be explained solely by differences in CD4 count experience. METHODS: We followed 1090 HIV-infected individuals for up to 12.8 years from seroconversion (median, 3.5 years; 25% for more than 5.2 years). The median interval between last negative and first positive anti-HIV tests was 9 months. A median of four CD4 counts per subject were measured. RESULTS: Individuals with CD4 lymphocyte counts above 250 x 10(6)/l cells experienced an AIDS incidence rate of one per 339 years (0.3 per 100 years; 10 cases in 3394 person-years), compared with one per 6 years in those whose count had declined below this level (17.2 per 100 years; 96 cases in 559 person-years) and one per year in those whose count had declined below 50 x 10(6)/l (100.0 per 100 years; 41 cases in 41 person-years). The AIDS rate increased by an average of 33% [relative rate, 1.33; 95% confidence interval (CI), 1.20-1.49; P = 0.0001] with every year from seroconversion; one per 46 years (2.2 per 100 years) for people seropositive for less than 5 years compared with one per 14 years (7.3 per 100 years) for those seropositive for more than 5 years. After adjusting for the tendency for CD4 lymphocyte counts to be higher soon after seroconversion, the relative rate declined to 1.07 (95% CI, 0.94-1.22) per year from seroconversion (P = 0.32). This result was similar when those infected through sharing injecting equipment, homosexual sex, and other routes were considered separately. The relative rate per year from seroconversion for death due to AIDS fell from 1.41 (P = 0.0001) to 1.00 (P = 0.99) after adjusting for CD4 count. CONCLUSIONS: Most of the inter-person variability in time from HIV infection to AIDS appears to result from differences in CD4 lymphocyte counts. HIV infection appears to cause AIDS and death largely by its ability to induce CD4 lymphocytopaenia or some closely correlated abnormality.

Changes in survival among people with AIDS in Lazio, Italy from 1993 to 1998. Lazio AIDS Surveillance Collaborative Group.

OBJECTIVES: To investigate temporal changes in survival of persons with AIDS (PWA) diagnosed in Lazio, Italy. DESIGN: Longitudinal study of 2862 PWA registered at the AIDS Surveillance System in the period 1 January 1993 to 30 June 1997 and followed for vital status up to 31 May 1998. METHODS: Hazard ratios (HR) of death were calculated by year of diagnosis and by year of follow-up, adjusting for gender, age, modality of exposure, CD4 cell count at diagnosis, and AIDS-defining illness, using the Cox proportional regression model. RESULTS: In the period 1 January 1993 to 31 May 1998, 1914 PWA died. The multivariate model showed a decrease of the risk of death for patients diagnosed from 1995 onward compared with patients diagnosed in 1993 [1995: HR 0.82; 95% confidence intervals (CI) 0.73-0.93; 1996: HR 0.44; 95% CI 0.38-0.51; first semester of 1997: HR 0.47; 95% CI 0.37-0.59]. The model with the year of follow-up modeled as time-dependent variable showed a statistically significant decline in the risk of death starting from the first quarter of 1997 (HR 0.62; 95% CI 0.48-0.80) and reached the minimum in the first two quarters of 1998 (first quarter: HR 0.13; 95% CI 0.08-0.21; second quarter: HR 0.14, 95% CI 0.08-0.25). There was a small difference in the magnitude of the risk estimates among genders, with a slower improvement in survival among females [first semester of 1997 for males HR was 0.51 (95% CI 0.39-0.66) whereas for females HR was 0.80 (95% CI 0.51-1.27)]. CONCLUSIONS: Survival of PWA in a population-based study improved significantly in the era when highly active antiretroviral therapy became available, but such improvement is not homogeneous among genders.

Association between HIV-1 infection and miscarriage: a retrospective study. DIANAIDS Collaborative Study Group. Diagnosi Iniziale Anomalie Neoplastiche AIDS.

OBJECTIVE: To determine the role of HIV-1 infection on miscarriage, we compared the obstetric histories of a cohort of HIV-1-infected and uninfected Italian women. DESIGN: Retrospective study. METHODS: The study participants were women (with at least one reproductive event) with HIV-1 infection or HIV-1-negative sharing the same exposure modalities; all women were attending a network of 16 infectious disease units in 12 Italian cities. Trained interviewers used a standard questionnaire to collect information on obstetric history [i.e., number of pregnancies, pregnancy outcome (live birth, spontaneous or induced abortion) and time of occurrence of these events (i.e., year of birth)]. The association between spontaneous abortion and HIV-1 status at the time of pregnancy was evaluated. RESULTS: The analysis included 272 women and accounted for 480 pregnancies (217 in HIV-infected women, 132 in uninfected women and 131 in women with undefined HIV status) and 60 miscarriages (23 in HIV-infected women, 22 in uninfected women and 15 in women with undefined HIV status). We estimated an adjusted odds ratio of 1.67 between spontaneous abortion and HIV-1 infection. CONCLUSIONS: We observed a 67% increase in risk of spontaneous abortion among HIV-1-infected women compared with HIV-1-negative women. This result should be considered in the counselling and management of women with HIV-1 infection who are of reproductive age.

Increasing survival time after AIDS in Italy: the role of new combination antiretroviral therapies. Tuscany AIDS Study Group.

BACKGROUND: In Italy, antiretroviral combination therapy was adopted in mid-1995 and protease inhibitors in mid-1996. OBJECTIVE: To conduct a prospective, population-based, observational study to evaluate the effect of these therapies on the survival of persons with AIDS (PWA). METHODS: PWA living in the Tuscany region diagnosed between 1985 and 31 March 1997 (National AIDS Registry) were studied. Information on antiretroviral drugs, prophylactic treatment, CD4 cell count, and AIDS-defining illnesses was collected for PWA still alive at 1 January 1996 and those diagnosed thereafter (analysis cut-off date, 30 November 1997). Kaplan-Meier curves were calculated by year of diagnosis. A Cox model was then used to estimate the adjusted (by sex, age, HIV exposure category, CD4 cell count, type and number of AIDS-defining illnesses) relative hazard (RH) of death by year of diagnosis and calendar date (considered as a time-dependent variable). Similar analyses were repeated for PWA diagnosed after 1989, having been stratified by disease-specific AIDS condition. A final analysis was performed for PWA still alive at 1 January 1996 or diagnosed thereafter for estimating the effect of single, double and triple combination therapy (time-dependent variables), having adjusted for the above variables and for prophylactic treatment. RESULTS: A total of 1683 (79.5%) out of 2118 PWA died before 1 December 1997. Use of more potent combination therapies, including protease inhibitors, greatly increased during 1997. Median survival was 2.9, 12.3, 13.4, 11.4 and 17.6 months for diagnoses before 1987, in 1987-1990, 1991-1993, 1994 and 1995, respectively; an estimated 62% of those diagnosed in 1996-1997 had survived 15 months after diagnosis. The Cox model showed a trend of decrease of RH for calendar time starting in the first half of 1996, compared with 1994. When stratifying by specific AIDS-defining disease there was no statistically significant evidence that the improved overall survival was due to increased survival only for certain diseases. The final multivariate analysis for the 771 PWA still alive at 1 January 1996 or diagnosed thereafter estimated significant RH < 1.0 for double and triple therapy (RH, 0.61 and 0.36, respectively) compared with no therapy. CONCLUSIONS: A significant reduction in risk of death after AIDS was observed from the second half of 1996, apparently due to the widespread use of antiretroviral combination therapies.