In this decade, the global prevalence of HIV-1 infection stabilized at 0.8% (range: 0.7-0.9%). However, important regional differences in trends and mode of transmission: Sub-Saharan Africa is the most affected by HIV. Since 2001, the number of people with HIV in Eastern Europe and Central Asia increased from 650,000 to 1,5 million in 2007. Overall trends were stable in Central and Western Europe. Heterosexual and homosexual transmission accounts for the largest proportion in these regions. Transmission among injecting drug users has decreased. Similar trends have been observed in Italy: in 2007, there were 1,679 new diagnoses, equivalent to an incidence of 6,0 per 100,000 population. Over the years there has been a progressive increase in the proportion of diagnoses among women and in the median age at diagnosis, as well as changes in the exposure categories (i.e. a decrease in the proportion of injecting drug users and an increase in infections attributed to homosexual and heterosexual contacts). The era of combination antiretroviral therapy (cART) has resulted in a reduction of morbidity and mortality. Before the advent of cART in 1996, the main causes of morbidity and mortality in people with HIV were the opportunistic infections and malignancies AIDS associated.
The human immunodeficiency virus (HIV) epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission.Protease and reverse transcriptase sequences from 876 new HIV diagnoses (April 2013-March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥2 sequences, ≥80% local branch support, and maximum genetic distance of all sequence pairs in the cluster ≤2.5%. Recent infection was determined through the limiting antigen avidity enzyme immunoassay. Sequences were analyzed for transmitted drug resistance mutations.Thirty percent of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (odds ratio [OR], 4.38 [95% confidence interval {CI}, 2.56-7.50]); risk group (OR, 5.65 [95% CI, 3.27-9.75]) for men who have sex with men compared to heterosexual males; recent, compared to long-standing, infection (OR, 2.72 [95% CI, 1.64-4.52]); reported sex work contact (OR, 1.93 [95% CI, 1.07-3.47]); and younger age groups compared with age ≥36 years (OR, 1.83 [95% CI, 1.10-3.05] for age ≤25 years). Females were associated with lower odds of clustering than heterosexual males (OR, 0.49 [95% CI, .31-.77]). In multivariate analysis, risk group, subtype, and age group were independently associated with clustering (P < .001, P = .007, and P = .033, respectively). Eighteen sequences (2.1%) indicated evidence of transmitted drug resistance.Our findings suggest high levels of transmission and bridging between risk groups.
Outbreaks of acute hepatitis C virus (HCV) infection among HIV-infected MSM have been described since 2000. However, phylogenetic analysis suggests that the spread of HCV started around 1996. We estimated the incidence of HCV in HIV-infected MSM with well estimated dates of HIV seroconversion from 1990 to 2007.Data from 12 cohorts within the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) Collaboration were used. HCV incidence was estimated using standard incidence methods and methods for interval-censored data. We accounted for the fact that routine HCV data collection in each cohort started in different calendar years.Of 4724 MSM, 3014 had an HCV test result and were included. Of these, 124 (4%) had only positive HCV test results, 2798 (93%) had only negative results and 92 (3%) had both. In 1990, HCV incidence ranged from 0.9 to 2.2 per 1000 person-years, depending on the analysis strategy used. HCV incidence increased up to 1995 when it was estimated to range between 5.5 and 8.1 per 1000 person-years. From 2002 onwards, it increased substantially to values between 16.8 and 30.0 per 1000 person-years in 2005 and between 23.4 and 51.1 per 1000 person-years in 2007.Our data support phylodynamic findings that HCV incidence had already increased among HIV-infected MSM from the mid-1990s. However, the main expansion of the HCV epidemic started after 2002. Incidence estimates obtained from cohort studies may help identify changes in the spread of important infections earlier and should guide routine testing policies to minimize further disease burden.
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.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.All participants, recruited from 14 clinical centers in Italy, had documented HIV-seronegative test results followed by confirmed positive test results within 2 years.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).Women infected with HIV continue to become pregnant after seroconversion, yet pregnancy does not appear to influence the rate of progression of HIV disease.
Excess mortality (EM) is a valid indicator of COVID-19's impact on public health. Several studies regarding the estimation of EM have been conducted in Italy, and some of them have shown conflicting values. We focused on three estimation models and compared their results with respect to the same target population, which allowed us to highlight their strengths and limitations.We selected three estimation models: model 1 (Maruotti et al.) is a Negative-Binomial GLMM with seasonal patterns; model 2 (Dorrucci et al.) is a Negative Binomial GLM epidemiological approach; and model 3 (Scortichini et al.) is a quasi-Poisson GLM time-series approach with temperature distributions. We extended the time windows of the original models until December 2021, computing various EM estimates to allow for comparisons.We compared the results with our benchmark, the ISS-ISTAT official estimates. Model 1 was the most consistent, model 2 was almost identical, and model 3 differed from the two. Model 1 was the most stable towards changes in the baseline years, while model 2 had a lower cross-validation RMSE.Presently, an unambiguous explanation of EM in Italy is not possible. We provide a range that we consider sound, given the high variability associated with the use of different models. However, all three models accurately represented the spatiotemporal trends of the pandemic waves in Italy.
Healthcare workers (HCWs) are the target population for vaccination against coronavirus disease (COVID-19) as they are at a high risk of exposure and transmission of pathogens to patients. Neutralizing antibodies developed after COVID-19 vaccination decline within few months of vaccination. Several factors, including age and sex, can affect the intensity, efficacy, and duration of immune response to vaccines. However, sex-specific analyses of humoral responses to COVID-19 vaccines are lacking. This study aimed to evaluate sex-based differences in anti-S/RBD (Receptor Binding Domain) responses at three different time points after the second dose of mRNA COVID-19 vaccine in HCWs in relation to age, and to investigate the role of sex hormones as potential markers of response. Anti-S/RBD levels after two doses of the mRNA vaccine were collected from 521 HCWs naïve to COVID-19, working at two Italian Clinical Centers. Multiple regression analysis was applied to evaluate the association between anti-S levels and sex, age, and plasma levels of sex hormones. Significantly higher anti-S/RBD response to the COVID-19 vaccination was found in female HCWs, and a significant and more abrupt decline in response with time was observed in women than that in men. A novel, positive association of testosterone plasma levels and higher anti-S levels in male HCWs was found, suggesting its potential role as sex specific marker in males. In conclusion, understanding the sex-based differences in humoral immune responses to vaccines may potentially improve vaccination strategies and optimize surveillance programs for HCWs.
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 (Ulml) increased by 10% annually (95% Cl: 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.
To assess the impact of the COVID-19 pandemic on all-cause mortality in Italy during the first wave of the epidemic, taking into consideration the geographical heterogeneity of the spread of COVID-19.This study is a retrospective, population-based cohort study using national statistics throughout Italy. Survival analysis was applied to data aggregated by day of death, age groups, sex, and Italian administrative units (107 provinces). We applied Cox models to estimate the relative hazards (RH) of excess mortality, comparing all-cause deaths in 2020 with the expected deaths from all causes in the same time period. The RH of excess deaths was estimated in areas with a high, moderate, and low spread of COVID-19. We reported the estimate also restricting the analysis to the period of March-April 2020 (first peak of the epidemic).The study population consisted of 57,204,501 individuals living in Italy as of January 1, 2020. The number of excess deaths was 36,445, which accounts for 13.4% of excess mortalities from all causes during January-May 2020 (i.e., RH = 1.134; 95% confidence interval (CI): 1.129-1.140). In the macro-area with a relatively higher spread of COVID-19 (i.e., incidence rate, IR): 450-1,610 cases per 100,000 residents), the RH of excess deaths was 1.375 (95% CI: 1.364-1.386). In the area with a relatively moderate spread of COVID-19 (i.e., IR: 150-449 cases) it was 1.049 (95% CI: 1.038-1.060). In the area with a relatively lower spread of COVID-19 (i.e., IR: 30-149 cases), it was 0.967 (95% CI: 0.959-0.976). Between March and April (peak months of the first wave of the epidemic in Italy), we estimated an excess mortality from all causes of 43.5%. The RH of all-cause mortality for increments of 500 cases per 100,000 residents was 1.352 (95% CI: 1.346-1.359), corresponding to an increase of about 35%.Our analysis, making use of a population-based cohort model, estimated all-cause excess mortality in Italy taking account of both time period and of COVID-19 geographical spread. The study highlights the importance of a temporal/geographic framework in analyzing the risk of COVID-19-epidemy related mortality.
Objectives: To determine whether rate of development of AIDS is affected by category of exposure to HIV and whether the more rapid development found in older subjects persists for each exposure category. Design: Longitudinal study of people with known date of seroconversion to HIV. Setting: 16 HIV treatment centres throughout Italy. Subjects: 1199 people infected with HIV through use of injected drugs, homosexual sex, or heterosexual sex. Main outcome measures: AIDS as defined by 1987 definition of Centers for Disease Control (including and excluding neoplasms) and by 1993 European definition. Results: 225 subjects (18.8%) progressed to AIDS (Centers for Disease Control 1987 definition) during median follow up of 5.8 years. Univariate analyses showed more rapid progression to AIDS for older subjects compared with younger subjects and for homosexual men compared with other exposure categories. The age effect was of similar size in each exposure category and in men and women. In a bivariate model with age and exposure categories simultaneously included as covariates, differences by exposure category disappeared for use of injected drugs and heterosexual sex compared with homosexual sex (relative hazards 1.02 (95% confidence interval 0.71 to 1.45) and 1.07 (0.70 to 1.64) respectively), while the age effect remained (relative hazard 1.55 (1.32 to 1.83) for 10 year increase in age). Analyses using the other definitions for AIDS did not appreciably change these results. Conclusions: There was no evidence of differences in rate of development of AIDS by exposure category, while there was a strong tendency for more rapid development in older subjects for all three groups. This supports the view that external cofactors do not play major role in AIDS pathogenesis but that age is of fundamental importance.
Key messages
Many studies have found an age effect on progression to AIDS, but it is not clear if this is due to specific AIDS defining diseases such as neoplasms and if it differs by exposure groups or by sex Our study of 1199 subjects with known date of seroconversion to HIV showed that older subjects progressed to AIDS more rapidly in all exposure groups considered, for both men and women, and for different definitions of AIDS After adjustment for age at seroconversion, there was no evidence of different rates of progression among subjects belonging to different exposure categories Behavioural cofactors do not seem to play a major role in AIDS pathogenesis but age is of fundamental importance in disease progression
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