Clinical outcomes in elderly patients with infections caused by NDM-producing Klebsiella pneumoniae: results from a real-life retrospective single center study in an endemic area.

Real-life outcomes data for elderly patients with infections caused by Klebsiella pneumoniae producing New Delhi metallo-beta-lactamase (NDM-Kp) are lacking. We conducted a retrospective cohort study enrolling 33 consecutive adult patients (mean age 77.4 years; 48.5% males; mean Charlson Comorbidity Index-CCI 5.9) hospitalized for NDM-Kp infections during a 24-month period in an Italian highly endemic area. 78.8% were admitted to Internal Medicine ward. 45.4% of patients had bloodstream infections (BSI), 39.4% urinary tract infections (UTI) without BSI, 9.1% respiratory tract infections and 6.1% intra-abdominal infections. 93.9% had rectal colonization.Adequate definitive antibiotic therapy (mainly represented by aztreonam plus ceftazidime/avibactam) was provided to 36.4% of cases. Mean age and CCI of patients adequately treated were significantly lower than those inadequately treated (71.2 vs 80.9 years, p = 0.041, and 4.6 vs 6.7, p = 0.040, respectively). Patients adequately treated had a mean hospitalization length significantly higher (28 vs 15 days, p = 0.016). The overall 30-day survival rate of patients adequately and inadequately treated was 83.3% and 57.1%, respectively: this difference was not statistically significant. Mean age and CCI of 22 patients who survived at 30 days were lower than those of 11 patients who died (73.7 vs 84.8 years, p = 0.003, and 5.3 vs 7.2, p = 0.049, respectively). Twelve survivors received an inadequate therapy: 8/12 had UTI. Six of nine patients inadequately treated who died within 30 days, died before microbiological diagnosis. Our study provides real-life data on outcomes of elderly and multimorbid patients hospitalized for infections caused by NDM-Kp. Further studies with larger sample size are warranted.

Primary septic arthritis of the knee caused by Neisseria meningitidis serogroup B in an elderly patient. Case report and review of the literature.

PURPOSE: Primary meningococcal arthritis (PMA) represents an uncommon clinical presentation of meningococcal infection, mainly reported among young people. Herein, a case of PMA of the knee in an elderly patient is described. CASE PRESENTATION: On January 2022, an 87-year-old patient arrived at hospital with continuous fever persisting for three days and a picture of pain, swelling, redness, and warmth of her left knee. An arthrocentesis was promptly performed and the inoculated synovial fluid turned positive with numerous Gram-negative diplococci at the microscopic examination. The identification of bacteria was done in 48 h using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) MS systems (VITEK®MS-bioMérieux) and standard microbiological procedures (VITEK®2 NH ID card-bioMérieux). Both methods identified the strain as N. meningitidis. The meningococcal isolate belonged to the serogroup B (MenB), Sequence type (ST)-162/clonal complex (cc)162. Two grams of ceftriaxone twice a day were administered for 21 days; than cefditoren pivoxil 400 mg twice a day for further 6 weeks after discharge. In Italy, from 2018 to January 2022, among 135 MenB, 31 MenB/cc162 were identified, of which only the case here reported was associated with an atypical clinical presentation. REVIEW OF THE LITERATURE: A total of 41 cases of PMA caused by N. meningitidis was reported in the literature, but only four occurred in elderly. To our knowledgements, no cases of PMA caused by MenB were previously reported among patients of more than 65 years of age.

Early 3-day course of remdesivir to prevent progression to severe Covid-19 in high-risk patients with hospital-acquired SARS-CoV-2 infection: preliminary results from two Italian outbreaks.

In multimorbid, unvaccinated and non-hospitalized patients, early administration of remdesivir, nirmatrelvir/ritonavir and molnupiravir was effective in reducing the risk of hospitalization or death from any cause. Similar data are lacking with regard to patients already hospitalized and who acquire in-hospital SARS-CoV-2 infection. We conducted a retrospective study during two outbreaks of SARS-CoV-2 infections involving 90 inpatients already hospitalized for medical or surgical conditions, in order to assess the effectiveness of early administration of remdesivir. Forty-seven cases were treated with a 3-day course of remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) within a median time of 1.4 day from testing positive, and were compared to a matched case-control cohort of 43 untreated patients; matching was based on age, sex, vaccination status, previous symptomatic infections by SARS-CoV-2, reasons for hospitalization (no significant differences). No case presented adverse events to remdesivir or death from COVID-19. No significant difference in overall in-hospital mortality was observed in cases compared to controls (17% vs 16.3%, p=0.925), but progression to severe pneumonia, although the difference was still not significant, showed an evident trend of a better outcome (8.5% vs 16.3%, p=0.261). Moreover, cases had a median discharge delay of 3 days (p=0.008).

Reinfection of SARS-CoV-2 - analysis of 23 cases from the literature.

INTRODUCTION: The duration of immunity after infection from SARS-CoV-2 conferring protection from subsequent COVID-19 episodes is not yet fully understood. We reviewed the literature for cases of documented reinfection. MATERIALS AND METHODS: A comprehensive computerized search in PubMed, through 15 December 2020, using the following terms in combination: COVID-19, SARS-CoV-2, reinfection, reactivation, recurrence. To exclude cases due to prolonged viral shedding or protracted infection, only cases occurring at least 12 weeks apart or confirmed as being sustained by genetically different viruses by viral genome analysis were included. RESULTS: We identified 23 cases globally, for which viral genome analysis was performed in 10 cases and serology in 19 cases. The mean interval between the two episodes was 15 weeks. Mean age of cases was 44.5 years, and 10 (43.5%) were women. In 17/23 cases, no comorbidity was observed. In 10 cases, the first episode was more severe than the ensuing episode, whereas in seven cases the ensuing episode was more severe. In four cases, there was no difference in severity and in two cases both episodes were asymptomatic. CONCLUSIONS: From this sample of 23 cases, a clear pattern of the second episode being less or more severe did not emerge. A better understanding of immunity to SARS-CoV-2, necessary to assess the probability of a second infection and the durability of protection conferred by vaccination, is warranted.

Validity of "Sepsis-3" criteria in identifying patients with community-onset sepsis in Internal Medicine wards; a prospective, multicenter study.

BACKGROUND: Few data are available on the validity of "Sepsis-3" criteria in identifying patients with sepsis in internal medicine wards (IMWs). Real-life data about this topic and on the prevalence of sepsis in IMWs could be useful for improving hospital organization. OBJECTIVES: To assess the validity of "Sepsis-3" criteria in identifying patients with community-onset sepsis in IMWs. Secondary objectives: to evaluate the prevalence of these patients in IMWs and to compare "Sepsis-3" and "Sepsis-1" criteria. METHODS: Multicenter, prospective, observational, cohort study, carried out in 22 IMWs of Tuscany (Italy). All patients admitted to each of the study centers over a period of 21-31 days were evaluated within 48 hours; those with clinical signs of infection were enrolled. The main outcome was in-hospital mortality. RESULTS: 2,839 patients were evaluated and 938 (33%) met the inclusion criteria. Patients with sepsis diagnosed according to "Sepsis-3" were 522, representing 55.6% of patients with infection and 18.4% of all patients hospitalized; they were older than those without sepsis (79.4±12.5 vs 74.6±15.2 years, p<0.001). In-hospital mortality was significantly higher in patients with sepsis compared to others (13.8% vs 4.6%; p<0.001). "Sepsis-3" criteria showed greater predictive validity for in-hospital mortality than "Sepsis-1" criteria (AUROC=0.71; 95%CI, 0.66-0.77 vs 0.60; 95%CI 0.54-0.66; p=0.0038). CONCLUSIONS: "Sepsis-3" criteria are able to identify patients with community-onset sepsis in IMWs, whose prevalence and in-hospital mortality are remarkably high. Medical departments should adapt their organization to the needs for care of these complex patients.

Role of Lopinavir/Ritonavir in the Treatment of Covid-19: A Review of Current Evidence, Guideline Recommendations, and Perspectives.

A life-threatening respiratory illness (COVID-19) due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus was first described in December 2019 in Wuhan (China), rapidly evolving into a pandemic. In the first phase, when the viral replication plays a pivotal pathogenetic role, antiviral drugs could be crucial in limiting viral-induced organ damage. Unfortunately, there are no specific antivirals of proven efficacy for COVID-19, and several drugs have been repurposed to face this dramatic pandemic. In this paper we review the studies evaluating lopinavir/ritonavir association (LPV/r) use in COVID-19, and previously in SARS and Middle East respiratory syndrome (MERS). We searched PubMed to identify all relevant clinical and laboratory studies published up to 15 May 2020; the guidelines on the use of LPV/r in COVID-19 were further directly searched on the website of the main international scientific societies and agencies. Available evidence is currently scarce and of low quality. The recommendations issued for COVID-19 vary from positions clearly against the use of LPV/r to other positions that are more favorable. In our opinion, despite the controversial results of an important randomized clinical trial, and some recommendations, clinicians should not abandon the use of LPV/r for the treatment of COVID-19, possibly using this drug inside a prospective randomized trial, waiting for the results of the numerous ongoing trials evaluating its efficacy.

Targeting candidates for directly administered highly active antiretroviral therapy: benefits observed in HIV-infected injecting drug users in residential drug-rehabilitation facilities.

The purpose of this study was to evaluate retrospectively the potential benefits of directly administered antiretroviral therapy (DAART) in HIV-infected former injecting drug users (ex-IDUs) admitted to residential drug rehabilitation facilities. We compared 106 of these patients consecutively admitted in 12 communities where DAART was administered (DAART group) to two matched control groups of ex-IDUs undergoing self-administered ART: 106 subjects in other 10 communities (SAT group) and 106 outpatients at hospital infectious-disease wards where community patients were referred after discharge (OUT group). We estimated the proportion of patients with high adherence and the hazard ratio (HR) of 20% or more increase in the CD4(+) cell count and of reaching an undetectable viral load. The proportion of patients with high adherence to treatment was highest in the DAART group. The probability of 20% or more increase in the CD4(+) cell count was significantly lower in the two control groups versus the DAART group (SAT group HR=0.32; OUT group HR=0.43). The HR of observing an undetectable HIV-RNA level versus DAART was significantly lower in the OUT group (HR: 0.71; 95% confidence interval [CI]: 0.52-0.97) but did not reach statistical significance for the SAT group (HR: 0.99; 95% CI: 0.74-1.33). Our findings after a 24-month follow-up, suggest that DAART in HIV-infected patients of drug-rehabilitation communities improves adherence, immunologic, and virologic outcome toward free outpatients. Even if our retrospective 36-month data do not show a prolonged viral suppression in these patients, DAART may be considered a valuable therapeutic and educational strategy in this particular target group.

Characteristics and behaviors in a sample of patients unaware of their infection until AIDS diagnosis in Italy: a cross-sectional study.

The objective of this study was to define the sociodemographic and behavioral characteristics of people unaware of being HIV-positive at AIDS diagnosis. A multi-center cross-sectional study was conducted in 11 Italian centers of infectious diseases, recruited on a voluntary basis. Each center enrolled individuals diagnosed with AIDS aged ≥ 18 years from May 2003 to December 2005. The patients were classified into two groups on the basis of the amount of time that elapsed from diagnosis of HIV infection to AIDS diagnosis. "Late testers" were defined as those with a time period of ≤ 6 months between first HIV positive test and AIDS diagnosis. In order to evaluate the factors independently associated with being a late tester, a multivariate logistic regression model was performed. The McNemar χ(2) test was used to analyze behavioral changes before and after HIV diagnosis. During the study period, 245 patients were enrolled; of these, 51.8% were late testers. The variables independently associated with being a late testers were as follows: being employed; having acquired the infection through sexual contacts; having taken the HIV test because they didn't feel well; having at least one symptom or illness among those indicating infection; and not having had paid sex within the 12 months prior to HIV diagnosis. Before and after HIV diagnosis a significant increase in safe-sex behaviors was observed among individuals with no delay in diagnosis. However, the proportion of people who continue not to use condoms is still high. This study seems to indicate that sexual transmission is often associated with late testing. Individuals enrolled seem to have a low perception of risk, they do not undergo HIV testing, and consequently miss the opportunity of early diagnosis.

Community-acquired pneumonia.

PURPOSE OF REVIEW: Community-acquired pneumonia (CAP) is a major cause of morbidity, mortality and expenditure of resources. When followed, guidelines for CAP management have been demonstrated to improve clinical outcomes; however, several issues are still open. This review summarizes the recent advances in this field and the priority needs for future research. RECENT FINDINGS: Recently identified clinical and biochemical tools promise to improve the assessment of CAP severity; however, definition of the most accurate and feasible rule(s) for clinical practice is now necessary. Some empirical antimicrobial regimens are still being debated, such as the need for atypical pathogen coverage in home-treated and nonsevere hospitalized patients and the inclusion of respiratory fluoroquinolones among first-choice molecules. New drugs such as tigecycline and cethromycin appear promising. Pharmacokinetically enhanced amoxicillin/clavulanate is highly effective, even for treating CAP caused by multiple-drug-resistant Streptococcus pneumoniae. Other aspects recently clarified include the inappropriateness of rigid time-to-first-antibiotic-dose rules, the advantages of shorter antibiotic treatments for nonsevere patients and the need of special clinical attention for acute myocardial infarction among patients with severe CAP or clinical failure. SUMMARY: Recent developments have significantly contributed to refine the management of CAP patients. However, various hot topics remain undefined as yet and urgently require ad-hoc research in order to optimize the outcomes and the costs of this highly social-impacting disease.

HIV-1 diversity among inmates of Italian prisons.

In Italy, the prevalence of non-B HIV-1 subtypes ranges reportedly from 5.4% to 12.6%, yet there are no data on their circulation in prisons, where the prevalence of HIV infection is high. A retrospective study was conducted to evaluate the circulation of non-B subtypes and to characterize their determinants in five Italian prisons. To this end an aliquot of samples of blood was taken in the period 2001-2006 from all 262 HIV-positive inmates in whom antiretroviral treatment had failed. Complete HIV-1 PR and RT regions were sequenced for all samples and subjected to phylogenetic analysis; 250 (95.4%) sequences clustered with subtype B. The non-B subtype was found in 4% of Italian prison inmates and 16.7% of non-Italian prison inmates; the overall percentage increased from 1.8% for inmates infected in 1982-1990 to 4.4% in 1991-1999 and 21.9% in 2000-2006. Factors significantly associated with non-B subtypes were an exposure to other than injecting drug use and a first positive HIV test in 2000-2006. Non-B subtypes were distributed within five monophyletic clades. In all cases but one, it was possible to correlate the history of HIV-exposure to the origin of the clade, with high bootstrap values. In conclusion, although the sample may not be representative of the prison inmate population in Italy, the data suggest strongly that the circulation of non-B subtypes has apparently increased. Non-B subtypes were found to have been associated with heterosexual contact and time of the first HIV-positive test. Knowledge of the different subtypes circulating in prisons may be useful for tracking the epidemiology of HIV infection and for choosing antiretroviral therapy.

Increasing proportion of AIDS diagnoses among older adults in Italy.

We evaluated the impact of AIDS among older persons in Italy and compared these cases with cases among younger persons. The data source was Italy's National AIDS Registry. We considered adults diagnosed with AIDS between 1982 and 2005. Older adults were defined as those aged 50 years or older at diagnosis. Of the total adult cases, 8.8% were among older adults. This proportion increased over time, from 4.9% in 1982-1990 to 15.9% in 2000-2005. Among older adults, the most represented exposure category (80.8%) was sexual intercourse (heterosexual and homosexual). At AIDS diagnosis, older adults, compared to younger adults, had a higher risk of developing AIDS dementia complex or wasting syndrome, and of presenting multiple AIDS-defining illnesses. A significantly lower proportion of older adults were undergoing antiretroviral therapy, compared to younger adults. Among older adults, 67.2% were late testers, compared to 32.8% of younger adults. Most of the older adults acquired the infection through sexual contact; approximately two thirds of them were diagnosed late (i.e., first HIV-positive test 6 months or less before AIDS diagnosis); and only one fourth were undergoing antiretroviral therapy at diagnosis. These observations stress the need to more seriously consider the possibility of HIV infection among older individuals and to collect more detailed information on their sexual behavior.

Molecular findings and antibiotic-resistance in an outbreak of Acinetobacter baumannii in an intensive care unit.

We investigated an outbreak of Acinetobacter baumannii in the intensive care unit (ICU) of a hospital in Rome, Italy. The outbreak involved 14 patients whose isolates were most frequently recovered from bronchoalveolar lavage. All isolates were multidrug-resistant and showed diminished susceptibility or resistance to carbapenems. A. baumannii strains with a similar antibiotic susceptibility pattern were isolated from the environment. Pulsed-field gel electrophoresis identified a single clone from both the patients' and environmental isolates. Because of the lack of a single source of infection, the eradication of the epidemic required a broad approach, including contact isolation and cohorting, aggressive environmental disinfection, and close monitoring of the ward staff's performance. Infected patients were successfully treated with combined therapy. Although considered of low virulence, A. baumannii can be particularly aggressive and difficult to treat in ICU patients.

[The HIV epidemiology in province of Modena: use of two different sources of data]. / L'utilizzo di due fonti di dati diverse nella descrizione dell'epidemia da HIV nella Provincia di Modena.

OBJECTIVE: to analyse demographic characteristics and risk factors of people living with HIV and to compare data from the surveillance system for new HIV diagnoses with those from the National AIDS Registry (RAIDS). DESIGN: comparison of two surveillance systems. SETTING: province of Modena. PARTICIPANTS: cases reported to the RAIDS and to the HIV surveillance system, from 1985 to 2004 regarding residents in the province of Modena. MAIN OUTCOMES: number of cases and incidence, by exposure categories, age, and gender. RESULTS: from 1985 to 2004, 615AIDS cases and 1731 new HIV diagnoses were reported among residence in the province of Modena. The incidence of AIDS progressively decreased after 1995, whereas incidence of new HIV diagnoses remained stable since 1994 with annual rates up to three-fold higher than those reported for the AIDS cases. Individuals with a new HIV diagnosis were younger (<30 years of age), with a higher proportion of females and heterosexuals compared to AIDS cases. The most represented age group among AIDS cases was 30-49 years whereas it was <30 years for newly diagnosed HIV cases. The proportion of intravenous drug users decreased over time both among new AIDS cases and new HIV diagnoses, whereas the proportion of cases attributed to sexual transmission increased. The proportion of foreigners among newly diagnosed HIV cases was twice as high as among AIDS cases. CONCLUSIONS: this study shows that, especially after the introduction of highly active antiretroviral therapies, information on AIDS cases has become less representative of the trends to HIV epidemic. Therefore, AIDS surveillance systems should be combined with local surveillance systems on new HIV diagnoses.

An outbreak of influenza in a residential drug-rehabilitation community.

Influenza outbreaks can be difficult to control in confined settings where high-risk individuals are concentrated. Following the occurrence of a large number of cases of influenza-like illness in a rehabilitation community for drug users, between February and March 2004, surveillance activities were implemented. Attack rates of influenza-like illness were calculated, and risk factors for the development of disease and complications were evaluated through the use of relative risks (RR) with 95% confidence intervals (CI). Nasal-pharyngeal samples were collected for virological studies. Of 1,310 persons who were living in the community, 209 were diagnosed with influenza-like illness: the attack rate (15.9% overall) was higher for HIV-infected persons (RR: 1.77, 95% CI: 1.32-2.37), older individuals, and dormitory residents. HIV-infected participants were also more likely to develop complications compared with HIV-uninfected persons diagnosed with influenza-like illness (RR: 5.13, 95% CI: 2.52-10.20). The outbreak was attributable to Christchurch-like influenza A strains. Vaccination was ineffective because of the mismatch between wild and vaccine strains.

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

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

Prevalence of transmitted HIV-1 drug resistance and the role of resistance algorithms: data from seroconverters in the CASCADE collaboration from 1987 to 2003.

OBJECTIVES: To examine factors influencing the rate of transmitted drug resistance (TDR) among seroconverters, with particular emphasis on 3 widely used genotypic drug resistance algorithms. METHODS: The study used data from CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe), a collaboration of seroconverter cohorts in Europe and Canada. Genotypic resistance data were derived within 18 months of the last seronegative test or date of laboratory evidence of acute infection and before the initiation of antiretroviral therapy. The Stanford algorithm was used to analyze each individual's nucleotide sequence. A multivariate logistic model was used to assess independent relationships between the presence of TDR and exposure category, sex, age at seroconversion, and year of seroconversion. The paper also describes 3 alternative definitions of resistance: the Stanford algorithm, the key resistance mutations defined by the International AIDS Society, and the Agence Nationale de Recherches sur le Sida (ANRS) algorithm. RESULTS: Forty-five of 438 patients (10.3%) seroconverting between 1987 and 2003 were infected with a drug-resistant HIV-1 variant. Forty patients (9.1%) showed resistance mutations to only 1 class of antiretroviral drugs, 2 (0.5%) to 2 classes, and 3 (0.7%) to 3 classes of antiretroviral therapy. It was suggested that individuals seroconverting later in calendar time were more likely to have TDR (relative risk 3.89 and 95% CI: 0.84 to 18.02, and relative risk 4.69 and 95% CI: 1.03 to 21.31, for 1996-1999 and 2000-2003, respectively, compared with pre-1996; P trend = 0.08). This trend was apparent regardless of the definition of TDR used. The total estimated proportion of individuals with TDR varied between 10.3% and 15.5% according to which definition was used. CONCLUSIONS: Evidence was found for the rise of TDR over time. A specific definition of what constitutes TDR rather than a simple list of mutations is needed.

Exanthematic diseases during pregnancy and attention-deficit/hyperactivity disorder (ADHD).

Rash causing viral diseases may be transmitted during pregnancy, causing severe congenital disease. Although neurological and psychiatric disorders are common consequences of congenital rubella, children born to women who developed a viral rash during pregnancy do not appear to be at increased risk of these disorders if they were asymptomatic at birth. In a case-control study conducted to evaluate risk factors for ADHD, we found an increased risk of this disorder among children born to women experiencing a viral rash during pregnancy. The viral rash (i.e. measles, varicella, or rubella) was reported by 4 of 71 mothers of children with ADHD and none of the 118 controls' mothers (P<0.01). The difference remained statistically significant after adjusting for potential confounders (i.e. other factors found associated with ADHD, such as gender and familiarity). Although, the viral disease reported by the mothers, in accordance with their physician's diagnosis, did not represent a homogeneous nosological group, the unexpectedly high rate found among ADHD cases' mothers suggest a role for viral diseases occurring during pregnancy in the development of ADHD.

Changes over time in post-seroconversion CD4 cell counts in the Italian HIV-Seroconversion Study: 1985-2002.

OBJECTIVE: To determine whether there has been a tendency for early post-seroconversion CD4 cell counts to change over calendar time. DESIGN: A prospective cohort study of individuals with well-estimated dates of seroconversion. METHODS: We studied 1251 individuals who seroconverted to HIV in Italy between 1985 and 2002, and for whom the first CD4 count was measured within 2 years of seroconversion and before any use of antiretrovirals. Linear regression models were used to assess evidence for a trend in post-seroconversion CD4 cell count over time. RESULTS: The median post-seroconversion CD4 cell count was 674 x 10 cells/l in those seroconverting between 1985 and 1990, 588 x 10 cells/l for 1991 to 1994, 559 x 10 cells/l for 1995 to 1998 and 494 x 10 cells/l for 1999 to 2002. The post-seroconversion CD4 cell count decreased by an average of 8.4 x 10 cells/l per year (95% confidence interval, 4.0-12.9; P < 0.001), after adjustment for potential confounders, including interval between HIV-negative and HIV-positive tests, lag time for first CD4 cell count measurement, age at seroconversion, gender, HIV-transmission group, and clinical centre. The finding was consistent in sensitivity analyses restricted to those with information on acute infection. CONCLUSION: These data suggest a possible decreasing trend in CD4 cell count immediately following seroconversion in Italy which requires further investigation.