Search

Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

Objective: To evaluate the effect of combined antiretroviral therapy on serum immunoglobulin (Ig) levels in HIV-1 perinatally infected children.Methods: Data from 1250 children recorded by the Italian Register for HIV Infection in Children from 1985 to 2002 were analysed. Since Ig levels physiologically vary with age, differences at different age periods were evaluated as differences in z-scores calculated using means and standard deviations of normal population for each age period. Combined antiretroviral therapy has become widespread in Italy since 1996, thus differences in Ig z-scores between the periods 1985-1995 and 1996-2002 were analysed. Data according to type of therapeutic regimen were also analysed.Results: Between the two periods 1985-1995 and 1996-2002, significant (P < 0.0001) decreases in IgG (6.29 +/- 4.72 versus 4.44 +/- 4.33), IgM (9.25 +/- 13.32 versus 5.61 +/- 7.93), and IgA (10.25 +/- 15.68 versus 6.48 +/- 11.56) z-scores, together with a parallel significant (P < 0.0001) increase in CD4 T-lymphocyte percentages, were found. These decreases were confirmed regardless of whether the children were receiving intravenous Ig or not. Ig z-scores were significantly higher in children receiving mono-therapy than in those receiving double-combined therapy (IgG, P < 0.0001; IgM, P = 0.003; IgA, P = 0.031) and in the latter children than in those receiving three or more drugs (P < 0.0001 for all z-scores). Ig z-scores correlated inversely with CD4 T lymphocyte percentages and, directly, with viral loads.Conclusions: Our data show that in HIV-1 infected children combined antiretroviral therapy leads to reduction of hyperimmunoglobulinemia which parallels restoration of CD4 T-lymphocyte percentage and viral load decrease, which it turn probably reflects improved B-lymphocyte functions.(C) 2004 Lippincott Williams Wilkins.

PURPOSE: We analyzed whether the prognosis can differ among Wilms tumors (WT) labeled as Stage III according to currently adopted classification systems. METHODS AND MATERIALS: Patients with nonanaplastic Stage III WT consecutively registered in two Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) trials (CNR-92, TW-2003) were the subjects in the present analysis. The steady mainstay of therapy was primary nephrectomy, followed by three-drug chemotherapy with vincristine, dactinomycin, doxorubicin, and abdominal radiotherapy (RT). RESULTS: Ninety-nine WT patients met the criteria for classification as Stage III according to a revised version of the National Wilms Tumor Study-3 staging system (51 patients in CNR-92, 48 patients in TW-2003). Regional lymph nodes (LN) were not biopsied in 16 patients. After a median follow-up of 66 months, the 4-year disease-free survival (DFS) and overall survival (OS) rates were 85% ± 4% and 92% ± 3%, respectively, for the whole group. For 38 children with positive LN, the 4-year DFS rate was 73% ± 7%, as opposed to 98% ± 2% for the 45 children with Stage III WT according to the other criteria but with negative biopsied LN (p = 0.001). The subgroup with the worst prognosis consisted of children more than 2 years old with positive LN (DFS 67% ± 8%). A delay between surgery and RT > 30 days had an adverse impact on the abdominal tumor relapse rate. CONCLUSIONS: This study provides further evidence that Stage III tumors with LN metastases might be distinguished from WTs meeting the other criteria for classification as Stage III. The worse outcome of the former may warrant a prospective study on the effects of intensified therapy. A subclassification of Stage III tumors is discussed.

Objectives To evaluate in a retrospective analysis the efficacy and safety of a 6 day course of liposomal amphotericin B (L-AmB) in infantile cases of Mediterranean visceral leishmaniasis (VL) diagnosed over a 10 year period in Italy. Patients and methods Patients included were diagnosed as having VL consecutively admitted from December 1992 to December 2001 at four main referral children's hospitals in Italy and treated with six intravenous doses of 3 mg/kg L-AmB given on days 1-5 and 10 (a total dose of 18 mg/kg). Demographic data, nutritional status, underlying diseases, clinical and laboratory findings, and therapy outcome were considered. Results A total of 164 HIV-negative children (median age 1.6 years; range 4 months to 14 years) were enrolled. All patients were initially cured by the given treatment, and did not present adverse events related to drug infusion. Seven patients (4.3%) had a clinical and parasitological relapse 3-15 months after therapy. All relapses were successfully retreated with 3 mg/kg L-AmB for 10 consecutive days (a total dose of 30 mg/kg). Conclusions This study highlights the efficacy (>95%) and safety of the six dose L-AmB regimen and validates it as a first-line treatment for Mediterranean VL in children.

OBJECTIVE: To define age at entry into Tanner stages in children with perinatal HIV-1 infection. DESIGN: Multicentre longitudinal study including 212 perinatally HIV-1-infected children (107 girls and 105 boys) followed-up during puberty (from 8 and 9 years onwards in girls and boys, respectively). Healthy children (843 girls and 821 boys) provided reference percentiles. P2 or B2 stages in girls and P2 or G2 stages in boys defined onset of puberty. METHODS: The cumulative probability [95% confidence limit (CI)] of entry into each stage at different ages was estimated by the Kaplan-Meier product-limit method; differences were evaluated by log rank test. Relationships were tested using the Spearman's rank correlation coefficient. RESULTS: Ages of girls [years (95%CI)] at P2 [12.9 (12.6-13.2)], P3 [13.4 (13.0-13.8)], P4 [14.6 (14.0-15.2)], B2 [12.7 (12.2-13.2)], B3 [13.3 (12.8-14.0)] and B4 [14.6 (14.0-15.2)] stages were > 97th percentile (> or = 21 month delay) of controls. Ages of boys [years (95%CI)] at P2 [12.6 (12.1-13.1)], P3 [13.9 (13.4-14.4)], P4 [14.9 (14.2-15.6)], G2 [12.1 (11.5-12.7)], G3 [13.6 (13.1-14.1)] and G4 [14.9 (14.1-15.7)] stages were at the 75-97th percentiles (< or = 15 month delay). Age at onset of puberty was not related to clinical and immunological condition, antiretroviral treatment, weigh for height and age at onset of severe disease or immune suppression. CONCLUSION: Perinatal HIV-1 infection interferes with sexual maturation. The mechanisms by which this occurs should be elucidated and intervention strategies designed. Intervention could save much psychological distress, since associated linear growth failure can exacerbate adolescents' feelings of being different and unwell.

There is currently an experts' agreement discouraging interruption of antiretroviral treatment (ART) during the first trimester of pregnancy in women infected with human immunodeficiency virus type 1 (HIV-1). However, this recommendation is poorly supported by data. We evaluated the effects of discontinuing ART during pregnancy on the rate of mother-to-child transmission.Logistic regression models were performed in a prospective cohort of 937 children who were perinatally exposed to HIV-1 to estimate adjusted odds ratios for confounding factors on mother-to-child transmission, including maternal interruption of ART.Among 937 pregnant women infected with HIV-1, ART was interrupted in 81 (8.6%) in the first trimester and in 11 (1.2%) in the third trimester. In the first trimester, the median time at suspension of ART was 6 weeks (interquartile range [IQR], 5-6 weeks) and the time without treatment was 8 weeks (IQR, 7-11 weeks). In the third trimester, the median time at suspension of ART was 32 weeks (IQR, 23-36 weeks) and the time without treatment was 6 weeks (IQR, 2-9 weeks). The plasma viral load was similar in women who had treatment interrupted in the first trimester and in those who did not have treatment interrupted. Overall, the rate of mother-to-child transmission in the whole cohort was 1.3% (95% confidence interval [CI], 0.7%-2.3%), whereas it was 4.9% (95% CI, 1.9%-13.2%) when ART was interrupted in the first trimester and 18.2% (95% CI, 4.5%-72.7%) when ART was interrupted in the third trimester. In the multiple logistic regression models, only interruption of ART during either the first or the third trimester, maternal mono- or double therapy, delivery by a mode other than elective cesarean delivery, and a viral load at delivery4.78 log(10) copies/mL were independently associated with an increased rate of mother-to-child transmission.Discontinuing ART during pregnancy increases the rate of mother-to-child transmission of HIV-1, either when ART is stopped in the first trimester and subsequently restarted or when it is interrupted in the third trimester. This finding supports recommendations to continue ART in pregnant women who are already receiving treatment for their health.

Purpose To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. Patients and Methods An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. Results Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). Conclusion Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.

Objective: To investigate the impact of early versus deferred combined antiretroviral treatment (ART) in asymptomatic or moderately symptomatic [Centers for Disease Control and Prevention (CDC) category N, A or B] infants with perinatal HIV-1 infection. Methods: A multi-centre nationwide case-control study was conducted. Data from 30 infants treated with combined ART with three or more drugs before 6 months of age were compared with data from 103 infants starting ART with three or more drugs after 6 months of age. The median follow-up time was 4.1 years (range, 1.0-6.5 years). Results: No difference was evident in the first available viral load and CD4 T-lymphocyte percentage between the two groups of children. Early-treated infants showed significantly lower viral loads than infants receiving deferred treatment at all the follow-up periods. A higher proportion of early-treated infants than infants receiving deferred treatment (73.3% versus 30.1%; P < 0.0001) reached an undetectable viral load. Higher CD4 T-lymphocyte percentages were found in early-treated infants at 13-24 (P < 0.0001), 25-36 (P < 0.0001), and 37-48 (P = 0.003) months of age. No early-treated infant versus 20 of 103 (19.4%) infants receiving deferred ART (P=0.02) showed a CD4 T-lymphocyte percentage of less than 15% at one time point during follow-up. No CDC category A, B or C clinical event occurred in early-treated infants over the follow-up period while 44 of 103 (42.7%) infants receiving deferred treatment presented a decline in the CDC category. Kaplan-Meier analyses revealed significant differences in CDC category A (P = 0.0002), B (P = 0.0003), and C (P = 0.0018) event-free survivals. Conclusion: The data suggest virologic, immunologic, and clinical benefits from early administration of ART.

The time at which antiretroviral therapy (ART) should be initiated in children with perinatal human immunodeficiencyvirus (HIV) infection remains controversial. In a cohort study, Berk et al1 reported clinical benefit from mono/dual ART started before 60 days of life in 10 children compared with treatment administered at 61 to 120 days of life in 16 children. The 23 children who received early triple ART were not investigated because none of them progressed to category C diagnosis by 3 years of age. We performed a similar analysis in a cohort study of a larger data set of children with a longer follow-up to evaluate the outcomes of early and very early triple ART.

Summary Non-expensive and low-complexity surrogate markers for monitoring the response to combined antiretroviral therapy (combined-ART) are needed in poor-resource settings where routine assessment of CD4+ T-lymphocyte count and viral load can not be afforded. We longitudinally evaluated Ig serum levels in 234 HIV-1 infected children receiving combined-ART with ≥ 3 drugs. Since Ig levels physiologically vary with age, differences at different age periods were evaluated as differences in z-scores calculated using the mean and standard deviation of the normal population for each age period. Data from 17 (7·3%) children with immunological failure and from 54 (23·1%) children with virological failure of combined-ART were compared with data from not-failed children. At baseline children with immunological failure showed higher IgM z-scores (P = 0·042) than children without. After 3–12 months of therapy immunologically failed children displayed higher viral loads (P < 0·0001) and IgA (P = 0·043) z-scores than not-failed children. Similarly, at the same follow-up time, children with virological failure showed lower CD4+ T-lymphocyte percentages (P = 0·005) and higher IgA z-scores (P < 0·0001) than not-failed children. No difference in IgG or IgM z-scores was evidenced between failed and not-failed children after 3–12 months of therapy. In conclusion, IgA serum level is a cheap and low-complexity marker of immunological or virological failure of combined-ART which might be adopted in poor-resource settings.

Objective: The Italian multicenter observational study depression in stroke (DESTRO) aimed to identify risk factors for poststroke depression (PSD) and quantify the likelihood of it arising in various categories of patients. Method: Mood evaluation was performed in 1064 consecutive stroke patients by means of Beck Depression Inventory and Visual Analog Mood Scale. Depressive symptoms were classified using the DSM-IV and revised WHO criteria for depression in the course of a neurological disorder. Results: Poststroke depression was seen in 36% of the survivors, with dysthymia by far the predominant form (80.7%). Female sex, disability, previous cerebrovascular or depressive episodes were significantly associated with an increased risk of depression. Combinations of these factors raised the risk of PSD exponentially, from 24.3 to 89.1%. The site of the stroke did not come into the uni- or multivariate analysis. Conclusion.: At admission, it is possible to predict the likelihood of PSD and quantify the relative risk.

Children with acquired immune deficiency syndrome (AIDS) commonly have recurrent infectious and noninfectious lung complications that ultimately end in death. To study the intensity of alveolar inflammation and to evaluate the clinical utility of bronchoalveolar lavage (BAL) in children with HIV-1 infections, we retrospectively analyzed differential cell counts, lymphocyte subsets, and fibronectin and hyaluronic acid concentrations in BAL fluid of 18 HIV-1-positive children (9 boys, mean age 3.5 years, range 5 months-8 years) with radiological evidence of interstitial lung disease, and 19 control children who had undergone BAL for clinical indications not involving the lung parenchyma (13 boys, mean age 3 years, range 2 months-14 years). BAL fluid from 89% of the HIV-1 infected children showed CD8+ve lymphocytic alveolitis expressing HLA-DR, CD54, and CD 69 antigens. BAL fluid from HIV-infected patients typically contained markedly increased percentages and numbers of lymphocytes (P < 0.0001) and eosinophils (P < 0.04) and significantly higher concentrations of albumin (P < 0.05) and fibronectin (P < 0.0006) than fluids from control children. Whereas BAL cellular components did not differ in P. carinii-positive and P. carinii-negative HIV-1-infected children, fibronectin concentrations were significantly higher in P. carinii-positive than negative children. BAL cell differentials and noncellular components were related neither to severity of disease nor to patients' disease progression. These findings indicate that BAL is useful in studying the intensity of lung inflammation in children with HIV-1 infections and radiologically documented interstitial lung disease, but provides no information on the subsequent clinical course.

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.

Nasopharyngeal swabs were collected from children aged 3–5 years in central Italy who were attending day-care centres or hospital outpatient clinics. One hundred and twenty-one strains of Streptococcus pneumoniae isolated were tested for susceptibility to penicillin, cefotaxime, erythromycin, clindamycin, tetracycline, chloramphenicol and cotrimoxazole. A high prevalence of penicillin-resistant (14%), erythromycin-resistant (60%) and multiply resistant strains (53%) were found. An unusual finding was that 49 of the 64 (76.6%) multiply resistant strains were penicillin-susceptible, 28 serogroup 6 strains also being resistant to the other antibiotics tested. Such strains have not previously been reported from Italy but have the same features as strains recently found in child carriers in the eastern Mediterranean area.

The innovative technologies of precision agriculture offer nowadays new applications in line with the needs of the wine sector. In hillside viticulture, within the same plot there are areas with different physical and chemical characteristics (lying, pH, active limestone, nutrients, etc.). This variability consequently influences the vigor of the vine which translates into a different production per single plant in terms of both yield and quality of the grapes. The aim of this study was to realize geo-referenced thematic maps by GPS application on a hilly plot covering about 6 hectares to be planted in a hedgerow trained vineyard for the production of quality grapes. The experimental tests were performed in the wine farm Tenute Rapitalà located in Camporeale (province of Palermo, Italy). STONEX S5 GPS was used for geo-referencing, with differential correction and sub-centimeter precision. Six thematic maps were created using GIS programs. The study allowed to obtain geo-referenced thematic maps with different classes of altitude, exposure, slope, pH, electrical conductivity, active limestone, total carbon and total nitrogen. The georeferenced maps have provided the possibility of defining rows orientation and length according to slope and exposure of the plot. This will reduce soil erosion to a minimum and maximize both soil fertility and plants photosynthetic activity.