Missed opportunities to prevent mother-to-child transmission of HIV in Italy.

OBJECTIVES: Vertical transmission of HIV can be effectively controlled through antenatal screening, antiretroviral treatment and the services provided during and after childbirth for mother and newborn. In Italy, the National Health Service guarantees universal access to prenatal care for all women, including women with HIV infection. Despite this, children are diagnosed with HIV infection every year. The aim of the study was to identify missed opportunities for prevention of mother-to-child transmission of HIV. METHODS: The Italian Register for HIV Infection in Children, which was started in 1985 and involves 106 hospitals throughout the country, collects data on all new cases of HIV infection in children. For this analysis, we reviewed the database for the period 2005 to 2015. RESULTS: We found 79 HIV-1-infected children newly diagnosed after birth in Italy. Thirty-two of the mothers were Italian. During the pregnancy, only 15 of 19 women with a known HIV diagnosis were treated with antiretroviral treatment, while, of 34 women who had received an HIV diagnosis before labour began, only 23 delivered by caesarean section and 17 received intrapartum prophylaxis. In 25 mothers, HIV infection was diagnosed during pregnancy or in the peripartum period. Thirty-one newborns received antiretroviral prophylaxis and 39 received infant formula. CONCLUSIONS: We found an unacceptable number of missed opportunities to prevent mother-to-child transmission (MCTC). Eliminating HIV MTCT is a universal World Health Organization goal. Elucidating organization failures in Italy over the past decade should help to improve early diagnosis and to reach the zero transmission target in newborns.

Effects and safety of delayed versus early umbilical cord clamping in newborns of HIV-infected mothers.

OBJECTIVE: To investigate the effect of a 2 minutes-delayed cord clamp (DCC) versus early cord clamp (ECC) on neonate haemoglobin concentration 24 hours and 1 month after birth, and assess the safety of DCC concerning the risk of HIV infection. DESIGN: Sixty-four mother-infant peers were enrolled. All mothers were on stable ARV therapy. Viral load, CD4+ count and blood haemoglobin (Hb) concentrations 24 hours before delivery were collected from all mothers and their infants. METHODS: All patients were enrolled at the Department of Paediatrics, AO FBF Sacco Hospital in Milan, and were followed until 18 months after birth. Women with haematological diseases and obstetrical complications were excluded. All of 64 mother and infants couples (32 ECC group and 32 DCC group) completed the study. ECC and DCC are defined as application of umbilical clamp within 30 seconds and 120 seconds after birth, respectively. RESULTS: Mean birth weight was significantly higher in the DCC compared with ECC group. Mean Hb levels at birth were significantly higher in DCC than in ECC group (p = .05): this difference persisted at 1 month of life. All newborns showed negative viral load. CONCLUSIONS: DCC 2 minutes after birth is proven to be a safe procedure, particularly beneficial in newborns from HIV mothers. The risk of anemia is significantly decreased at 24 hours after birth and persists at age of 1 month without any increased risk of neonatal jaundice or polycitemia.

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV-1 infection 2015: optimizing health in preparation for adult life.

The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long-term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first- and second-line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART 'pipeline' of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

HCV-HIV coinfected pregnant women: data from a multicentre study in Italy.

PURPOSE: To provide information about main pregnancy outcomes in HIV-HCV coinfected women and about the possible interactions between HIV and HCV in this particular population. METHODS: Data from a multicenter observational study of pregnant women with HIV, conducted in Italian University and Hospital Clinics between 2001 and 2015, were used. Eligibility criteria for analysis were HCV coinfection and at least one detectable plasma HCV-RNA viral load measured during pregnancy. Qualitative variables were compared using the Chi-square or the Fisher test and quantitative variables using the Mann-Whitney U test. The Spearman's coefficient was used to evaluate correlations between quantitative variables. RESULTS: Among 105 women with positive HCV-RNA, median HCV viral load was substantially identical at the three trimesters (5.68, 5.45, and 5.86 log IU/ml, respectively), and 85.7 % of the women had at least one HCV-RNA value >5 log IU/ml. Rate of preterm delivery was 28.6 % with HCV-RNA <5 log IU/ml and 43.2 % with HCV-RNA >5log (p = 0.309). Compared to women with term delivery, women with preterm delivery had higher median HCV-RNA levels (third trimester: 6.00 vs. 5.62 log IU/ml, p = 0.037). Third trimester HIV-RNA levels were below 50 copies/ml in 47.7 % of the cases. No cases of vertical HIV transmission occurred. Rate of HCV transmission was 9.0 % and occurred only with HCV-RNA levels >5 log IU/ml. CONCLUSIONS: Coinfection with HIV and HCV has relevant consequences in pregnancy: HIV coinfection is associated with high HCV-RNA levels that might favour HCV transmission, and HCV infection might further increase the risk of preterm delivery in women with HIV. HCV/HIV coinfected women should be considered a population at high risk of adverse outcomes.

Resource utilization and direct costs of pediatric HIV in Italy.

This multicenter, prospective, observational study assessed the global economic impact of HIV care in a large cohort of HIV-infected children and adolescents in Italy. Three pediatric departments of reference participated on a voluntary basis. Centers were asked to enroll all their children during the period April 2010-March 2011. At enrollment, a pediatrician completed a questionnaire for each patient, including the type of service at access (outpatient consultation or day hospital), laboratory tests, instrumental examinations, specialists' consultations, antiretroviral therapy and opportunistic illness prophylaxis. Eligible patients had a confirmed diagnosis of HIV infection caused by direct vertical maternal-fetal transmission, their age ranging from 0 to 24 years. Since patients routinely have quarterly check-ups in all three centers, we adopted a three-month time horizon. Health-care services were priced using outpatient and inpatient tariffs. Drug costs were calculated by multiplying the daily dose by the public price for each active ingredient. A total of 142 patients were enrolled. More than half the patients were female and the mean age was 14 years, with no significant differences by center. There were substantial differences in health-care management among the three centers, particularly as regards the type of access. One center enrolled the majority of its patients in day-hospital and prescribed a large number of clinical tests, while children accessed another center almost exclusively through outpatient consultation. Drug therapy was the main cost component and was very similar in all three centers. The day-hospital was the second highest cost component, much higher than outpatient consultation (including examinations), leading to significant differences between total costs per center. These findings suggest that a recommendation to the Italian National Health Service would be to use more outpatient consultation for patients' access in order to increase their efficiency in treating pediatric HIV infection.

Italian consensus statement on paediatric HIV infection.

The objective of this document is to identify and reinforce current recommendations concerning the management of HIV infection in infants and children in the context of good resource availability. All recommendations were graded according to the strength and quality of the evidence and were voted on by the 57 participants attending the first Italian Consensus on Paediatric HIV, held in Siracusa in 2008. Paediatricians and HIV/AIDS care specialists were requested to agree on different statements summarizing key issues in the management of paediatric HIV. The comprehensive approach on preventing mother-to-child transmission (PMTCT) has clearly reduced the number of children acquiring the infection in Italy. Although further reduction of MTCT should be attempted, efforts to personalize intervention to specific cases are now required in order to optimise the treatment and care of HIV-infected children. The prompt initiation of treatment and careful selection of first-line regimen, taking into consideration potency and tolerance, remain central. In addition, opportunistic infection prevention, adherence to treatment, and long-term psychosocial consequences are becoming increasingly relevant in the era of effective antiretroviral combination therapies (ART). The increasing proportion of infected children achieving adulthood highlights the need for multidisciplinary strategies to facilitate transition to adult care and maintain strategies specific to perinatally acquired HIV infection.

A dangerous freshwater contact.

An 8-year-old girl was presented to our department for persistent diarrhoea. A first diagnosis of tuberculosis, along with the result of the chest x-ray scan, had been posed some months before, after a holiday in Brazil, when she started presenting aspecific systemic and gastrointestinal symptoms. The girl was under specific antitubercular treatment when we first saw her. New diagnosis of schistosomiasis was posed by our laboratory tests. Treatment with praziquantel was started and complete resolution of clinical and radiological picture was observed.

Preparing for an influenza pandemic in Italy: resources and procedures in paediatric hospital units.

The World Health Organization (WHO) has stated that preparedness for effectively facing a major influenza epidemic should involve the training of physicians in the management of contagious diseases and upgrading hospital resources and procedures [1]. Children would be particularly vulnerable during an influenza pandemic and specific measures are needed to face the threat to them effectively. We performed a national survey to obtain information about the preparedness in facing a major influenza outbreak in Italian paediatric units. In Italy, paediatrics clinics are found in both paediatric wards and paediatric departments. Departments are more complex structures, containing several units with different specialisations and facilities. For this study, we interviewed heads of both departments and units. A structured questionnaire, including 30 items, was submitted to the heads of 150 paediatric hospital departments across the country. Responses were obtained from 123 units; 10% of these had rooms dedicated to infectious diseases, and 4% had experts in infectious diseases available and routinely applied procedures for preventing the spreading of acute infectious diseases. Only 8% of departments have paediatric intensive care facilities. Few paediatric units, usually located in large children's hospitals or in academic paediatric departments, have a sufficient degree of preparedness to face severe influenza pandemics. A structural improvement of the paediatric units and the use specific procedures are essential for effectively care for children hospitalised because of contagious diseases.

Renal safety of tenofovir in HIV-infected children: a prospective, 96-week longitudinal study.

BACKGROUND: The renal safety of tenofovir in HIV-infected children has not been well studied. In paediatrics, prediction of glomerular filtration rate (GFR) is usually obtained by the Schwartz equation; the Cockcroft-Gault equation is considered more appropriate in children aged >12 years, but can be misleading in younger children. The aims of this study were to assess renal safety and GFR changes as estimated by the Schwartz and Cockcroft-Gault equations in HIV-infected children treated with tenofovir for 96 weeks. METHODS: Several parameters of glomerular and tubular function were prospectively assessed (at baseline and at weeks 24, 48, 72 and 96) in 27 HIV-infected children (aged 4.9-18.0 years) receiving a tenofovir-containing antiretroviral regimen. GFR was estimated using Schwartz and Cockcroft-Gault equations in children younger and older than 12 years, respectively. RESULTS: No child experienced a grade 1 (> or =44 micromol/L) or higher increase in serum creatinine or a grade 1 (< or =0.71 mmol/L) or higher hypophosphataemia. Serum bicarbonate values were in the normal range for age at baseline. Mean serum creatinine, serum phosphorus and serum bicarbonate values remained unchanged. No child showed proteinuria, microalbuminuria or glycosuria at baseline or during the study period. The mean urinary protein/creatinine, albumin/creatinine, alpha(1)-microglobulin/creatinine and maximal tubular phosphate reabsorption (TmPO(4)/GFR) ratios remained unchanged. Up to week 96, no patient experienced a significant decrease in GFR, as estimated by the more appropriate formula for age. CONCLUSION: Through 96 weeks, we found no evidence of impaired glomerular or tubular renal function in tenofovir-treated HIV-infected children.

Adherence to antiretroviral therapy in children: a comparative evaluation of caregiver reports and physician judgement.

Adherence to antiretroviral (ART) therapy, as reported by children caregivers, was investigated and compared with physicians' estimates of adherence. Two parallel structured questionnaires were administered to caregivers of 129 HIV-infected children and to their physicians in seven different Italian reference centers. Doses omitted in the last four days were recorded. Perfect adherence (>95% of prescribed doses taken in the last four days before interview) was reported by caregivers of 103 (79%) children. Five children (5%) omitted one dose of any ART drug in four days and were considered adherent. Low (<95 but >80% of doses) and poor (<80% of doses) adherence were reported by 15 (12%) and six (5%) caregivers, respectively. Forty-eight children (37%) were judged to be non-adherent by their physicians, including 35 children who were receiving all the prescribed doses according to caregivers. The physicians identified eight out of the 21 non-adherent children as adherent. Non-adherence estimates by physicians closely correlated with poor clinical conditions. These data indicate that adherence is a major problem but there is a clear discrepancy between caregiver reports and physician judgement. The results underline the need of close surveillance of adherence in HIV-positive children in order to evaluate the effectiveness of ART therapy.

Analysis of bone mineral content in horizontally HIV-infected children naïve to antiretroviral treatment.

Low bone mass is a frequent finding in HIV-infected individuals. Reduced bone mass has been found in vertically infected children who are receiving antiretroviral treatment. Little is known about bone mass in horizontally infected young patients who are naïve to antiretroviral therapy. We measured the bone mineral content (BMC) at the lumbar spine and in the whole skeleton by using dual-energy X-ray absorptiometry (DXA) in 16 HIV-infected children (age 9.3 +/- 3.9 years) naïve to antiretroviral treatment, and in 119 healthy children (age 9.7 +/- 3.3 years). Thirteen patients were also pair-matched by anthropometric measures, sex, and age with healthy children. Median spine BMC of HIV-infected children was 14.9 g (8.2-39.2 g), and whole body BMC was 1106.1 g (55.5-2344.1 g). Spine BMC of healthy children was 18.6 g (6.8-52.2 g), and whole body BMC was 1213.5 g (541.0-2722.0 g). Multivariate analysis showed a mean difference of spine BMC values of 0.004 g (P = 0.64) between the two groups. Similarly, the whole body BMC difference between the two groups (0.001 g) was not statistically significant (P = 0.55). Mean spine BMC measurements in the case-control evaluation were 21.1 g (9.7 g) (patients), and 22.3 g (6.9 g) (controls). Whole body BMC measurements of patients and controls were 1258.5 g (539.6 g) and 1311.1 g (479.2 g), respectively. In both cases the differences were not significant. The duration of HIV infection did not relate to BMC values. In conclusion, horizontally HIV-infected children naïve to antiretroviral therapy have bone mineral measurements comparable to those of healthy children.

Adherence to antiretroviral therapy and its determinants in children with human immunodeficiency virus infection: a multicentre, national study.

AIM: To investigate rates and determinants of adherence to antiretroviral therapy in Italian children infected with the human immunodeficiency virus (HIV). METHODS: An observational, cross-sectional multicentre study was performed through a structured interview with the caregivers of HIV-infected children. The interview included quantitative information on adherence in the 4 d before interview. Sociodemographic, clinical and psychosocial characteristics of children were recorded. RESULTS: 129 children (median age 96 mo) were enrolled, of whom 94 were on highly active antiretroviral therapy (HAART). Twenty-one (16%) omitted more than 5% of total doses in 4 d and were considered non-adherent. However, only 11% of caregivers reported that therapy had been administered at the correct times. No significant difference was found between age and the stage of HIV infection. Children aware of their HIV status were less adherent. Individual drugs showed a broad adherence pattern and children who received HAART were more adherent. Children receiving therapy from foster parents were more adherent than those receiving drugs from biological parents or relatives. CONCLUSIONS: Adherence is a major problem in children. Psychological rather than clinical or sociodemographic features and types of drug are major determinants of adherence.

Puberty in perinatal HIV-1 infection: a multicentre longitudinal study of 212 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.

Vulvar carcinoma in a 12-year-old girl with vertically acquired human immunodeficiency virus infection.

We report the first case of a girl with vertically acquired human immunodeficiency virus (HIV) infection, who developed invasive squamous cell carcinoma of the vulva at 12 years of age. Lesions resembling bowenoid papulosis covered the perianal area as well. She underwent a nonmutilating surgical excision of the infiltrating lesion. More than 3 years later, her clinical condition is excellent, although dysplastic, noninfiltrating multifocal lesions persist. This case highlights the need to perform careful periodic genital examinations in all HIV-infected children and adolescents born to HIV-positive mothers.

HIV: mother to child transmission, current knowledge and on-going studies.

It is estimated that approximately 6000 women of childbearing age, mostly living in the developing world, acquire HIV infection every day. Taking into account that approximately 98% of HIV infected children have acquired HIV from the mother, during pregnancy, at delivery or through breastfeeding, therefore, prevention of mother-to-child transmission (MTCT) is a major health priority. Several studies have showed how MTCT of HIV may be prevented using antiretrovirals. Results from a study conducted in Thailand have also recently showed how a short oral zidovudine course during pregnancy and labor may reduce the risk of HIV transmission by approximately 50%. These findings represent a major challenge for the International Health Agencies and Organizations that will have the major obligation to provide HIV tests, counseling and antiviral drugs in settings with high HIV prevalence.