Type I spinal muscular atrophy patients treated with nusinersen: 4-year follow-up of motor, respiratory and bulbar function.

BACKGROUND: We report the 4-year follow-up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number. METHODS: The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE-II). RESULTS: Forty-eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE-II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2-4 years, 5-11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE-2 increased significantly in patients younger than 2 years at treatment. In a mixed-model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not. CONCLUSIONS: Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time.

Needleless inhaled anesthesia with sevoflurane: Advantages of a simplified approach for children with spinal muscular atrophy undergoing intrathecal administration of nusinersen.

BACKGROUND: Intrathecal nusinersen administration, a fundamental step in the treatment of spinal muscular atrophy, is challenging in children. AIMS: This retrospective monocentric analysis of prospectively collected data evaluated the feasibility of needleless general anesthesia exclusively with sevoflurane, without imaging guidance, for children undergoing nusinersen administration in a 24-month period. METHODS: Clinical data included demographics, type of spinal muscular atrophy, presence and severity of scoliosis. Primary outcome was defined by the number of predefined sentinel adverse events related to anesthesia. Secondary outcomes were assessed by duration of the procedure, number of lumbar puncture attempts, and number of failures. Other measures included number and type of moderate, minor and minimal adverse events, as well as number and type of puncture-related adverse events. RESULTS: 116 patients (mean age: 8.7 (SD 6.9) years; with scoliosis: 49.1%) underwent 250 lumbar punctures; two cases of prolonged desaturation, considered as sentinel adverse events, (0.8%) were recorded during anesthesia (primary outcome). None of the patients underwent orotracheal intubation nor required an unplanned admission in the Pediatric Intensive Care Unit. No patient required an unplanned or prolonged hospitalization after the procedure. Mean number of puncture attempts was 1.6 (SD 1.3), and mean duration of the procedure was 14.1 (SD 8.3) minutes. No failure in the drug administration occurred (secondary outcomes). CONCLUSION: In this single-center experience, needleless general anesthesia with inhaled sevoflurane without imaging guidance has been shown to be feasible for children with spinal muscular atrophy undergoing lumbar puncture for nusinersen administration.

Noninvasive Ventilation in a Pediatric Trauma Center: A Cohort Study.

OBJECTIVE: To determine whether non-invasive ventilation (NIV) can avoid the need for tracheal intubation and/or reduce the duration of invasive ventilation (IMV) in previously intubated patients admitted to the pediatric intensive care unit (PICU) and developing acute hypoxemic respiratory failure (AHRF) after major traumatic injury. STUDY DESIGN: A single center observational cohort study. SETTING: Pediatric ICU in a University Hospital (tertiary referral Pediatric Trauma Centre). POPULATION: During the 48-month study period, 276 patients (median age 6.4 years) with trauma were admitted to PICU; among 86 of them, who suffered from AHRF and received ventilation (IMV and/or NIV) for more than 12 hrs, 32 patients (median age 8.5 years) were treated with NIV. INCLUSION/EXCLUSION CRITERIA: Inclusion criteria: at least 12 hours of NIV; exclusion criteria: patients with facial trauma or congenital malformations; patients receiving IMV <12 hours or perioperative ventilation. MEASUREMENTS AND RESULTS: Among NIV patients, 27 (84,3%) were previously on IMV, while 5 (15,6%) could be managed exclusively with NIV. In patients with post-extubation respiratory distress, NIV was successful in 88.4% of cases. Before starting NIV, P/F ratio was 242.7 ± 71. After 8 hours of NIV treatment, a significant oxygenation improvement (PaO2/FiO2 = 354.3 ± 81; p = 0.0002) was found, with no significant changes in carbon dioxide levels. A trend toward increasing ventilation-free time has been evidenced; NIV resulted feasible and generally well tolerated. CONCLUSIONS: AHRF in trauma patients is multifactorial and may be due to many reasons, such as lung contusion, aspiration of blood or gastric contents. Systemic inflammatory response and transfusions may also contribute to hypoxia. Our pilot study strongly suggests that NIV can be applied in post-traumatic AHRF: it may successfully reduce the time of both invasive ventilation and deep sedation. Further data from controlled studies are needed to assess the advantage of NIV in pediatric trauma.

Nusinersen in type 1 spinal muscular atrophy: Twelve-month real-world data.

OBJECTIVE: The aim of the study was to report 12-month changes after treatment with nusinersen in a cohort of 85 type I spinal muscular atrophy patients of ages ranging from 2 months to 15 years and 11 months. METHODS: All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination-Section 2 (HINE-2). RESULTS: Two of the 85 patients had 1 SMN2 copy, 61 had 2 copies, and 18 had 3 copies. In 4 patients the SMN2 copy number was not available. At baseline, the mean CHOP INTEND scores ranged between 0 and 52 (mean = 15.66, standard deviation [SD] = ±13.48), and the mean HINE-2 score was between 0 and 5 (mean = 0.69, SD = ±1.23). There was a difference between baseline and the 12-month scores on both the CHOP INTEND and the HINE-2 for the whole group (p < 0.001), the subgroups with 2 SMN2 copies (p < 0.001), and those with 3 SMN2 copies (p < 0.001). The difference was found not only in patients younger than 210 days at baseline (p < 0.001) but also in those younger than 5 years on the CHOP INTEND and younger than 2 years on the HINE-2. INTERPRETATION: Our results, expanding the age range and the severity of type I patients treated with nusinersen over 1 year, provide additional data on the range of efficacy of the drug that will be helpful in making an informed decision on whether to start treatment in patients of different ages and severity. ANN NEUROL 2019;86:443-451.

Clinical Outcomes and Prognostic Factors for Spontaneous Intracerebral Hemorrhage in Pediatric ICU: A 12-Year Experience.

BACKGROUND: In the pediatric population, spontaneous intracerebral hemorrhage (sICH) is as common as ischemic stroke and accounts for significant mortality and morbidity. Differently from the ischemic stroke, there are few guidelines for directing management of sICH. This article aims to analyze both clinical outcomes and prognostic factors in order to produce tools for the design of prospective randomized studies addressed to implement treatment of pediatric sICH. METHODS: Twelve-year retrospective review of a single-center consecutivesICH pediatric cases admitted to the pediatric intensive care unit (PICU). Selected end points were survival, PICU stay, and dichotomized Glasgow Outcome Score (GOS), with recovery and moderate disability (GOS 4-5) classified as favorable outcome and vegetative state or severe disability (GOS 2-3) classified as unfavorable. RESULTS: Data of 107 children younger than 14 years admitted to our PICU due to sICH were analyzed. Overall PICU mortality was 24.2%. On multivariate analysis, the single factor markedly influencing survival was the presence of midline shift (P = .002). In PICU survivors, there were 42 GOS 2-3 and 39 GOS 4-5. A low Glasgow Coma Scale (GCS) on PICU admission was predictive of severe neurological impairment in survivors (P = .003). Intraventricular hemorrhage and infratentorial origin did not influence outcome in this series. CONCLUSION: The severity of presentation of sICH expressed by the midline shift and the GCS at PICU admission are significant prognostic factors for survival and neurological outcome. Some prognostic factors of the adult population have not been confirmed.

Management of Anaesthesia.

Surgical treatment of the craniovertebral junction (CVJ) requires excellent management by the anaesthetist. Patients undergoing this type of surgery have a wide range of concomitant diseases. Therefore, before proceeding to CVJ surgery, it is recommended to analyse the clinical aspects of the patient that could complicate the outcome of the surgical procedure.In this paper we aim to establish what constitutes the best surgical and anaesthesia management of these patients. We consider airway management, trying to identify the gold standard for the patient. We also consider the most appropriate intraoperative approach to guarantee the best management of the patient.

Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report.

BACKGROUND: Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI. METHODS: A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days). RESULTS: NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported. CONCLUSIONS: Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

The second generation of HIV-1 vertically exposed infants: a case series from the Italian Register for paediatric HIV infection.

BACKGROUND: In the Highly Active Antiretroviral Therapy (HAART) era, the prognosis of children perinatally infected with HIV-1 has significantly improved, so the number of perinatally-infected females entering child-bearing age and experiencing motherhood is increasing. METHODS: A description of the medical history and pregnancy outcomes of women with perinatal acquired HIV-1 infection enrolled in the Italian Register for HIV infection in Children. RESULTS: Twenty-three women had 29 pregnancies. They had started an antiretroviral therapy at a median of 7.7 years (interquartile range, IQR 2.3 - 11.4), and had experienced a median of 4 therapeutic regimens (IQR 2-6). Twenty women (87%) had taken zidovudine (AZT) before pregnancy, in 14 cases as a starting monotherapy. In 21 pregnancies a protease inhibitor-based regimen was used. At delivery, the median of CD4+ T lymphocytes was 450/µL (IQR 275-522), and no viral load was detectable in 15 cases (reported in 21 pregnancies). Twenty-eight children were delivered through caesarean section (median gestational age: 38 weeks, IQR 36-38, median birth weight: 2550 grams, IQR 2270 - 3000). Intravenous AZT was administered during delivery in 26 cases. All children received oral AZT (median: 42 days, IQR 31 - 42), with no adverse events reported. No child acquired HIV-1 infection. CONCLUSIONS: Despite a long history of maternal infection, multiple antiretroviral regimens and, perhaps, the development of drug-resistant viruses, the risk of mother-to-child transmission does not seem to have increased among the second-generation of HIV-1 exposed infants.

Anaesthesiological and intensive care management in craniovertebral junction surgery.

The main factors of modern perioperative care of the craniovertebral junction surgery include a comprehensive approach to the patients, including a thorough cardiorespiratory, neurophysiological, and metabolic assessment, intraoperative monitoring of spinal cord function, safe airway management, and judicious use of fluids and blood transfusions. Admission in PICU shortly after the CVJ surgery is mandatory to ensure haemodynamic and respiratory stability and to recognize postoperative complications. Anticipating complications in order to achieve an early treatment and adverse event prophylaxis can contribute to reduced morbidity and mortality and increased patients' safety. Multidisciplinary management of perioperative patient care and careful pain control is mandatory in order to improve the outcomes.

Safety and efficacy of propofol administered by paediatricians during procedural sedation in children.

AIM: The aim of this study was to determine the safety and the efficacy of paediatrician-administered propofol in children undergoing different painful procedures. METHODS: We conducted a retrospective study over a 12-year period in three Italian hospitals. A specific training protocol was developed in each institution to train paediatricians administering propofol for painful procedures. RESULTS: In this study, 36,516 procedural sedations were performed. Deep sedation was achieved in all patients. None of the children experienced severe side effects or prolonged hospitalisation. There were six calls to the emergency team (0.02%): three for prolonged laryngospasm, one for bleeding, one for intestinal perforation and one during lumbar puncture. Nineteen patients (0.05%) developed hypotension requiring saline solution administration, 128 children (0.4%) needed O2 ventilation by face mask, mainly during upper endoscopy, 78 (0.2%) patients experienced laryngospasm, and 15 (0.04%) had bronchospasm. There were no differences in the incidence of major complications among the three hospitals, while minor complications were higher in children undergoing gastroscopy. CONCLUSION: This multicentre study demonstrates the safety and the efficacy of paediatrician-administered propofol for procedural sedation in children and highlights the importance of appropriate training for paediatricians to increase the safety of this procedure in children.

Complicated Falciparum Malarial ARDS Requiring Noninvasive Support.

Severe plasmodium falciparum infection can induce respiratory distress and clinical ARDS in children, requiring intensive care admission and respiratory support. We present 3 cases of imported malarial acute respiratory distress syndrome requiring noninvasive ventilation in the pediatric intensive care unit, in the absence of any cerebral involvement. Radiological features and their relationship with severe hematological complications are also illustrated.

Retrospective Study on Staphylococcus aureus Resistance Profile and Antibiotic Use in a Pediatric Population.

The growing phenomenon of antibiotic resistance and the presence of limited data concerning the pediatric area prompted us to focus on Staphylococcus aureus infection in this study, its antibiotic resistance profile, and the therapeutic management of affected children. We conducted a retrospective study by collecting clinical data on infants and children with antibiogram-associated S. aureus infection. We enrolled 1210 patients with a mean age of 0.9 years. We analyzed the resistance patterns and found 61.5% resistance to oxacillin, 58.4% resistance to cephalosporins, 41.6% resistance to aminoglycosides, and 38.3% resistance to fluoroquinolones. Importantly, we found no resistance to glycopeptides, a key antibiotic for MRSA infections whose resistance is increasing worldwide. We also found that the main risk factors associated with antibiotic resistance are being aged between 0 and 28 days, the presence of devices, and comorbidities. Antibiotic resistance is a growing concern; knowing the resistance profiles makes it possible to better target the therapy; however, it is important to use antibiotics according to the principles of antibiotic stewardship to limit their spread.

Intrapartum use of zidovudine in a large cohort of pregnant women living with HIV in Italy.

BACKGROUND: Intravenous administration of zidovudine (ZDV) during labour is a key step for vertical HIV transmission (VT) prevention, but there is no evidence of benefit when maternal HIV-RNA at delivery is <50 copies/mL. The aim of this study is evaluating the appropriateness of intrapartum ZDV use in Italy. METHODS: Observational study including mother-infant pairs with perinatal HIV exposure during 2002-2019, enrolled in the Italian Register for HIV Infection in Children. Univariable and multivariable logistic regression were used to evaluate factors associated with VT. RESULTS: A total of 3,861 infants, born from 3,791 pregnancies were included. The frequency of ZDV use was 79.9%, 92.1%, 93.7% and 92.8% when HIV-RNA was not available, ≥400 copies, between 50 and 399 copies, and <50 copies/mL. Thirty-three out of 3861 (0.85%) infants were subsequently diagnosed with HIV, 25/3861 (0.6%) of them born to mothers receiving intrapartum ZDV, and 31 (93.9%) to mothers with HIV-RNA ≥50 copies/mL or not available. In women with HIV-RNA < 50 copies/mL, ART discontinuation during pregnancy was the strongest risk factor for VT (odds ratio, OR, 23.1, 95%CI 2.4-219.3), while a higher gestational age (OR 0.6, 95%CI 0.4-0.8) and PEP administration to the newborn (aOR 0.004, 95%CI <0.0001-0.4) were protective factors. Intrapartum ZDV administration did not influence the final outcome in this group. CONCLUSIONS: In ART era, more transmission events may occur in utero, limiting value of intrapartum ZDV, particularly for women with suppressed HIV-RNA load. More attention to the HIV-RNA testing of mothers before delivery may avoid unnecessary ZDV use.

Hematological effects of zidovudine prophylaxis in newborn infants with and without prenatal exposure to zidovudine.

Postnatal prophylaxis with oral zidovudine (ZDV) is associated with hematological effects. However, it is still unknown whether selection of non-ZDV-based regimens in pregnancy may reduce hematological toxicity associated with postnatal ZDV prophylaxis. The aim of this study was to define the hematological effects of ZDV prophylaxis in newborns with and without prenatal exposure to ZDV. Sixty-five newborns from mothers infected with HIV who, during pregnancy, received HAART regimens with (n:44) and without (n:21) ZDV were evaluated. Virological and hematological data were compared at birth and at 4 weeks and 6 months of life. Newborns with prenatal ZDV exposure had significantly worse hematological values at birth, with lower levels of hemoglobin (14.3 g/dl vs. 16.2 g/dl, P=0.001), red blood cell count (3.45 × 10(6) cells/mm(3) vs. 4.48 × 10(6) cells/mm(3), P<0.001), and hematocrit (41.0% vs. 46.8%, P<0.001), and higher values of mean corpuscular volume (119 fl vs. 103 fl, P<0.001). The start of ZDV prophylaxis determined significantly greater adverse hematological changes in newborns without prenatal ZDV exposure, and at 4 weeks and 6 months of life the two groups had substantially identical hematological values. The selection of non-ZDV-based regimens in pregnancy does not reduce the final hematological effects of postnatal ZDV at 4 weeks and at 6 months of life. However, two distinct pathways may be observed: newborns exposed prenatally to ZDV have worse hematological values at birth, while newborns without prenatal ZDV exposure have particularly marked postnatal effects. The distinct effects of these two pathways should be considered.

Neonatal Life-Threatening Nonoliguric Hyperkalemia Under Therapeutic Hypothermia.

To illustrate our experience with two cases of neonatal life-threatening hyperkalemia during therapeutic hypothermia (TH) despite a normal acid-base status, urine output, and preserved renal function. Clinical cases are presented from Pediatric Intensive Care Unit (PICU) admission to the onset of the hyperkalemia, with related complications and after resolution. Similar cases were not retrieved from a critical review of pertinent literature. Severe hyperkalemia pathophysiology and risk factors have been debated. Two full-term adequate for weight female neonates were admitted to PICU because of perinatal asphyxia who underwent TH. Prenatal history was completely uneventful, nor hereditary genetic conditions were reported; moreover, long-term follow-up ruled out any metabolic or renal disease. Despite an accurate evaluation of previous clinical series and literature on TH and perinatal asphyxia, these hyperkalemic episodes remain unexplained. The hypoxic-ischemic insult may affect multiple organs, mainly central nervous system, heart, lung, and kidneys; acute muscle breakdown and consequent rising of myoglobin may also have a precipitating role in acute kidney failure (AKF) and hyperkalemia. Electrolyte imbalance is a possible finding as a consequence of combined cell injury and AKF. In contrast, an isolated severe hyperkalemia is exceedingly rare in nonoliguric neonates.

Type I SMA "new natural history": long-term data in nusinersen-treated patients.

OBJECTIVE: The aim of this paper was to report the 2-year follow-up in type I patients treated with Nusinersen and to assess whether possible changes in motor function are related to the subtype, age, or SMN2 copy number. METHODS: Sixty-eight patients, with ages ranging from 0.20 to 15.92 years (mean: 3.96; standard deviation: +3.90) were enrolled in the study. All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the developmental section of the Hammersmith Infant Neurological Examination (HINE-2) at the time they started treatment and 12 and 24 months after that. RESULTS: For both CHOP and HINE-2 repeated measures analysis of variance showed a significant difference (P < 0.001) between baseline and 12 months, 12 months and 24 months, and baseline and 24-month scores for the whole group. When age subgroups (<210 days, <2 years, 2-4 years, 5-11 years, 12-18 years) were considered, on the CHOP INTEND the difference was significant between baseline and 24 months in all age subgroups. On the HINE-2, the difference between baseline and 24 months was significant in all the subgroups before the age of 4 years. Age was predictive of changes on both scales (P < 0.05), whereas SMN2 copy number and decimal classification were not. INTERPRETATION: Our results suggest that some improvement of motor function can be observed even after the first year of treatment. This is more obvious in the infants treated in the first 2 years but some improvement can also be found in older children.

Spinal cord demyelination in children: A diagnostic challenge in neuropaediatrics for a good outcome.

BACKGROUND: Biotinidase deficiency (BTD) is an autosomal recessive inborn error of metabolism provoking progressive biotin depletion, which causes, in turn, multiple carboxylase deficiency. Its infantile onset is characterized by intractable seizures associated with lethargy, psychomotor regression, hypotonia, feeding and respiratory problems, and cutaneous abnormalities. CASE DESCRIPTION: We describe a 52-month-old female whose clinical and neuroradiological pictures were consistent with myelopathy, which is generally more frequent in older patients, as well as with symptoms of an infantile onset of biotinidase deficiency, revealed at 17 months. RESULTS: A biochemical biotinidase test revealed a profound deficiency of biotinidase detecting a 10% residual enzymatic activity, which led to the diagnosis of BTD. Gene sequencing revealed a compound heterozigous mutation (c.454A > C/c.1612C > T). CONCLUSION: Our findings suggest that even if myelopathy is uncommonly reported in BTD, and generally occurs in older children, its presence in childhood-onset floppiness should always be considered as a possible marker for an atypical presentation of BTD. Although, until recently, BTD myelopathy was believed to be prevalent in older children, a spinal cord involvement has also been described in at least nine cases in early infancy. Thus, another early diagnosis suggests that myelopathy may be more frequent than previously thought, and it is probably underdiagnosed because spinal MRI is not always routinely performed on these children. Early recognition of BTD disease is important as it would lead to prompt treatment, preventing irreversible brain damage and increasing the chances of complete recovery.

Is the interruption of antiretroviral treatment during pregnancy an additional major risk factor for mother-to-child transmission of HIV type 1?

BACKGROUND: 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. METHODS: 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. RESULTS: 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 delivery >4.78 log(10) copies/mL were independently associated with an increased rate of mother-to-child transmission. CONCLUSIONS: 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.

Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy.

BACKGROUND: Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking. METHODS: We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]:4.21-7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided. RESULTS: Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71-5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4+ T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4+ T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001). CONCLUSION: Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed.