A Cluster Randomised Controlled Trial of an Intervention to Increase Physical Activity of Preschool-Aged Children Attending Early Childhood Education and Care: Study Protocol for the 'Everybody Energise' Trial.

The use of 'Energisers,' short bouts of moderate-to-vigorous physical activity (MVPA), have been shown to significantly increase children's physical activity within the school setting but not within Early Childhood Education and Care (ECEC) centres. The aim of this study is to assess the efficacy of an intervention involving the provision of educator-led daily Energisers to increase the time children spend in MVPA while attending ECEC. Fourteen ECEC centres in the Hunter region of New South Wales, Australia, will be randomised to either an intervention or control group. The intervention group will be supported by the research team to implement three brief (5-min) educator-led Energisers each day for children aged three to six years between the hours of 9:00 a.m. to 3.00 p.m. Control ECEC centres will continue to provide 'normal practice' to children. The primary trial outcome is child minutes of MVPA whilst in ECEC, assessed objectively via accelerometery over three days. Outcome assessment will occur at baseline and 6 months post-baseline. Linear mixed models under an intention-to-treat framework will be used to compare differences between groups in MVPA at follow-up. This will be the first cluster randomised controlled trial to test the efficacy of Energisers in isolation on increasing the time children spend in MVPA.

Policy change eliminating body checking in non-elite ice hockey leads to a threefold reduction in injury and concussion risk in 11- and 12-year-old players.

BACKGROUND: In ice hockey, body checking is associated with an increased risk of injury. In 2011, provincial policy change disallowed body checking in non-elite Pee Wee (ages 11-12 years) leagues. OBJECTIVE: To compare the risk of injury and concussion between non-elite Pee Wee ice hockey players in leagues where body checking is permitted (2011-12 Alberta, Canada) and leagues where policy change disallowed body checking (2011-12 Ontario, Canada). METHOD: Non-elite Pee Wee players (lower 70%) from Alberta (n=590) and Ontario (n=281) and elite Pee Wee players (upper 30%) from Alberta (n=294) and Ontario (n=166) were recruited to participate in a cohort study. Baseline information, injury and exposure data was collected using validated injury surveillance. RESULTS: Based on multiple Poisson regression analyses (adjusted for clustering by team, exposure hours, year of play, history of injury/concussion, level of play, position and body checking attitude), the incidence rate ratio (IRR) associated with policy allowing body checking was 2.97 (95% CI 1.33 to 6.61) for all game injury and 2.83 (95% CI 1.09 to 7.31) for concussion. There were no differences between provinces in concussion [IRR=1.50 (95% CI 0.84 to 2.68)] or injury risk [IRR=1.22 (95% CI 0.69 to 2.16)] in elite levels of play where both provinces allowed body checking. CONCLUSIONS: The rate of injury and concussion were threefold greater in non-elite Pee Wee ice hockey players in leagues where body checking was permitted. The rate of injury and concussion did not differ between provinces in elite levels, where body checking was allowed.

Longitudinal Evaluation of Immune Reconstitution and B-cell Function After Hematopoietic Cell Transplantation for Primary Immunodeficiency.

PURPOSE: Hematopoietic cell transplantation (HCT) provides a curative therapy for severe forms of primary immunodeficiencies (PID). While the timing and extent of T-cell reconstitution following transplant for PID has been studied in depth, less is known about the kinetics of B-cell development and long-term restoration of humoral functions, which been often reported to be suboptimal after HCT. METHODS: We studied longitudinally B-cell development and function in a cohort of 13 PID patients transplanted between 1997 and 2010, with a follow-up ranging from 0.7 to 15 years. Flow cytometric analysis of naïve and antigen-experienced B-cell subsets and in vitro functional responses to CpG were compared with data from healthy children and correlated with the degree of B-cell chimerism and in vivo antibody production. RESULTS: We found that total memory B-cells count remained below normal levels for the first 2 years of follow up and progressively normalized. Switched memory B-cells (CD19+CD27+IgD-IgM-) were restored early and better than IgM memory B-cells (CD19+CD27+IgD+IgM+), which remained significantly reduced long-term. The recovery of memory B-cells correlated with good in vivo humoral function and normalization of CpG-response. A complete B-cell reconstitution was usually associated with donor B-cells chimerism and pre-transplant conditioning. Donor source and the underlying genetic defect represented also important variables. CONCLUSION: Monitoring of phenotypic and functional changes on B-cells following HCT may prove clinically relevant to tailor patients' care. In particular the analysis of IgM memory and switched memory B-cells in addition to in vitro B-cells stimulation are recommended before Ig replacement therapy (IgRT) discontinuation.

The effect of coach and player injury knowledge, attitudes and beliefs on adherence to the FIFA 11+ programme in female youth soccer.

BACKGROUND: Injury knowledge and beliefs influence uptake of prevention programmes, but the relationship between knowledge, beliefs and adherence remains unclear. AIM: To describe injury knowledge and beliefs among youth female soccer coaches and players, and to identify the relationship between these factors, different delivery strategies of the FIFA 11+ programme and adherence. METHODS: A subcohort analysis from a cluster-randomised controlled trial of 31 female soccer teams (coaches n=29, players (ages 13-18) n=258). Preseason and postseason questionnaires were used to assess knowledge and beliefs. Teams recorded FIFA 11+ adherence during the season. RESULTS: At baseline, 62.8% (95% CI 48.4% to 77.3%) of coaches and 75.8% (95% CI 71.5% to 80.1%) of players considered 'inadequate warm-up' a risk factor for injury. There was no effect of delivery method (OR=1.1; 95% CI 0.8 to 1.5) or adherence (OR=1.0; 95% CI 0.9 to 1.1) on this belief. At baseline, 13.8% (95% CI 1.3% to 26.4%) of coaches believed a warm-up could prevent muscle injuries, but none believed it could prevent knee and ankle injuries. For players, 9.7% (95% CI 6.1% to 13.3%), 4.7% (95% CI 2.1% to 7.3%) and 4.7% (95% CI 2.1% to 7.3%) believed a warm-up would prevent muscle, knee and ankle injuries, respectively. Years of playing experience were negatively associated with high adherence for coaches (OR=0.93; 0.88 to 0.99) and players (OR=0.92; 0.85 to 0.98). CONCLUSIONS: There were gaps in injury knowledge and beliefs, which differed for coaches and players. Beliefs did not significantly affect adherence to the FIFA 11+, suggesting additional motivational factors should be considered.

Clinical features and follow-up in patients with 22q11.2 deletion syndrome.

OBJECTIVE: To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease. STUDY DESIGN: A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis. RESULTS: The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations (P = .015) and speech disorders (P = .002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis. CONCLUSIONS: Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management.

Immunotherapy with an HIV-DNA Vaccine in Children and Adults.

Therapeutic HIV immunization is intended to induce new HIV-specific cellular immune responses and to reduce viral load, possibly permitting extended periods without antiretroviral drugs. A multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS) has been used in clinical trials in both children and adults with the aim of improving and broadening the infected individuals' immune responses. Despite the different country locations, different regimens and the necessary variations in assays performed, this is, to our knowledge, the first attempt to compare children's and adults' responses to a particular HIV vaccine. Ten vertically HIV-infected children aged 4-16 years were immunized during antiretroviral therapy (ART). Another ten children were blindly recruited as controls. Both groups continued their antiretroviral treatment during and after vaccinations. Twelve chronically HIV-infected adults were vaccinated, followed by repeated structured therapy interruptions (STI) of their antiretroviral treatment. The adult group included four controls, receiving placebo vaccinations. The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group. In the HIV-infected children, an increased specific immune response to Gag and RT proteins was detected by antigen-specific lymphoproliferation. Moreover, the frequency of HIV-specific CD8+ T-cell lymphocytes releasing perforin was significantly higher in the vaccinees than the controls. In the HIV-infected adults, increased CD8+ T-cell responses to Gag, RT and viral protease peptides were detected. No augmentation of HIV-specific lymphoproliferative responses were detected in adults after vaccination. In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults. Vaccinated children mounted transient new HIV-specific immune responses, including both CD4+ T-cell lymphoproliferation and late CD8+ T-cell responses. In the adult cohort, primarily CD8+ T-cell responses related to MHC class I alleles were noted. However, no clinical benefits with respect to viral load reduction were ascribable to the vaccinations alone. No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected.

Ensuring implementation success: how should coach injury prevention education be improved if we want coaches to deliver safety programmes during training sessions?

Coaches play a major role in encouraging and ensuring that participants of their teams adopt appropriate safety practices. However, the extent to which the coaches undertake this role will depend upon their attitudes about injury prevention, their perceptions of what the other coaches usually do and their own beliefs about how much control they have in delivering such programmes. Fifty-one junior netball coaches were surveyed about incorporating the teaching of correct (safe) landing technique during their delivery of training sessions to junior players. Overall, >94% of coaches had strongly positive attitudes towards teaching correct landing technique and >80% had strongly positive perceptions of their own control over delivering such programmes. Coaches' ratings of social norms relating to what others think about teaching safe landing were more positive (>94%) than those relating to what others actually do (63-74%). In conclusion, the junior coaches were generally receptive towards delivering safe landing training programmes in the training sessions they led. Future coach education could include role modelling by prominent coaches so that more community-level coaches are aware that this is a behaviour that many coaches can, and do, engage in.

Therapeutic DNA vaccination of vertically HIV-infected children: report of the first pediatric randomised trial (PEDVAC).

SUBJECTS: Twenty vertically HIV-infected children, 6-16 years of age, with stable viral load control and CD4+ values above 400 cells/mm(3). INTERVENTION: Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. RESULTS: Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. CONCLUSIONS: The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. TRIAL REGISTRATION: clinicaltrialsregister.eu _2007-002359-18IT.

High adherence to a neuromuscular injury prevention programme (FIFA 11+) improves functional balance and reduces injury risk in Canadian youth female football players: a cluster randomised trial.

BACKGROUND: A protective effect on injury risk in youth sports through neuromuscular warm-up training routines has consistently been demonstrated. However, there is a paucity of information regarding the quantity and quality of coach-led injury prevention programmes and its impact on the physical performance of players. OBJECTIVE: The aim of this cluster-randomised controlled trial was to assess whether different delivery methods of an injury prevention programme (FIFA 11+) to coaches could improve player performance, and to examine the effect of player adherence on performance and injury risk. METHOD: During the 2011 football season (May-August), coaches of 31 tiers 1-3 level teams were introduced to the 11+ through either an unsupervised website or a coach-focused workshop with and without additional on-field supervisions. Playing exposure, adherence to the 11+, and injuries were recorded for female 13-year-old to 18-year-old players. Performance testing included the Star Excursion Balance Test (SEBT), single-leg balance, triple hop and jumping-over-a-bar tests. RESULTS: Complete preseason and postseason performance tests were available for 226 players (66.5%). Compared to the unsupervised group, single-leg balance (OR=2.8; 95% CI 1.1 to 4.6) and the anterior direction of the SEBT improved significantly in the onfield supervised group of players (OR=4.7; 95% CI 2.2 to 7.1), while 2-leg jumping performance decreased (OR=-5.1; 95% CI -9.9 to -0.2). However, significant improvements in 5 of 6 reach distances in the SEBT were found, favouring players who highly adhered to the 11+. Also, injury risk was lower for those players (injury rate ratio, IRR=0.28, 95% CI 0.10 to 0.79). CONCLUSIONS: Different delivery methods of the FIFA 11+ to coaches influenced players' physical performance minimally. However, high player adherence to the 11+ resulted in significant improvements in functional balance and reduced injury risk.

Evaluation of how different implementation strategies of an injury prevention programme (FIFA 11+) impact team adherence and injury risk in Canadian female youth football players: a cluster-randomised trial.

BACKGROUND: Injury prevention programme delivery on adherence and injury risk, specifically involving regular supervisions with coaches and players on programme execution on field, has not been examined. AIM: The objective of this cluster-randomised study was to evaluate different delivery methods of an effective injury prevention programme (FIFA 11+) on adherence and injury risk among female youth football teams. METHOD: During the 4-month 2011 football season, coaches and 13-year-old to 18-year-old players from 31 tier 1-3 level teams were introduced to the 11+ through either an unsupervised website ('control') or a coach-focused workshop with ('comprehensive') and without ('regular') additional supervisions by a physiotherapist. Team and player adherence to the 11+, playing exposure, history and injuries were recorded. RESULTS: Teams in the comprehensive and regular intervention groups demonstrated adherence to the 11+ programme of 85.6% and 81.3% completion of total possible sessions, compared to 73.5% for teams in the control group. These differences were not statistically significant, after adjustment for cluster by team, age, level and injury history. Compared to players with low adherence, players with high adherence to the 11+ had a 57% lower injury risk (IRR 0.43, 95% CI 0.19 to 1.00). However, adjusting for covariates, this between-group difference was not statistically significant (IRR=0.44, 95% CI 0.18 to 1.06). CONCLUSION: Following a coach workshop, coach-led delivery of the FIFA 11+ was equally successful with or without the additional field involvement of a physiotherapist. Proper education of coaches during an extensive preseason workshop was more effective in terms of team adherence than an unsupervised delivery of the 11+ programme to the team. TRIAL REGISTRATION: ISRCTN67835569.

Safety and immunogenicity of a monovalent MF59®-adjuvanted A/H1N1 vaccine in HIV-infected children and young adults.

BACKGROUND: This Phase IV study evaluated the safety and immunogenicity of a two-dose, MF59®-adjuvanted (Novartis Vaccines, Marburg, Germany), monovalent, A/H1N1 pandemic influenza vaccination schedule in Human Immunodeficiency Virus (HIV) positive children and young adults. METHODS: A total of 83 children infected with HIV-1, and 37 non-immunocompromised, age-matched controls were enrolled. All participants received two vaccine doses administered three weeks apart. Antibody responses were assessed by haemagglutination assay at baseline, three weeks after each vaccine dose, and six months after immunization. Vaccines were evaluated according to European influenza vaccine licensure criteria. RESULTS: The investigational vaccine was well tolerated. After the first vaccine dose, seroconversion rates were significantly lower in HIV-positive patients (60%) than controls (82%), with GMTs of 419 and 600, respectively. No significant differences in seroconversion rates were observed between the two study groups in response to the second vaccine dose. Persisting antibody titers were similar for both HIV-positive and non-infected controls, six months after immunization. CONCLUSION: One dose of MF59-adjuvanted vaccine was sufficient to provide adequate levels of seroprotection against A/H1N1 influenza disease in HIV-positive children. However, a two-dose vaccination schedule may be optimal for this population.

Encouraging junior community netball players to learn correct safe landing technique.

OBJECTIVE: Behavioural factors and beliefs are important determinants of the adoption of sports injury interventions. This study aimed to understand behavioural factors associated with junior community netball players' intentions to learn correct landing technique during coach-led training sessions, proposed as a means of reducing their risk of lower limb injury. DESIGN: Cross-sectional survey. METHODS: 287 female players from 58 junior netball teams in the 2007/2008-summer competition completed a 13-item questionnaire developed from the Theory of Planned Behaviour (TPB). This assessed players' attitudes (four items), subjective norms (four), perceived behavioural control (four) and intentions (one) around the safety behaviour of learning correct landing technique at netball training. All items were rated on a seven-point bipolar scale. Cluster-adjusted logistic regression was used to assess which TPB constructs were most associated with strong intentions. RESULTS: Players had positive intentions and attitudes towards learning safe landing technique and perceived positive social pressure from significant others. They also perceived themselves to have considerable control over engaging (or not) in this behaviour. Players' attitudes (p<0.001) and subjective norms (p<0.001), but not perceived behavioural control (p=0.49), were associated with strong intentions to learn correct landing technique at training. CONCLUSIONS: Injury prevention implementation strategies aimed at maximising junior players' participation in correct landing training programs should emphasise the benefits of learning correct landing technique (i.e. change attitudes) and involve significant others and role models whom junior players admire (i.e. capitalise on social norms) in the promotion of such programs.

The PEDVAC trial: preliminary data from the first therapeutic DNA vaccination in HIV-infected children.

The PEDVAC study is the first trial designed to analyze safety and immunogenicity of a therapeutic vaccination with a multiclade multigene HIV DNA vaccine (HIVIS) in infected children. Twenty HIV-1 vertically infected children (6-16 years of age), on stable antiretroviral treatment for at least 6 months with HIV-1 RNA<50 copies/ml and stable CD4 counts (> 400 cells/mm³ or 25%) over 12 months of follow-up, were recruited into the study. Enrolled patients have been randomized into two arms: a control group of 10 children who continued previous antiretroviral treatment (HAART) (arm A) and a group of 10 children immunized intramuscularly with the HIVIS DNA vaccine in addition to previous HAART (arm B). Immunizations took place at week 0, 4, 12 and the boosting dose is planned at week 36. The 10 children in the vaccine group have received the first 3 priming doses of the HIVIS vaccine. Safety data showed good tolerance to the vaccination schedule. Mild cutaneous self-limeted reactions consisted of local irritation, usually itching or erythema +/- swelling at the injection site, were reported. No severe systemic adverse events have been observed. No vaccinated children had a decrease of CD4 T-cell counts from baseline. None experienced virological failure. Analysis of cellular immune responses was scheduled at week 0, 4, 12, 16, 20, 40, 60, 72 and 96 by standard lymphoproliferation assay, intracellular cytokine staining and cell-ELISA, a miniaturized assay to measure antigen-induced IFNγ secretion. Evaluation of these results is in progress and will provide key information on the status and changes of antigen specific immunity during HIV DNA immunization.

Immune deficiency caused by impaired expression of nuclear factor-kappaB essential modifier (NEMO) because of a mutation in the 5' untranslated region of the NEMO gene.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a key transcription factor that regulates both innate and adaptive immunity as well as ectodermal development. Mutations in the coding region of the IkappaB kinase gamma/NF-kappaB essential modifier (NEMO) gene cause X-linked ectodermal dysplasia with immunodeficiency. OBJECTIVE: To determine the genetic cause of recurrent sinopulmonary infections and dysgammaglobulinemia in a patient with a normal NEMO coding sequence and his affected brother. METHODS: TNF-alpha and IFN-alpha production in response to Toll-like receptor (TLR) stimulation was analyzed by ELISA, NEMO mRNA levels were measured by quantitative PCR, and NEMO protein expression was measured by Western blotting. NF-kappaB activation was assessed by nuclear translocation of p65 and luciferase reporter gene assays. RESULTS: TLR-induced TNF-alpha and IFN-alpha production by PBMCs was impaired in the patient and his brother. Sequencing of the patient's NEMO gene revealed a novel mutation in the 5' untranslated region, which was also present in the brother, resulting in abnormally spliced transcripts and a 4-fold reduction in mRNA levels. NEMO protein levels in EBV transformed B cells and fibroblasts from the index patient were 8-fold lower than normal controls. NF-kappaB p65 nuclear translocation in the patient's EBV B cells after TLR7 ligation was defective. NF-kappaB-dependent luciferase gene expression in IL-1-stimulated fibroblasts from the patient was impaired. CONCLUSION: This is the first description of immune deficiency resulting from low expression of a normal NEMO protein.

Role of reduced intensity conditioning in T-cell and B-cell immune reconstitution after HLA-identical bone marrow transplantation in ADA-SCID.

The treatment of choice for severe combined immunodeficiency is bone marrow transplantation from an HLA-identical donor sibling without conditioning. However, this may result in low donor stem cell chimerism, leading to reduced long-term immune reconstitution. We compared engraftment, metabolic, and T-cell and B-cell immune reconstitution of HLA-identical sibling bone marrow transplantation performed in 2 severe combined immunodeficiency infants with adenosine deaminase deficiency from the same family treated with or without a reduced intensity conditioning regimen (busulfan/fludarabine). Only the patient who received conditioning showed a stable mixed chimerism in all lineages, including bone marrow myeloid and B cells. The use of conditioning resulted in higher thymus-derived naïve T cells and T-cell receptor excision circles, normalization of the T-cell repertoire, and faster and complete B-cell and metabolic reconstitution. These results suggest the utility of exploring the use of reduced intensity conditioning in bone marrow transplantation from HLA-identical donor in severe combined immunodeficiency to improve long-term immune reconstitution.

Delayed early antiretroviral treatment is associated with an HIV-specific long-term cellular response in HIV-1 vertically infected infants.

Antiviral T-cell immune responses appear to be crucial to control HIV replication. Infants treated before the third month of life with highly active antiretroviral treatment (HAART) did not develop a persistent HIV-specific immune response. We evaluated how delayed initiation of HAART after 3 months of age influences the development of HIV-1-specific T-cell responses during long-term follow-up in 9 HIV-1 vertically infected infants. These data suggest that a longer antigenic stimulation, due to a larger window for therapeutic intervention with HAART, is associated with the establishment of a persistent specific HIV immune response resulting in a long-term viral control of vertically infected infants.

Successful simplification of protease inhibitor-based HAART with triple nucleoside regimens in children vertically infected with HIV.

OBJECTIVE: To assess the virological, immunological and metabolic effects of switching from an efficacious first-line protease inhibitor (PI)-based HAART to a simplified triple nucleoside reverse transcriptase inhibitor (NRTI) regimen in children vertically infected with HIV. DESIGN: Prospective, open-label, before-after study of 20 vertically infected children with at least 12 consecutive months of undetectable viral load under a PI-based HAART and no previous history of NRTI treatment. METHODS: At study entry, HAART was shifted to a triple-NRTI combination. RESULTS: The children were aged 2 to 18 years (median, 7.9) and were followed for 96 weeks. All were receiving a PI-based regimen for an average duration of 4 years before enrollment. At study entry, 12 patients (60%) switched to abacavir, 5 (25%) to lamivudine; 2 (10%) to zidovudine and 2 to didanosine (10%). All but one patient maintained plasma HIV RNA < 50 copies/ml during the entire follow-up. No immunological failure was observed at week 96. A trend of normalization (P < 0.001) of T cell receptor Vbeta families of the CD8 cell subset was detected in 19/20 (95%), with an increased HIV-specific CD8 T cell response (P < 0.01) in 17/20 (85%). Dyslipidaemia significantly improved during the follow up (P < 0.001). No new cases of lipodystrophy were detected. CONCLUSIONS: Switching to triple-NRTI regimens in selected HIV-infected children with an extremely low likelihood of harbouring nucleoside-associated mutations maintains viral suppression and immunological function, improving metabolic abnormalities and the effort to take medication for up to 96 weeks.

Switching from protease inhibitor-based-HAART to a protease inhibitor-sparing regimen is associated with improved specific HIV-immune responses in HIV-infected children.

To evaluate the effects of switching from successful long-term protease inhibitor (PI)-based HAART to a three nucleoside reverse transcriptase inhibitor PI-sparing regimen, viral load quantification, HIV-specific lymphoproliferative assay and T-cell receptor (TCR) spectratyping were performed during 96 weeks of simplification follow-up in 19 HIV-infected children. Our data showed that simplification of therapeutic strategies acts positively on immune competence in HIV paediatric patients. Our children maintained viral suppression, increased lymphoproliferative responses and normalized TCRBV repertoire on the CD8 subset.