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Objectives: Although widely recommended, data on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) efficacy in HIV‐1‐infected children/adolescents are mainly extrapolated from studies in adults and one paediatric trial in which subjects have good treatment adherence. This study aimed to provide data about the risk of virological failure (VF) and acquired genotypic resistance in children and adolescents receiving BIC/FTC/TAF in a real‐world setting. Methods: This retrospective monocentric study included 74 paediatric patients who received BIC/FTC/TAF during ≥6 months in 2019–2023. VF was defined as not achieving a plasma viral load <50 copies/mL within 6 months of BIC/FTC/TAF initiation or as experiencing virological rebound ≥50 copies/mL. Results: Most patients were antiretroviral therapy (ART)‐experienced (93.2%), previously exposed to integrase inhibitors (85.1%) and displayed viral suppression at baseline (67.6%). Their median age was 11.2 years [interquartile range (IQR): 8.8–15.2]. BIC/FTC/TAF introduction reduced treatment burden in most ART‐experienced subjects. Genotypic susceptibility score of BIC/FTC/TAF was ≥2 in all cases. Median follow‐up was 40 months (IQR: 21–46). VF occurred in 28 people (37.8%), more frequently in the case of VF versus viral suppression at baseline (68% vs. 26%, P = 0.02). BIC/FTC/TAF was interrupted for suspected intolerance in only one case (1.4%). Nucleoside reverse transcriptase inhibitor (NRTI) mutation (T69D/N) emerged in one patient (3.6% of VF) after 47 months of continuous detectable viraemia while on ART. No acquisition of mutations in the integrase gene was observed. Conclusion: Because of its high genetic barrier to resistance, BIC/FTC/TAF could be especially useful in the paediatric population, in which the risk of poor treatment adherence and VF is high. [ABSTRACT FROM AUTHOR]

Research has been conducted on treatment of HIV-infected children. The relationship between plasma concentrations of antiretroviral drugs administered during daily medical consultations has been investigated via the use of the random sample timing approach, and the details are reported.

Objectives: Increased weight gain with dolutegravir use is increasingly scrutinized in adults, but published data in paediatrics are limited and conflicting. This study aimed to provide long-term data about changes in body mass index (BMI) in French children (aged 3-9 years) and adolescents (aged 10-17 years) receiving dolutegravir., Patients and Methods: This retrospective monocentric study included 97 subjects who received a dolutegravir-based regimen for ≥12 months in 2014-2021. We evaluated the mean change in age- and sex-matched standardized BMI z score (BMIz) per year of dolutegravir exposure and compared the dynamics of BMIz change during the 12 months pre- vs. post-dolutegravir use when these data were available., Results: At the time of dolutegravir initiation, most of the subjects were antiretroviral therapy (ART) experienced (89.7%), displayed virological suppression (73.2%), and had normal weight for their age (78.4%). Median follow-up was 30 months (interquartile range [IQR] 19-45). The mean rate of change in BMIz was +0.03 z score/year of dolutegravir exposure (95% confidence interval [CI] -0.08-0.13) in the entire cohort. It was lower in children than in adolescents (-0.08 [95% CI -0.23-0.08] vs. +0.16 [95% CI 0.06-0.26], respectively; p = 0.04) and in individuals with baseline BMI ≥50 th percentile than in those with lower BMI (-0.06 [95% CI -0.14-0.01] vs. +0.08 [95% CI -0.07-0.23], respectively; p = 0.001). Trajectories of BMIz change 12 months pre- vs. post-dolutegravir were similar, except in subjects with baseline BMI ≥50 th percentile, whose rate of BMIz change was lower post-dolutegravir (difference: -0.23 [95% CI -0.46-0.00]; p = 0.04)., Conclusion: We found no evidence of change in BMIz in French children initiating dolutegravir. These reassuring findings maintain the primary position of dolutegravir among paediatric therapeutic options., (© 2022 British HIV Association.)

Objectives: Although widely recommended, data about dolutegravir efficacy in HIV-1-infected children/adolescents are scarce, limited to short-term follow-up and mainly extrapolated from studies in adults with good adherence to treatment. This study aimed to provide long-term data about the risk of virological failure (VF) and acquired genotypic resistance in children and adolescents receiving dolutegravir., Methods: This retrospective monocentric study included 134 paediatric patients who received a dolutegravir-based regimen for ≥ 12 months in 2014-2020. Virological failure was defined as not achieving a plasma viral load (pVL) < 50 copies/mL within 3 months of dolutegravir initiation or as experiencing virological rebound ≥ 50 copies/mL., Results: Most of the subjects were antiretroviral therapy-experienced (90.3%), naïve from integrase inhibitors (90.3%) and displayed virological suppression at baseline (63.4%). Their median (interquartile range, IQR) age was 12.0 (8.0-15.8) years. Genotypic susceptibility score of the new regimen was ≥ 2 in 96% of cases. Median (IQR) follow-up was 34 (22-50) months. Virological failure occurred in 43 people (32.1%), more frequently where the baseline pVL was ≥ 50 copies/mL (67.4% vs. 22.0%, P < 0.01). M184V/I mutations in the reverse transcriptase gene were newly detected in three people with VF. Resistance to dolutegravir (mutations G118R and E138A in the integrase gene) emerged in one adolescent (0.7% of subjects, 2.3% of those with VF)., Conclusions: Whereas VF is relatively common on dolutegravir in the paediatric population, regimens associating dolutegravir with more than one fully active drug were associated with a low rate of emergent drug resistance. This result strengthens the recommendation of dolutegravir as part of preferred combinations in children/adolescents., (© 2021 British HIV Association.)

Background: The early initiation of antiretroviral therapy (ART) in HIV-1-infected infants reduces mortality and prevents early CD4 T-cell loss. However, the impact of early ART on the immune system has not been thoroughly investigated in children over five years of age or adolescents. Here, we describe the levels of naive CD4 and CD8 T lymphocytes (CD4/CD8T N ), reflecting the quality of immune reconstitution, as a function of the timing of ART initiation (early (<6 months) versus late (≥24 months of age))., Methods: The ANRS-EP59-CLEAC study enrolled 27 children (5-12 years of age) and nine adolescents (13-17 years of age) in the early-treatment group, and 19 children (L-Ch) and 21 adolescents (L-Ado) in the late-treatment group. T lymphocytes were analyzed by flow cytometry and plasma markers were analyzed by ELISA. Linear regression analysis was performed with univariate and multivariate models., Results: At the time of evaluation, all patients were on ART and had a good immunovirological status: 83% had HIV RNA loads below 50 copies/mL and the median CD4 T-cell count was 856 cells/µL (interquartile range: 685-1236 cells/µL). In children, early ART was associated with higher CD8T N percentages (medians: 48.7% vs. 31.0%, P = 0.001), and a marginally higher CD4T N (61.2% vs. 53.1%, P = 0.33). In adolescents, early ART was associated with low CD4T N percentages and less differentiated memory CD8 T cells. CD4T N and CD8T N levels were inversely related to cellular activation and gut permeability., Conclusion: In children and adolescents, the benefits of early ART for CD8T N were clear after long-term ART. The impact of early ART on CD4T N appears to be modest, because pediatric patients treated late respond to HIV-driven CD4 T-lymphocyte loss by the de novo production of T N cells in the thymus. Our data also suggest that current immune activation and/or gut permeability has a negative impact on T N levels., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02674867., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Frange, Montange, Le Chenadec, Batalie, Fert, Dollfus, Faye, Blanche, Chacé, Fourcade, Hau, Levine, Mahlaoui, Marcou, Tabone, Veber, Hoctin, Wack, Avettand-Fenoël, Warszawski and Buseyne.)

Objective(s): To describe the clinical, virological and immune characteristics of internationally adopted children on arrival in France and after 6-months follow-up., Design: Multicenter retrospective study., Methods: 30 centers from 24 cities were asked to include, after informed consent, HIV+ children living in France and internationally adopted between 1st Jan 2005 and 1st Jan 2015. Sociodemographic, medical and biological variables collected during the first medical evaluation in France and 6 months later were analyzed., Results: 41 HIV+ adoptees were included (female: 56%; median age: 3.91 years) in 14 centers. Adoptees tend to represent an increasing part of newly diagnosed HIV positive children over the years. The majority came from East-Asia. At arrival, one child was diagnosed with lymphobronchial tuberculosis and three with latent chronic hepatitis B, cleared HBV infection and chronic active hepatitis C, respectively. The mean CD4% was 32.8 ± 9% (range: 13-49%). The 34 children (83%) have been initiated on treatment from their countries of origin. Of these, 25 (74%) had an undetectable viral load (VL) on arrival. Resistance to ART was detected in five. At 6 months, 36 adoptees received ART, and the VL was undetectable in 29 children (71%), with one acquired resistance to NRTI & NNRTI., Conclusions: An increasing number of HIV-infected children have been internationally adopted in France since 2005. Most of the children have been initiated on treatment from their countries of origin, had good immunity, with few opportunistic infections, and infrequently detectable VL. Low level of mutation conferring resistance was detected., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To describe the prevalence of transmitted drug resistance (TDR) among 84 children newly diagnosed with HIV in France in 2006-17., Methods: HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 Stanford list of mutations and the 2017 French National Agency for AIDS Research (ANRS) algorithm. A genotypic susceptibility score (GSS) was estimated for each first-line recommended ART combination., Results: Patients were mainly infected through mother-to-child transmission (MTCT) (73/84; 86.9%), but only 18 children (24.7% of vertically infected patients) were previously exposed to antiretroviral prophylaxis from MTCT. Non-B variants were identified in 90.5% (76/84) of patients. The frequency of TDR was 8.3% (7/84) using the 2009 Stanford list and 16.7% (14/84) using both the Stanford list and the 2017 ANRS algorithm. The prevalence of PI-, NRTI-, efavirenz/nevirapine-, etravirine/rilpivirine- and doravirine-associated RAMs was 0%, 3.6%, 6.0%, 11.9% and 2.4%, respectively. Single-, dual- and triple-class resistance was present in 15.5%, 1.2% and 0% of cases, respectively. Additionally, 3/60 (5%) strains had integrase inhibitor (INI)-related RAMs (an isolated E157Q mutation, which could mostly affect the susceptibility to raltegravir/elvitegravir rather than that to dolutegravir). Among the 18 children exposed to MTCT prophylaxis, RAMs were identified in only 1 case (5.6%). The proportion of fully active combinations (GSS = 3) was ≥97.6%, ≥94.1%, ≥92.9% and ≥89.3% for PI-, INI-, efavirenz/nevirapine- and rilpivirine-based regimens, respectively., Conclusions: The proportion of NRTI- and NNRTI-related TDR in children is lower in France than in low- and middle-income countries. However, we suggest favouring PI- or dolutegravir- over NNRTI-based combinations to treat newly diagnosed HIV-infected children, even in the absence of previous exposure to antiretroviral prophylaxis of MTCT.

Objectives: To assess the safety and efficacy of a dolutegravir-based regimen in perinatally HIV-1-infected adolescents., Patients and Methods: We conducted a retrospective multicentre study of 50 adolescents beginning dolutegravir-based treatment regimens between January 2014 and December 2015. Clinical and biological data collected before and after dolutegravir initiation were analysed. The primary endpoint was the proportion of patients achieving a plasma viral load (PVL) <50 copies/mL within 3 months of dolutegravir initiation (for patients with detectable viraemia at baseline) and maintaining virological suppression (PVL <50 copies/mL) until the last follow-up visit (for all patients)., Results: Virological suppression was noted for 17/50 adolescents at baseline. Dolutegravir-based regimens maintained virological success in 14/17 patients (82%). The other three patients experienced a transient viral rebound, before PVL fell to < 50 copies/mL again, with no need to change the antiretroviral regimen. Thirty-three viraemic adolescents were enrolled. All but one had already received antiretroviral drugs. Virological success was achieved and maintained in 19/33 subjects (58%). Another three adolescents with initial virological failure had an undetectable PVL at the end of follow-up, with reinforced measures to improve compliance. Overall, sustained virological success was observed in 66% of patients and 78% of patients had an undetectable PVL at the last visit. Dolutegravir was well tolerated. Only one patient stopped treatment for severe drug-related adverse effects (dizziness and sleep disturbance). No emergence of resistance mutations was observed in patients with virological failure., Conclusions: Dolutegravir was safe and virologically effective in these patients, for whom multiple interventions were required to improve compliance., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Resilience of perinatally HIV-infected youth in European countries is poorly studied. Life satisfaction and expectations for adulthood are rarely examined., Objective: This cross-sectional, descriptive study of a French cohort of 54 perinatally HIV-infected adolescents raised in France (age 14-20 years) aimed to (1) evaluate their psychosocial adjustment, (2) identify their expectations for adulthood and (3) delineate risk and protective factors associated with mental health, life satisfaction, and HIV-1 viral load level., Method: Medical evaluation, psychological semi-structured interview, and self-report questionnaires were used., Results: All the adolescents had been receiving Highly Active Anti-Retroviral Therapy (HAART) for 9 to 11 years and 2/3 were healthy with controlled viral load (<50 copies/mL). The majority had medium to high levels of life satisfaction. They viewed HIV as having only minor impact on their current daily life and had positive expectations for adulthood. However, 46% exhibited psychiatric symptomatology. Multivariable analysis showed that having a deceased parent and current worries about HIV were substantial risk factors for psychiatric symptoms. Having two living parents and being satisfied with life were protective factors for mental health. Good quality of caregiver-adolescent relationships and high life satisfaction were significant protective factors for controlled viral load., Conclusion: These data indicate psychosocial resilience among perinatally HIV-1 infected adolescents with 10 years of HAART treatment. These findings demonstrate the influence of life satisfaction, parent's life status and quality of caregiver-adolescent relationships on resilience and health outcomes in these patients. We conclude that healthcare providers should attend to these factors.

We describe 48 cases of HIV-1-infected children newly diagnosed in 2006 to 2012 in France. Native French children were born to women whose HIV testing were mostly missed (13.6%), offered late (9.1%) or negative at start of pregnancy and not subsequently reoffered (54.5%). HIV testing of immigrant children were performed late after arrival, despite prompt access to healthcare structures. HIV testing strategies need to be improved.

Background: Vitamin D insufficiency and HIV infection are both risk factors for chronic disorders, so it is important to consider vitamin D status in HIV-infected patients., Methods: We prospectively investigated serum 25-hydroxyvitamin D (25(OH)D) concentrations, determined by radioimmunoassay, in 113 HIV-infected children (age≤24 years) and 54 healthy controls matched for age and phototype. We assessed the prevalence of vitamin D deficiency and insufficiency (VDD and VDI) defined as 25(OH)D titers of <10 ng/mL and between 10 and 30 ng/mL, respectively, and their predictive factors., Results: The overall prevalence of VDD and VDI was 38.9% and 58.7%, respectively. Mean serum 25(OH)D concentrations were significantly higher in the HIV group than the control group (14.2±6.9 ng/mL vs. 10.4±5 ng/mL, P<0.001). Variables significantly associated with low serum 25(OH)D concentrations in HIV-infected children were dark phototype (P<0.001) and age (r=-0.19, P=0.03). Patients receiving efavirenz had a trend toward lower serum 25(OH)D concentrations (11.1±4.6 ng/mL vs. 14.6±7 ng/mL, P=0.1). Dark phototype was the only independent risk factor for VDD in HIV-infected children (odds ratio=14.6; 95% confidence interval: 2.4-89.9, P=0.004)., Conclusions: VDD and VDI were common in both HIV-infected and control groups, and serum 25(OH)D concentrations were significantly lower in controls than in HIV-infected children.

Objective: The risk of virologic failure and selection of resistant strains remains a challenge in HIV-1 perinatally infected children. HIV-1 coreceptor usage was determined in HAART-failing children followed in Necker Hospital (Paris, France) in order to estimate the proportion of these patients who may benefit from CCR5-antagonists therapy., Methods: HIV-1 coreceptor usage was determined with the SVM(Geno2pheno10%) algorithm in 51 children with virologic failure after a median treatment exposure of 7.8 years., Results: CXCR4-tropic strains were found in 31.4% of the patients. CXCR4 usage was associated with high HIV-1 DNA (P=0.01), old age (P=0.02), long ART cumulative exposure (P=0.006), and previous exposure to high number of different drugs (P=0.03) and ART combinations (P=0.03) in univariate analysis. Selection of resistant viruses and current exposure to a darunavir-based HAART tended to be more frequent in the CXCR4 group compared with the children infected with CCR5-tropic strains (P=0.06). In multivariate analysis, CXCR4 usage was exclusively correlated with HIV-1 DNA (P=0.03), which accurately reflects the cumulative exposure to viral replication over the whole duration of HIV infection., Conclusion: Two-thirds of HAART-failing children could benefit from CCR5 antagonists-based strategies, even in case of triple-class virologic failure. Such therapy should be discussed more appropriately at early stages of infection, when CCR5-tropic strains are most frequently isolated. However, before considering such strategies, further studies are needed to evaluate the efficacy and the tolerability of CCR5 antagonists in this pediatric population., (© 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins)

Background: Lopinavir/ritonavir (LPV/r) is now the protease inhibitor regimen of choice in the first-line antiretroviral therapy for children <6 years of age., Methods: We included all the human immunodeficiency virus (HIV) type 1-infected highly active antiretroviral therapy (HAART)-naive children who started an LPV/r-based regimen between 2000 and 2009 at the Necker Hospital (Paris, France). Virologic failure (VF) was defined as an HIV-RNA ≥50 copies/mL. Resistance genotypic test was performed in case of VF., Results: A total of 43 children were included at a median age of 4.8 years (1.8-8.0). Median level of HIV RNA and percentage of CD4 cell count was 5.5 log₁₀ copies/mL (4.6-6) and 15% (8-27.5), respectively. HAART included LPV/r and 2 nucleoside reverse-transcriptase inhibitors, mainly lamivudine (3TC), zidovudine, and/or abacavir. The median follow-up period was 36 months (18-72). Less than 50 copies/mL of HIV RNA was observed in 46%, 67%, and 70% of the children at months 6, 9, and 12, respectively. In all, 20 children (46.5%) experienced a VF. The risk factors of primary VF were a young age and a low socioeconomic status. The genotypic resistance test, performed for 18 of 20 children with VF, revealed 1 LPV/r-resistant virus and protease inhibitor-related major mutations without LPV/r resistance in 2 other children. Of the 18 children with VF, 15 received a 3TC-based HAART: 12 of 15 (80%) harbored a 3TC-resistant virus. No virus resistant to zidovudine or abacavir was found., Conclusion: In all, 70% of HAART-naive children had virologic success at month 12. The selection of LPV-resistant strains was a rare event. A high rate of selection of 3TC-mutations strengthens the recommendation to prefer a first-line 3TC-sparing regimen, particularly for children with risk factors of poor adherence.

A single-center cross sectional evaluation of beta-2 micro-globinuria as a marker of proximal renal tubule damage in 92 HIV-infected children showed that tenofovir treatment was significantly associated with very high abnormal values. In view of the very long duration of treatments for HIV infection, their possible consequences for the child's growing body should be carefully evaluated.

In the USA and West Europe, nearly 80% of HIV-1-infected adults, experiencing virologic failure, harbored virus strain resistant to at least one antiretroviral drug. Limited data are available on antiretroviral drug resistance in pediatric HIV infection. The aims of this study were to analyze prevalence of HIV-1 drug resistance and to identify risk factors associated with resistance in this population. Prevalence of genotypic resistance was estimated retrospectively in treated children who experienced virologic failure (with HIV-1-RNA > 500 copies/ml) followed in Necker hospital between 2001 and 2003. Among 119 children with resistance testing, prevalence of resistance to any drug was 82.4%. Resistance ranged from 76.5% to nucleoside reverse transcriptase inhibitor (NRTI), to 48.7% to non-nucleoside reverse transcriptase inhibitor (NNRTI) and 42.9% to protease inhibitor (PI). Resistance to at least one drug of two classes and three classes (triple resistance) was 31.9 and 26.9%, respectively. Resistance was not associated with geographic origin, HIV-1 subtype, and CDC status. In multivariate analysis, resistance to any drug remained associated independently with current low viral load and high lifetime number of past PI. Triple resistance was independently associated with the high lifetime number of past PI and with gender, particularly among children aged 11 years old or more with a prevalence seven times higher in boys than in girls. In conclusion, antiretroviral resistance is common among treated HIV-1-infected children and prevalence was similar with those observed in adult population in the same year period. However, adolescent boys seem to be at greater risk.

Pediatric HIV-1 infections are still being diagnosed in France, despite the efficacy of prophylactic treatment to prevent mother-to-child transmission. To describe the characteristics and mode of infection of these children, we retrospectively analysed data of 59 children diagnosed with the HIV-1 infection between January 2000 and June 2005 in a Parisian university hospital. Twenty of these children had been born in France, and none had received appropriate prophylaxis (insufficient, not taken or given too late). Six received no preventive treatment due to failures in screening: three mothers were HIV-seronegative at the start of pregnancy and no test was carried out for the other three. At diagnosis, four had a severe immune deficiency (CD4 cells <15%). The 39 children born abroad were diagnosed at a median age of 3 years (range: 3 months-16 years), sometimes several years after their arrival in France. The clinical, virological and immunological status of these children was poorer than that of the children born in France: 18 had less than 15% CD4 cells. In contrast, the response to treatment of the children born in France was not as good as that of the children born abroad. The HIV-1 screening and prevention programme for pregnant women could be improved. Some children infected following the failure of prevention are at high risk of subsequent treatment failure. HIV-1 infection should be taken into consideration in children born in countries with a high prevalence of HIV, even if they have been living in France for several years and present no symptoms.

Background: Pediatric experience with atazanavir combined with antiretroviral drugs administered once daily is very limited., Objective: The objective of this prospective, single-center observation study was to evaluate efficacy and tolerance of once-a-day ritonavir-boosted atazanavir, including treatment., Results: Antiretroviral treatment of 23 children and adolescents with a median age of 16 years (range, 10-19 years) was changed to a single daily dose of a combination of ritonavir-boosted atazanavir and 2 other nucleoside or nonnucleoside analogs. The single daily dosing was expected to improve adherence to treatment. The mean follow-up period was 12 months (range, 6-17 months). At the time of the treatment switch, the previous treatment had been effective in 11 children (plasma viral load [pVL] <50 copies/mL) and not effective in 12 (pVL >50 copies/mL). None of the viral genotypes had resistance to atazanavir. The susceptibility score for the drugs used in combination with atazanavir (GSS) was at least 1.5 in 12 of 20 children. The atazanavir dose was 300 mg per day for children weighing more than 50 kg and 200 mg per day for children weighing 30 to 50 kg, in all cases associated with 100 mg ritonavir. During follow up, the mean atazanavir plasma concentration at 12 to 15 hours was 2.18 +/- 1.19 mg/L. Tolerance was good in most patients, but 4 children chose to stop treatment because of icterus (n = 2) or persistent nausea and vomiting (n = 2). In 6 of the 12 children in whom treatment was not virologically effective before the switch, pVL was below 50 copies/mL after 1 to 3 months of treatment. Poor compliance and virologic failure persisted in the other 6 children. Seven of the 11 children with good virologic control before the switch continued to have undetectable pVL but 4 experienced virologic failure after 1, 1, 3 or 12 months of treatment despite good compliance. Insufficient antiviral potency of associated drugs could have been the cause of 2 of these 4 unexpected virologic failures., Conclusion: In these children with extensive previous treatment, the change to a once-daily treatment, including ritonavir-boosted atazanavir, was associated with a significant risk of virologic failure.

Objective: To assess the effects of a peer support group therapy on HIV-infected adolescents., Design: A prospective study of a cohort of HIV-infected adolescents participating or not participating in a psychodynamic oriented, emotional support group., Methods: From a group of 30 perinatally HIV-infected adolescents who attended an outpatient clinic, 10 agreed to participate in the peer support group (group 1), 10 declined (group 2) and 10 others who lived too far from the clinic were not invited to participate (group 3). The three groups were compared at baseline and 2 years later using the outcome measures: perceived illness experience scale, perceived treatment inventory, self-esteem inventory., Results: At baseline, the three groups had similar characteristics overall. The adolescents' self-esteem was in the normal range. After 2 years, worries about illness had decreased in group 1, whereas the scores had increased or remained the same for the other adolescents (P = 0.026). The adolescents in group 1 had less negative perception of treatment at 2 years than those in groups 2 and 3 (P = 0.030). After intervention, the percentage of adolescents with an undetectable viral load had increased in group 1 from 30 to 80% (P = 0.063) but was unchanged in groups 2 and 3. Considering the three groups altogether, the decrease in the viral load correlated with improvement of the perceived treatment inventory (Spearman R = 0.482 P = 0.015)., Conclusions: : This pilot study suggests that a peer support group intervention is associated with an improvement in adolescents' emotional well being, and that this can have a positive influence on medical outcomes.

Predictive factors of the virologic success of the use of lopinavir/ritonavir (LPV/r) in HIV-infected children are unknown, especially in children who have been pretreated with protease inhibitors (PIs). This longitudinal, single-center, observational study included 69 children (21 PI-naive and 48 PI-experienced) who had received LPV/r for at least 3 months. The mean (+/- SD) age was 10.3 +/- 4.8 years, and the mean baseline of CD4 percentage and HIV-1 RNA was 14.9% +/- 9.8% and 4.8 +/- 1.05 log10 copies/mL, respectively. The mean duration of follow-up was 16.5 +/- 8.3 months. At 6, 12, and 18 months, 52%, 57%, and 49% of all children, respectively, had a viral load less than 50 copies/mL. The risk of virologic failure, defined as 2 consecutive viral loads greater than 1000 copies/mL, was significantly higher when the children were previously treated with PIs and when the baseline LPV mutation score exceeded 3 mutations. In the pretreated children, the ratio of the plasma LPV maximal concentration to the baseline LPV score mutation was also associated with failure, independently of resistance score. Finally, in children failing an LPV-containing regimen, accumulation of additional PI-associated resistance mutations was evidenced in viral isolates from children with prior PI treatment, even with viral replication levels less than 10,000 copies/mL. In pretreated children, LPV plasma levels should be optimized in an attempt to achieve sufficient drug concentrations to overcome the resistance level.

A case of a low grade chondrosarcoma of the cricoid cartilage which had been diagnosed initially as a chondroma is presented. The tumour recurred twice after limited surgical resections. Total laryngectomy was inevitable due to near total involvement of the cricoid cartilage and subsequent histological examination revealed a low grade chondrosarcoma. We have discussed in brief, the diagnosis and treatment of chondrosarcomas of the larynx and support the view of conservative surgical management for low grade tumours as they are slow growing and metastases are infrequent. A total laryngectomy may be reserved for salvage or primarily when more than half of the cricoid cartilage needs to be resected. Histological grading reveals the biological behaviour of the tumour and CT scans help in planning the surgery. A regular follow-up is necessary for early detection of recurrences and metastases.

We conducted a prospective, open study of oral itraconazole therapy (5 and then 10 mg/kg per day) to assess tolerance and potential efficacy in preventing fungal infections in patients with chronic granulomatous disease. Thirty-two patients were enrolled in one center between 1985 and 1991. Tolerance was excellent in all cases. Poor compliance was suspected in three cases. Two patients were excluded from efficacy analysis because itraconazole was used as part of therapy for pulmonary aspergillosis. Of 30 patients, 3 developed a fungal (Aspergillus) lung infection, an incidence 3.4/100 patient-years versus 11.5 in a historical control group that did not receive any prophylaxis (p = 0.13) and 9.55 in a historical group of patients who received daily ketoconazole prophylaxis (p = 0.19). The percentage of patients infected with Aspergillus was significantly different: 10% in the itraconazole group versus 34.4% in the untreated group (p = 0.013). These results require further evaluation through a comparative randomized trial to assess the possible benefit of itraconazole prophylaxis in patients with chronic granulomatous disease.

The evaluation of a neutropenia first must document its etiology. Besides the particular etiological aspects in the newborn, neutropenia in a child may be 1) acquired, 2) constitutional, part of a complex genetic disease, 3) constitutional, isolated. Primary acquired neutropenia, also called benign chronic neutropenia, is the most frequent cause of chronic neutropenia in children; it is usually well tolerated and has a frequent favorable outcome in 12-14 months. Many complex genetic diseases include a neutropenia, among which several immunologic disorders that must be ruled out before considering the diagnosis of isolated constitutional neutropenia. Infantile agranulocytosis is the main primary constitutional neutropenia. It may be sporadic or hereditary (autosomal recessive or dominant inheritance) and is present at birth. It is profound, usually < 0.5 G/l (< 500/mm3) and exposes to severe pyogenic and fungal infections. In the neonatal period neutropenia must primarily suggest a bacterial infection, although other etiologies have to be known, particularly neonatal neutropenia caused by passive transfer of maternal antibodies and neutropenia related to gravidic maternal hypertension. The treatment of severe chronic neutropenia is directed towards the prevention of infections. It includes prophylactic antibiotherapy, the most commonly used one being the trimetroprim-sulfamethoxazole association, and granulocyte colony stimulating factor (G-CSF). G-CSF has considerably improved the condition of patients; it is usually well tolerated, but secondary effects have been reported (hypersplenism, glomerulonephritis, osteoporosis, vasculitis), and a potential leukemogenic risk has been evoked.

The use of Mycobacterium bovis/Bacillus Calmette-Guérin (BCG) to vaccinate against tuberculosis remains controversial. The development of tuberculosis in human immunodeficiency virus (HIV)-infected children demands specific evaluation of the risk/benefit ratio of BCG vaccination in this situation. In our institution 9 of 68 HIV-infected children vaccinated with BCG before the diagnosis of HIV infection was suspected developed vaccine-related complications: 7 of these children had a large satellite adenopathy with or without skin fistulae, whereas the other 2 had disseminated BCG infection beyond the satellite ganglion (involvement of the spleen and mesenteric and mediastinal lymph nodes in one case and the liver and lungs in the other). The children were vaccinated soon after birth; no particular problems were observed at that time, but complications appeared 3 to 35 months later. All but one of these children had a rapidly progressive form of HIV disease. The possibility of delayed local or disseminated BCG infection must be considered in analysis of the risk/benefit ratio of vaccination of HIV-infected children. The prognosis of HIV infection must be taken into account, even if the child is asymptomatic when vaccination is being considered.

The clinical, biochemical, morphological, and evolutive features of autoimmune hepatitis associated with serum smooth muscle antibodies of anti-actin specificity were retrospectively analyzed in 31 children and adolescents. Cirrhosis was present at diagnosis in all but six patients, including nine of the 12 diagnosed within 6 months from the onset. In 15 children, one or more associated diseases of an immune-mediated mechanism were present, including chronic arthritis, sclerosing cholangitis, inflammatory bowel disease, and cutaneous vasculitis. All patients were treated with prednisone and azathioprine with normalization or improvement of liver function tests: 28 children are currently alive after a mean follow-up of 4 years, 10 months. Treatment was interrupted in four patients only. Two patients died of liver failure in spite of immunosuppressive therapy before the era of liver transplantation. In spite of prolonged therapy, five other patients ultimately required liver transplantation during adolescence or early adulthood. These results (a) further define a group of autoimmune hepatitis in children characterized by the presence of serum anti-actin antibodies; (b) indicate that immunosuppressive therapy improves liver function, although in most cases it must be continued for a long period to maintain remission; and (c) suggest that progressive liver failure may occur in early adulthood and may require liver transplantation.