Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Signes cliniques de mauvaise tolérance évocateurs d'infection bactérienne sévère chez l'enfant fébrile de plus de deux ans

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Indices cliniques d'infection bactérienne sévère chez l'enfant fébrile de moins de vingt-quatre mois

Identifier les signes cliniques de mauvaise tolérance de la fièvre, indicateurs d'IBS chez les enfants âgés de moins de vingt-quatre mois. Etude descriptive monocentrique réalisée entre février 2009 et février 2010, au service d'Urgences Pédiatriques de l'Hôpital des enfants, Bordeaux, France. Les enfants fébriles de moins de vingt-quatre mois ayant consulté aux urgences ont été inclus dans l'étude. 1021 enfants sont inclus dans l'étude, la moyenne d'âge est de 12 mois ; elle comprend 54,7 % de garçons. 13 % des infections sont des infections bactériennes sévères. 38,8 % d'entre elles (n = 52) sont des infections bactériennes pulmonaires et 44 % (n = 59) sont pyélonéphrites. Le taux d'infections bactériennes sévères est plus élevé avant trois mois : 25 % avant un mois, 25 % entre un et trois mois et 7 % après trois mois. Le taux d'hémocultures positives est de 0,82 % (n = 2/242). Une fièvre > 40C doit faire éliminer une IBS (p = 3*10 puiss -4) de même qu'une résistance au traitement antipyrétique (p = 0,005). Ceci est particulièrement vrai pour les IBP. La cyanose, les marbrures, les frissons, la pâleur (p = 2,5* 10 puiss -4) sont présents à des taux supérieurs dans les pyélonaphrites (p 2 dérivations standard principalement (p = 0,007) puis, la cyanose et les frissons vrais (p 2 DS, bien que remise en cause par son manque de spécificité doit être contrôlée et prise en compte. Les signes de mauvaise circulation périphérique inclus dans "l'aspect toxique" traditionnellement décrit sont essentiellement la cyanose et la pâleur. Enfin les frissons vrais, s'ils ne sont pas constatés doivent être assidument expliqués puis recherchés lors de l'interrogatoire. La présence de ces signes justifie la réalisation d'examen complémentaire en cas de foyer infectieux non authentifié. Reste à inclure ces données dans une analyse multivariée pour renforcer leur significativité.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Allo-Immunisation transfusionnelle chez les enfants drépanocytaires (étude bi-centrique à Bordeaux et Créteil)

CONTEXTE : L'efficacité de la transfusion dans le traitement des complications aigues de la drépanocytose est connue depuis de nombreuses années. De nouvelles indications sous forme de programme transfusionnel ont récemment démontré leur intérêt en prévention primaire ou secondaire, notamment dans le cadre de l'AVC. Si le risque de transmission infectieuse au cours des transfusions semble aujourd'hui très limité, la question du risque d'allo-immunisation devient une préoccupation majeure, particulièrement dans les populations pédiatriques. Le but de notre étude est de mettre en évidence les facteurs de risque d'allo-immunisation transfusionnelle dans une cohorte d'enfants drépanocytaires. METHODES : Nous avons inclus 645 enfants drépanocytaires majeurs suivis entre septembre 1979 et décembre 2011 à Créteil et entre juin 1993 et décembre 2011 à Bordeaux. Les données cliniques, biologiques et transfusionnelles ont été recueillies de façon rétrospective. RESULTATS : 65 % des immunisations surviennent après des transfusions en contexte de complications aigues. Les facteurs de risque de l'allo-immunisation sont le nombre cumulé de transfusions (OR = 1,02[1,01 - 10 25], p < 0,001) et la présence d'auto-Ac (OR = 22[10,1 - 47,6], p < 0,001). Le génotype Be/Be apparaît inversement correlé au risque d'allo-immunisation (OR = 0,22 [0,07 - 0,66], p = 0,007). CONCLUSION : Notre étude met en évidence des situations transfusionnelles à risque chez les enfants drépanocytaires : contexte de complication aigue, d'un taux d'Hb bas ou existence d'un auto-Ac, situations dans lesquelles le bénéfice/risque de toute transfusion doit être mesuré et où le choix du sang transfusé devrait être discuté avec l'EFS. Le nombre cumulé de transfusion reste un facteur prédominant, d'où l'intérêt dans les années à venir de la promotion du don de sang dans les populations afro-antillaises permettant de limiter les différences antigéniques entre donneurs et receveurs.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Perception et représentations de la drépanocytose (enquête auprès de 26 familles suivies au CHU de Bordeaux)

OBJECTIFS : La perception d'une maladie chronique par le patient et son entourage influence le vécu psychologique de celle-ci et l'adhésion aux soins. Cette thèse se propose d'étudier la perception de la drépanocytose, ses représentations et leurs liens avec l'observance. METHODES : Nous avons adapté l'Illness Perception Questionnaire joint à une échelle d'évaluation de l'observance au cas particulier de la drépanocytose. Nous avons étudié la relation de cette perception avec les facteurs de migration, de dépression et de gravité de la maladie au sein d'une population de 26 familles suivies pour drépanocytose à l'Hôpital des Enfants de Bordeaux. Une analyse qualitative des entretiens avec les familles ainsi que l'étude d'autoportraits en période de crise douloureuse réalisés par des enfants drépanocytaires ont été associées à cette recherche. RESULTATS : Une symptomatologie dépressive ou l'existence de critères de gravité semblent avoir une influence négative sur la perception de la drépanocytose. La migration a une influence hétérogène sur cette perception. Concernant les causes perçues de la maladie et les thérapeutiques employées, les modèles traditionnels et biomédicaux coexistent dans la majorité des cas. Le retentissement émotionnel et psychologique de la maladie chez les enfants est majeur mais il est souvent sous-estimé par les parents. Les conséquences sur la vie sociale de toute la famille sont notables. CONCLUSION : La rencontre et le besoin d'échanges avec d'autres familles atteintes semblent essentiels pour pallier au sentiment d'isolement. Des groupes de parole et d'éducation thérapeutique permettraient de faciliter les relations familles-soignants et de dépister d'éventielles difficultés psychologiques chez les enfants.BACKGROUND : The perception of a chronic illness by the patient and his family influences psychological issues and treatment adherence. The aim of this research is to study sickle-cell disease perception, its associated representations and their relation to treatment adherence. METHODS : We adapted the Illness Perception Questionnaire to sickle-cell disease associated with an adherence scale and studied its relationship with migration, depression and disease severity in a popoulation of 26 families followed-up in the Children's Hospital of Bordeaux, France. A qualitative analysis of families'interviews and the study of self-portraits in painful episodes, drawn by sickle-cell children, have also been described. RESULTS : Depression and disease severity may have a negative influence upon the illness perception whereas migration has an heterogeneous influence upon it. In the majority of cases, traditional and biomedical models co-exist in understanding the illness and its treatment. The emotional and psychological impact due to the disease is important for children but seems often underestimated by their parents. The consequences on the social life of the whole family are notable. CONCLUSION : Family meetings and exchanges between patients seem essential to overcome the feeling of isolation. Support and educative groups could facilitate relationships between family and caregivers and identify potential difficlties among children.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Clinical, virological and immunological features of HIV-positive children internationally adopted in France from 2005-2015.

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

Prevalence and clinical outcomes of poor immune response despite virologically suppressive antiretroviral therapy among children and adolescents with human immunodeficiency virus in Europe and Thailand: Cohort study

Background. In human immunodeficiency virus (HIV).positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods. Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children <18 years at ART initiation, with sustained viral suppression (VS) (.400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. Results. Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P < .001). Conclusions. One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders

Rilpivirine in HIV-1-positive women initiating pregnancy: to switch or not to switch?

International audienceBackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.ObjectivesTo describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.MethodsIn the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC.ResultsAmong 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred.ConclusionsIn virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes

Children living with HIV in Europe: do migrants have worse treatment outcomes?

International audienceTo assess the effect of migrant status on treatment outcomes among children living with HIV in Europe

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

International audienceIn human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART