Bictegravir/emtricitabine/tenofovir alafenamide in paediatrics: Real-life experience from a French cohort (2019-2023).

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.

Similar efficacy and safety of dolutegravir between age groups of HIV-1-infected paediatric and young adult patients aged 5 years and older.

OBJECTIVES: The aim of the study was to carry out a comparison of the safety and efficacy of dolutegravir-based regimens among age groups of HIV-1-infected paediatric and young adult patients. PATIENTS AND METHODS: This retrospective monocentric study included 109 patients infected since childhood who began receiving dolutegravir between January 2014 and December 2017. The patients were divided into three groups according to age at the time of dolutegravir initiation: 5-11, 12-17 and 18-25 years old. The primary endpoint was the proportion of patients achieving a plasma viral load (PVL) < 50 HIV-1 RNA 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: Most of the subjects were antiretroviral-experienced (91.7%) and virologically suppressed at baseline (66.7%, 54.9% and 56.0% in the 5-11, 12-17 and 18-25 year age groups, respectively). Median follow-up was 24 months (range 6-54 months). Sustained virological success throughout follow-up was observed in 79.8% of patients, with similar rates among age groups (87.9%, 72.5% and 84.0%, respectively; P = 0.22). With reinforced measures to improve adherence, undetectable PVL was obtained at the last visit in 88.1% of patients, with similar proportions among age groups (93.9%, 84.3% and 88.0%, respectively; P = 0.51). No emergence of resistance mutations was observed in the 22 patients with virological failure. Dolutegravir was well tolerated; only one patient stopped treatment for severe drug-related side effects. CONCLUSIONS: The virological efficacy and safety of dolutegravir were similar among the three age groups. Because of its high genetic barrier to resistance, dolutegravir could be especially useful in the paediatric population, in which the risk of poor treatment adherence is high.

High rates of antiretroviral coverage and virological suppression in HIV-1-infected children and adolescents.

OBJECTIVES: To assess the outcome of HIV-infected individuals attending one of the largest French pediatric HIV centers in 2016-2017 and to compare the rates of antiretroviral coverage and virological suppression with the UNAIDS targets. PATIENTS AND METHODS: The clinical and immuno-virological status of 163 HIV-1-infected children and adolescents attending Necker Hospital in Paris, France, were investigated. Virological suppression was defined as an HIV-1 viral load<50 copies/mL for at least six months. All genotypic resistance tests performed since birth were analyzed. RESULTS: Most patients were born in Sub-Saharan African countries (41.7%) or in France (38.0%). Their median age was 14 years [IQR 7.3-17.0]. Although 33.7% of individuals had a history of AIDS-defining clinical event(s), 86.5% of children/adolescents were free from HIV-related symptoms at their most recent evaluation. Antiretroviral coverage was high (98.2%; mainly including one integrase inhibitor [42.3%] or one protease inhibitor [23.9%]). At the last visit, most patients (82.8%) had normal CD4T lymphocytes counts (≥25%). Although 61.7% of antiretroviral-experienced children had resistance to≥1 drug class and 9.2% had triple-class resistance, 80.3% of patients receiving antiretrovirals for≥6 months (126/157) were virologically suppressed. International adoptees were more frequently virologically suppressed than other patients (96.0% versus 74.6%, P=0.02). CONCLUSIONS: Antiretroviral coverage exceeded the second UNAIDS 90 target aimed at ending the AIDS epidemic. The rate of virological suppression, one of the highest reported in children in high-income countries, is approaching the third UNAIDS 90 target and the rate observed in French HIV-infected adults on antiretrovirals.

Bacillus Calmette-Guérin infection after vaccination of human immunodeficiency virus-infected children.

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.

Chondrosarcoma of the larynx.

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.

[Metastatic cervical adenopathies appearing as primary. A propos of 124 cases]. / Les adénopathies cervicales métastatiques primitives en apparence. A propos de 124 cas.

The authors are defining the significance of a metastatic neck node from an occult carcinoma and review all the necessary investigations including surgical neck exploration and frozen section to establish the diagnosis. In such a case a radical neck dissection is carried out without delay and postoperative radiotherapy is applied on the neck with special portals focused on the pharyngo-larynx area where any possible infraclinic tumor might be located. The occult primary may become clinically detectable after a variable time interval, this occurrence is rather rare and becomes exceptional when irradiation has been delivered on the neck after surgical exploration. A high incidence of distant metastases is noticed during the follow-up period. The long term prognosis of metastatic cervical lymph node is rather poor and depends in particular of the size of the involved node.

[Acquired and constitutional neutropenia in children]. / Neutropénies constitutionnelles et acquises de l'enfant.

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.

[Infection of the newborn infant by the human immunodeficiency virus]. / L'infection du nouveau-né par le virus de l'immunodéficience humaine.

HIV infection of the newborn is now known to result mostly from mother-to-foetus transmission. The risk of transmission is at least 40 p. 100. However, the circumstances of passage are little known, and there is no maternal virological parameter capable of evaluating individual risks. The disease is more severe in children than in adults. Rare are the children who remain asymptomatic for more than 15 months; one out of three of them develop severe acquired immunodeficiency syndrome and die within the first 2 or 3 years of life. A specific encephalopathy is observed in about 30 p. 100 of the infected children. Kaposi's sarcoma is exceptional. Since there is no contagion between children, those who are in fairly good clinical condition should have a family and school life as normal as possible.

[Purulent meningitis after minor nasosinus surgery. Apropos of 10 cases]. / Méningites purulentes après chirurgie naso-sinusienne banale. A propos de 10 cas.

Purulent meningitis developed during the immediate or late postoperative period in 10 patients undergoing minor surgical procedures for nasosinusal affections. An important point is that the meningeal infection may be a very late onset complication, the osteodural gap sometimes giving rise to several attacks of meningitis at unexpected times. Treatment should be based on the presence or absence of clinical cerebrospinal fluid rhinorrhea, of a fracture of the anterior shelf of base of cranium on tomography, and results of isotopic scanning which are valid only if positive. Surgery to close the gap is justified when rhinorrhea persists after recovery from meningitis or when recurrent bouts are reported. Even after surgery, however, there is still the risk of further attacks of meningitis. An interesting adjuvant to treatment is by antipneumococcal vaccination.

[Medical treatment of laryngotracheal stenosis (author's transl)]. / Traitement médical des sténoses laryngo-trachéales.

The authors review the various types of treatment involving drugs and physical agents used for the non-surgical therapy of laryngotracheal stenosis. They emphasize three interesting propositions: the use of zinc sulphate, of lathyrogens and muscle relaxants, an extensive experimental study of which would be worthwhile in the particular context of laryngotracheal stenosis.

[Postoperative infection in ORL oncologic surgery. The choice of preventive antibiotherapy. Experience of the ORL Department of Hôpital Claude Bernard]. / L'infection postopératoire en chirurgie carcinologique ORL. Le choix de l'antibiothérapie prophylactique. L'expérience du Service ORL de l'Hôpital Claude Bernard.

The incidence of infection after cervicofacial surgery for ENT cancer varied between 38 and 60% as a function of the type of operation, and prophylactic antibiotic therapy administered, in a series of 133 cases. Contamination was greatest after operations of longest duration and with the largest exposure of tissue. Previous cobalt therapy was an aggravating factor. The highest risk of infections complications resulted therefore from combined salvage operations and the use of a musculocutaneous flap. Among these infections, a purulent bronchorrhea was a frequent and potentially serious complication sometimes the cause of septicemia. A review of 4 different antibiotic therapy regimens showed the pre-operative administration failed to alter the outcome. Combined penicillin-5 imidazole treatment, effective in preventing local and regional anaerobic infection, resulted in secondary infection developing in about 56% of cases. It was not able, in fact, to cover under certain circumstances during prolonged surgery, the postoperative risk of inhalation of gram-negative anaerobic and aerobic bacteria form the buccal cavity. Short-term antibiotic therapy was totally ineffective. It is suggested that combined penicillin-5 imidazole be reserved for operations provoking little contamination of the tracheobronchial region, such as total laryngectomy and total pharyngo-laryngectomy, and that prophylactic therapy using an antibiotic with a wide spectrum against gram negative germs be administered prior to major buccopharyngeal operations with tracheotomy.

[Ethmoidal fibroma in an 18-month-old infant (author's transl)]. / Fibrome ethmoïdal chez un nourrisson de 18 mois.

A case of ethmoidal fibroma in an 18-month-old infant is reported, and nosological, histological, and pathogenic features of this rare affection discussed. Though similar in some respects to Jaffe Lichtensteins fibrous dysplasia in its localized form, it differs, in that it sometimes runs a rapid course and has a tendency to relapse.

[Value of manubriotomy in extensive thyroid surgery. 11 cases (author's transl)]. / Intérêt de la manubriotomie dans la chirurgie extensive du corps thyroïde. A propos de 11 cas.

Manubriotomy was performed in 11 cases of retrosternal goitre or extensive thyroid cancers. The advantages of this method, which is described in detail, are that sternotomy can be avoided in the majority of cases, and that the postopeuative period is particularly straightforward.

[Survival of bone after osteomuscular transposition. Histological study in man and an experimental model]. / La survie de l'os après transposition ostéomusculaire. Etude histologique chez l'homme et sur un modèle expérimental.

Most bone cells in homografts fail to survive, and several months are required before live bone tissue structures develop in the graft. Various attempts have been made to preserve or re-establish homograft vascularization. One method involves the use of free bone transfer with revascularization of the supply artery or the total periosteal network, this enabling the majority of the bone cells to survive. Another procedure uses osteomuscular transplants in which the muscle acts as a pedicle for the transplanted bone segment, but whether bone elements in these flaps remain viable is a very debatable point. Experimental and clinical studies were conducted to evaluate, histologically, the viability of bone after osteomuscular transplantation. Fluorescence examination of bone sections from 40 osteomuscular flaps in the rat demonstrated bone formation on the external cortical surface but marked diminution of endosteal moulding in other zones. Examination of bone biopsies from 10 patients treated by mandibular reconstitution using an osteomuscular flap provided data comparable with those obtained during the experimental study. These findings demonstrate that osteomuscular transplantation is responsible for endosteal ischemia, preventing survival of cells other than those lying most externally to the cortex.

[Velopharyngeal rehabilitation after transmaxillary buccopharyngectomy extending to the soft palate]. / Réhabilitation vélo-pharyngée après bucco-pharyngectomie-transmaxillaire élargie à la région vélo-palatine.

Two types of velopharyngeal rehabilitation are proposed after transmaxillary buccopharyngectomy extending to the soft palate region. The first method is by velopharyngoplasty, when exeresis has not involved a half or a quarter of the soft palate and at least half of the posterior pharyngeal wall. The second procedure is for use after exeresis involving all or almost all of the soft palate and a half of the posterior pharyngeal wall, and makes use of velum palatinum reconstruction. The method of choice is velopharyngoplasty, excellent functional results being obtained for both phonation and feeding.

[Total glossectomy with preservation of the larynx and immediate reconstruction. Apropos of 27 cases]. / Glossectomies totales avec préservation du larynx et reconstruction immédiate. A propos de 27 cas.

Total glossectomy with preservation of larynx was performed in 27 patients with lesions affecting the whole tongue and developing from the base, the tonsilloglottal recess, of the junction zone and of the posterior wall, or from the mobile tongue. Results in patients followed up for more than one year (27 cases) showed: 11 survivors only, with 12 deaths from local, regional or metastatic recurrence. Among the 11 survivors, 7 presented very satisfactory functional rehabilitation--they no longer required tracheotomies, were free from pain and fed themselves without problem with mixed types of food. Phonation could be understood and they were reasonably autonomous. When tumoral excision is possible in patients with extension not evident as palpable glands, this operation appears quite justified for patients who are psychologically motivated and very insistent on some therapy, the modalities and risks of which have been exposed.

[Surgery of pericannular recurrence and extensive tumors of the trachea]. / La chirurgie des récidives péri-canulaires et des tumeurs étendues de la trachée.

Treatment proposed for pericannular recurrence and previously irradiated vast, extensive, subglottotracheal tumors involves the performance of a manubriectomy with reconstruction using a musculocutaneous flap. The former solves the problem of the route of approach and local carcinologic safety and the latter provides a solution to the problem of congruence of trachea and presternal teguments as well as postoperative complications by protecting the brachiocephalic arterial trunk.

[Five cases of pharyngeal tuberculosis seen over a period of one year (author's transl)]. / A propos de cinq cas de tuberculose pharyngée observés en un an.

The authors report five cases of pharyngeal tuberculosis seen over a period of one year and which were all, with one exception, surprise histological findings. Such histological findings were not always completely specific and the diagnosis was confirmed by a strongly positive tuberculin skin reaction, pulmonary disease and, above all, the elimination of symptoms and physical signs in less than 3 weeks under the influence of specific antituberculous therapy.

[Mandibular reconstruction by composite musculocutaneous flap in glossopelvimandibular excisions]. / La reconstruction mandibulaire par lambeau musculo-cutané composé dans les exérèses glosso-pelvi-mandibulaires.

Results of 14 mandibular reconstruction by a composite muscular flap of the pectoralis major and trapezium muscles during widespread glossopelvimandibular excisions are described. The technique employed is outlined, emphasis being placed on the need to observe strict precautions during removal and application of the bone component, to avoid accidental avulsion during reconstruction which could compromise the musculoperiosteal vascularization of the graft. Results are sufficiently encouraging for this type of reconstructive surgery to be proposed in all cases where mandibular repair is necessary after interruption of continuity.