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1.
Front Immunol ; 12: 662894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968064

RESUMO

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/CD8TN), 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 CD8TN percentages (medians: 48.7% vs. 31.0%, P = 0.001), and a marginally higher CD4TN (61.2% vs. 53.1%, P = 0.33). In adolescents, early ART was associated with low CD4TN percentages and less differentiated memory CD8 T cells. CD4TN and CD8TN levels were inversely related to cellular activation and gut permeability. Conclusion: In children and adolescents, the benefits of early ART for CD8TN were clear after long-term ART. The impact of early ART on CD4TN appears to be modest, because pediatric patients treated late respond to HIV-driven CD4 T-lymphocyte loss by the de novo production of TN cells in the thymus. Our data also suggest that current immune activation and/or gut permeability has a negative impact on TN levels. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02674867.


Assuntos
Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adolescente , Linfócitos T CD4-Positivos/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Ativação Linfocitária , Contagem de Linfócitos , Masculino , Tempo para o Tratamento
2.
Pediatr Infect Dis J ; 40(4): 344-346, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33710978

RESUMO

Eleven newborns from 25 to 32 weeks of gestational age, weighting from 0.66 to 1.60 kg received 2 mg/kg doses of nevirapine syrup. In 15 samples, collected 8.75-89 hours after drug intake, concentrations ranged from 0.65 to 16.68 mg/L. Three nevirapine dose of 2 mg/kg at day 0, 2 and 6 days of life achieved nevirapine concentrations above the proposed nevirapine target for HIV prophylaxis for at least 11 days.


Assuntos
Fármacos Anti-HIV/farmacocinética , Idade Gestacional , Infecções por HIV/prevenção & controle , HIV-1/efeitos dos fármacos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Nevirapina/farmacocinética , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , Administração Oral , Fármacos Anti-HIV/administração & dosagem , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Recém-Nascido , Nevirapina/administração & dosagem , Gravidez
3.
Eur J Clin Microbiol Infect Dis ; 40(1): 133-140, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32812077

RESUMO

To identify factors associated with vaginal colonization and persistence by group B Streptococcus (GBS) and by the hypervirulent neonatal CC-17 clone in late pregnancy and after delivery, a multicentre prospective observational cohort with 3-month follow-up was established in two university hospitals, Paris area, France. Pregnant women were recruited when antenatal screening for GBS vaginal colonization at 34-38 weeks of gestational age was positive. Vaginal samples were analysed by conventional culture methods at antenatal screening, delivery, and 21 and 60 days following delivery. Identification of the hypervirulent neonatal GBS CC-17 was performed. Colonization was defined as persistent when all vaginal samples were positive for GBS. A total of 754 women were included. GBS vaginal colonization was persistent in 63% of the cases (95% CI 59%-67%). Persistent colonization was more likely in women born in Sub-Saharan Africa compared with women born in France (OR = 1.88, 95% CI 1.05-3.52), and GBS CC-17 was overrepresented in women born in Sub-Saharan Africa (OR = 2.09, 95% CI 1.20-3.57). Women born in Sub-Saharan Africa are at higher risk for GBS vaginal persistence than women born in France. This observation correlates with an increased prevalence of the hypervirulent GBS CC-17 in the former group, which likely reflect variations linked to ethnicity and vaginal community-state types and might account for the increased susceptibility of black neonates to GBS infections.


Assuntos
Complicações Infecciosas na Gravidez/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae/patogenicidade , Doenças Vaginais/epidemiologia , Adolescente , Adulto , Células Clonais , Estudos de Coortes , Emigrantes e Imigrantes , Feminino , França/epidemiologia , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/etnologia , Complicações Infecciosas na Gravidez/microbiologia , Cuidado Pré-Natal , Prevalência , Estudos Prospectivos , Infecções Estreptocócicas/etnologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/genética , Doenças Vaginais/etnologia , Doenças Vaginais/microbiologia , Adulto Jovem
4.
Clin Infect Dis ; 69(10): 1740-1748, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30946447

RESUMO

BACKGROUND: In infants, the mode of acquisition of CC17 group B Streptococcus (GBS), the hypervirulent clone responsible for late-onset disease (LOD), remains elusive. METHODS: In a prospective multicenter study in France, we evaluated GBS colonization in mother-baby pairs with 2 months of follow-up between 2012 and 2015. Criteria included positivity for GBS colonization at antenatal screening or at delivery. Maternal vaginal samples and infant oral cavity and stool samples were analyzed at delivery, 21 ± 7 days (D21), and 60 ± 7 days (D60) post-delivery. RESULTS: A total of 890 mother-baby pairs were analyzed. GBS colonized 7%, 21%, and 23% of the infants at birth, D21, and D60, respectively, of which 10%, 11%, and 13% were identified as CC17 GBS. Concordance between maternal and infant GBS type was 96%. At D21, the main risk factors for infant colonization by GBS were simultaneous maternal colonization of the vagina (odds ratio [OR], 4.50; 95% confidence interval [CI], 1.69-15.61) and breast milk (OR, 7.93; 95% CI, 3.81-17.14). Importantly, 38% (95% CI, 23%-56%) of infants colonized by CC17 GBS appeared colonized for the first time at D60 vs 18% (95% CI, 14%-24%; P < .049) of infants colonized by non-CC17 GBS. Multivariate analysis showed a higher risk for de novo infant colonization by CC17 at D60 than by other GBS (OR, 2.45; 95% CI, 1.02-5.88). CONCLUSIONS: The high incidence of CC17 GBS in LOD is likely due to an enhanced post-delivery mother-to-infant transmission.


Assuntos
Transmissão Vertical de Doenças Infecciosas , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/patogenicidade , Adulto , Fezes/microbiologia , Feminino , França , Humanos , Incidência , Lactente , Estudos Longitudinais , Masculino , Mães , Boca/microbiologia , Gravidez , Estudos Prospectivos , Fatores de Risco , Streptococcus agalactiae/genética , Vagina/microbiologia , Virulência
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