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1.
Medicine (Baltimore) ; 99(9): e19353, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118776

RESUMO

Pneumococcal nasopharyngeal colonization is a pre-requisite for pneumococcal disease; the risk for pneumococcal disease is high in children born to women living with human immunodeficiency virus (HIV). We investigated pneumococcal colonization, serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae isolates carried by perinatal HIV-infected and HIV-exposed-uninfected (HEU) children.Serial nasopharyngeal swabs were collected from 331 HIV-infected and 491 HEU children, at up to 6 scheduled timepoints, between median ages of 25 to 181 weeks. Pneumococcus was identified by culture; serotyping and antibiotic susceptibility testing were done by conventional methods. No pneumococcal vaccine was given.HIV-infected children were less likely to be colonized with 7-valent pneumococcal conjugate vaccine 7 serotypes than HEU at a median of 25 weeks of age (23% vs 36%; P < .001); however, no differences in colonization between the 2 groups were observed at subsequent study-visits. Over the 36-months study-period pneumococcal colonization increased in both HIV-infected (from 45% to 77%) and HEU (from 57% to 61%) children. Over the study-period, pneumococcal isolates non-susceptible to cotrimoxazole decreased from 92% to 57% and had a similar trend to penicillin (from 65% to 42%) in HIV-infected children. Similarly, pneumococcal nonsusceptible to cotrimoxazole decreased from 93% to 57% and to penicillin from 69% to 37% in HEU children.Vaccine serotype colonization was common in this population and similar rates were observed in HIV-infected and HEU children. The prevalence of pneumococcal isolates non-susceptible to cotrimoxazole and penicillin decreased with age.


Assuntos
Infecções por HIV/virologia , Infecções Pneumocócicas/diagnóstico , Streptococcus pneumoniae/patogenicidade , Adolescente , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Lactente , Vacinas contra Influenza/uso terapêutico , Masculino , Líquido da Lavagem Nasal/microbiologia , Infecções Pneumocócicas/epidemiologia , Prevalência , África do Sul/epidemiologia
2.
Clin Infect Dis ; 63(8): 1113-1121, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27439527

RESUMO

BACKGROUND: The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1060 study demonstrated short-term superiority of lopinavir/ritonavir (LPV/r) over nevirapine (NVP) in antiretroviral therapy (ART), regardless of prior NVP exposure. However, NVP-based ART had a marginal benefit in CD4 percentage (CD4%) and growth. We compared 5-year outcomes from this clinical trial. METHODS: Human immunodeficiency virus (HIV)-infected, ART-eligible children were enrolled into 2 cohorts based on prior NVP exposure and randomized to NVP- or LPV/r-based ART. The data safety monitoring board recommended unblinding results in both cohorts due to superiority of LPV/r for the primary endpoint: stopping randomized treatment, virologic failure (VF), or death by 6 months. Participants were offered a switch in regimens (if on NVP) and continued observational follow-up. We compared time to VF or death, death, and CD4% and growth changes using intention-to-treat analyses. Additionally, inverse probability weights were used to account for treatment switching and censoring. RESULTS: As of September 2014, 329 of the 451 (73%) enrolled participants were still in follow-up (median, 5.3 years; interquartile range [IQR], 4.3-6.4), with 52% on NVP and 88% on LPV/r as originally randomized. NVP arm participants had significantly higher risk of VF or death (adjusted hazard ratio [aHR], 1.90; 95% confidence interval [CI], 1.37-2.65) but not death alone (aHR, 1.65; 95% CI, .72-3.76) compared with participants randomized to LPV/r. Mean CD4% was significantly higher in the NVP arm up to 1 year after ART initiation, but not beyond. Mean weight-for-age z scores were marginally higher in the NVP arm, but height-for-age z scores did not differ. Similar trends were observed in sensitivity analyses. CONCLUSIONS: These findings support the current World Health Organization recommendation of LPV/r in first-line ART regimens for HIV-infected children. CLINICAL TRIALS REGISTRATION: NCT00307151.


Assuntos
Infecções por HIV/tratamento farmacológico , Lopinavir/uso terapêutico , Nevirapina/uso terapêutico , Ritonavir/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Pré-Escolar , Feminino , Seguimentos , Infecções por HIV/diagnóstico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Índice de Gravidade de Doença , Falha de Tratamento , Resultado do Tratamento , Carga Viral
3.
AIDS ; 27(3): 369-79, 2013 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-23032417

RESUMO

BACKGROUND: HIV-infected children are at heightened risk for severe influenza illness; however, there is no study on the efficacy or effectiveness of influenza vaccine in these children. We evaluated the safety, immunogenicity, and efficacy of nonadjuvanted, trivalent inactivated influenza vaccine (TIV) against confirmed seasonal influenza virus illness in HIV-infected children. METHODS: A double-blind, placebo-controlled trial was undertaken in Johannesburg in 2009. Four hundred and ten children were randomized to two doses of TIV or placebo 1 month apart. Nasopharyngeal aspirates obtained at respiratory illness visits were tested by influenza-specific reverse transcriptase-PCR (RT-PCR). Vaccine immunogenicity was evaluated by hemagglutinin inhibition (HAI) assay. Influenza isolates were sequenced and evaluated in maximum likelihood phylogenetic analysis. RESULTS: Overall, the median age of participants was 23.8 months and their median CD4% was 33.5. Ninety-two percent of enrolees were on antiretroviral therapy. Among children receiving both doses of vaccine/placebo, confirmed seasonal influenza illness occurred in 13 (all H3N2) of 205 TIV recipients and 17 (15 H3N2 and two influenza B) of 200 placebo recipients with vaccine efficacy of 17.7% (95% confidence interval <0-62.4%). The proportion of TIV recipients who seroconverted after second dose against vaccine strains of H1N1, H3N2, and influenza B were 47.5, 50.0, and 40.0%, compared to 4.7, 11.6, and 0%, respectively among placebo recipients. There were no TIV-related serious adverse events. Sequence analysis of wild-type H3N2 strains indicated drift from the H3N2 vaccine strain. CONCLUSION: Poor immunogenicity of TIV, coupled with drift of circulating H3N2 wild-type compared to vaccine strain, may explain the lack of efficacy of TIV in young HIV-infected children. Alternate TIV vaccine schedules or formulations warrant evaluation for efficacy in HIV-infected children.


Assuntos
Anticorpos Antivirais/imunologia , Soropositividade para HIV/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Pneumonia/imunologia , Contagem de Linfócito CD4 , Pré-Escolar , Método Duplo-Cego , Feminino , Seguimentos , Soropositividade para HIV/epidemiologia , Testes de Inibição da Hemaglutinação , Hospitalização , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza A/imunologia , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/imunologia , Vírus da Influenza B/isolamento & purificação , Vacinas contra Influenza/administração & dosagem , Influenza Humana/epidemiologia , Influenza Humana/virologia , Masculino , Filogenia , Pneumonia/epidemiologia , Pneumonia/virologia , África do Sul/epidemiologia , Resultado do Tratamento , Eliminação de Partículas Virais
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