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1.
N Engl J Med ; 381(14): 1333-1346, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31577875

RESUMO

BACKGROUND: The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS: In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS: A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Tuberculose/prevenção & controle , Adolescente , Adulto , Antituberculosos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Isoniazida/efeitos adversos , Testes de Função Hepática , Período Pós-Parto , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Adulto Jovem
2.
Pediatr Infect Dis J ; 36(1): 53-60, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27749649

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) have increased prevalence of hyperlipidemia and risk factors for cardiovascular disease. No studies have investigated the efficacy and safety of statins in this population. METHODS: HIV-infected youth 10 to <24 years of age on stable ART with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL for ≥6 months initiated atorvastatin 10 mg once daily. Atorvastatin was increased to 20 mg if LDL-C efficacy criteria (LDL-C < 110 mg/dL or decreased ≥30% from baseline) were not met at week 4. Primary outcomes were safety and efficacy. RESULTS: Twenty-eight youth initiated atorvastatin; 7 were 10-15 years and 21 were 15-24 years. Mean baseline LDL-C was 161 mg/dL (standard deviation 19 mg/dL). Efficacy criteria were met at week 4 by 17 of 27 (63%) participants. Atorvastatin was increased to 20 mg in 10 participants. Mean LDL-C decreased from baseline by 30% (90% confidence interval: 26%, 35%) at week 4, 28% (90% confidence interval: 23%, 33%) at week 24 and 26% (90% confidence interval: 20%, 33%) at week 48. LDL-C was less than 110 mg/dL in 44% at week 4, 42% at week 12 and 46% at weeks 24 and 48. Total cholesterol, non high-density lipoprotein (non-HDL)-C and apolipoprotein B decreased significantly, but IL-6 and high-sensitivity C-reactive protein did not. Two participants in the younger age group discontinued study for toxicities possibly related to atorvastatin. CONCLUSIONS: Atorvastatin lowered total cholesterol, LDL-C, non HDL-C and apolipoprotein B in HIV-infected youth with ART-associated hyperlipidemia. Atorvastatin could be considered for HIV-infected children with hyperlipidemia, but safety monitoring is important particularly in younger children.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Atorvastatina/efeitos adversos , Atorvastatina/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hiperlipidemias/complicações , Adolescente , Adulto , Proteína C-Reativa/análise , Criança , Feminino , Humanos , Masculino , Adulto Jovem
3.
Pediatr Infect Dis J ; 35(1): e12-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26741589

RESUMO

BACKGROUND: Limited empirical investigation exists into longitudinal changes in cognition, behavior or quality of life (QOL) in children with perinatal HIV who are prescribed stimulants. METHODS: This study was an analysis of longitudinal data from children age 3-19 years, with perinatal HIV infection, with and without prescriptions for stimulant medications [prescription (PG) and comparison (CG) groups, respectively], matched on age, availability of CD4% and outcome measures of cognition, behavior and QOL. Generalized estimating equation models were used to evaluate effects of stimulant exposure on change in measured outcomes over 3 years of follow-up, adjusting for baseline levels of outcomes and relevant covariates. RESULTS: Children in both the PG (n = 132) and the CG (n = 392) obtained mean verbal and performance (nonverbal) intelligence quotients (VIQ and PIQ, respectively) in the low-average range for age. At baseline, those in PG demonstrated more frequent signs of hyperactivity, impulsivity and conduct and learning problems than those in CG (P ≤ 0.003 in unadjusted analyses). At follow-up, after adjustment for baseline functioning and other relevant covariates, there were no significant changes from baseline in VIQ or PIQ. Stimulant prescription use, however, was associated with worsening symptoms of hyperactivity (P = 0.01), impulsivity (P = 0.04), learning problems (P < 0.001) and worsening of perceived health status (P < 0.001). CONCLUSIONS: The results suggest expectations for behavioral improvement may not align well with long-term effects of stimulant prescription use on behavior and QOL in children with HIV. Further research is necessary to determine if there are subsets of children who may benefit from stimulant therapy.


Assuntos
Comportamento , Estimulantes do Sistema Nervoso Central , Cognição , Prescrições de Medicamentos , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Qualidade de Vida , Adolescente , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estimulantes do Sistema Nervoso Central/administração & dosagem , Criança , Pré-Escolar , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Vigilância da População , Carga Viral , Adulto Jovem
4.
PLoS One ; 10(3): e0120474, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25794163

RESUMO

BACKGROUND: We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study. METHODS: Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. RESULTS: Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. CONCLUSIONS: In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.


Assuntos
Terapia Antirretroviral de Alta Atividade , Coinfecção , Infecções por Citomegalovirus/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Contagem de Linfócitos , Subpopulações de Linfócitos T/imunologia , Adolescente , Antígenos CD/metabolismo , California , Criança , Pré-Escolar , Infecções por Citomegalovirus/virologia , Feminino , Infecções por HIV/virologia , Humanos , Imunidade Celular , Imunofenotipagem , Lactente , Ativação Linfocitária/imunologia , Masculino , Resultado do Tratamento , Carga Viral
5.
J Pediatr Psychol ; 38(6): 664-74, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23629146

RESUMO

OBJECTIVE: To apply a social ecological model to explore the psychosocial factors prospectively associated with longitudinal adherence to antiretroviral treatment in youth perinatally infected with HIV. METHODS: Randomly selected youth, age 8 to <19 years old, completed cognitive testing and psychosocial questionnaires at baseline as part of a multisite protocol (N = 138). A validated caregiver-report measure of adherence was completed at baseline and 24 and 48 weeks after baseline. RESULTS: In multivariate analysis, youth awareness of HIV status, caregiver not fully responsible for medications, low caregiver well-being, adolescent perceptions of poor caregiver-youth relations, caregiver perceptions of low social support, and African American ethnicity were associated with nonadherence over 48 weeks. CONCLUSIONS: Interventions focusing on caregivers and their interactions with the individual youth and extrafamilial system should be prioritized for prevention and treatment efforts to address nonadherence during the transition into adolescents.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Adolescente , Cuidadores/psicologia , Criança , Feminino , Infecções por HIV/psicologia , Soropositividade para HIV , Humanos , Estudos Longitudinais , Masculino , Inquéritos e Questionários
6.
AIDS ; 26(8): 959-69, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22382148

RESUMO

OBJECTIVE: To evaluate baseline T-cell activation and neurodevelopmental outcomes over time in a cohort of perinatally HIV-infected (PHIV-infected) children with severe disease. DESIGN: Pediatric AIDS Clinical Trials Group protocol 366 (PACTG 366) was a partially randomized, open-label, multicenter 96-week antiretroviral treatment-algorithm study. Neurodevelopmental status, measured by age-dependent evaluations (Bayley scales of infant development-II; Wechsler preschool and primary scale of intelligence-revised; Wechsler intelligence scale for children-III), was a secondary outcome. METHODS: Linear mixed models were used to assess the baseline and follow-up neurodevelopmental outcomes in relation to immune activation, measured by CD38 and human leukocyte antigen (HLA) DR expression on peripheral CD4(+) and CD8(+) T cells at study baseline. Models were adjusted for age, sex, race/ethnicity, baseline viral load, baseline CD4%, cytomegalovirus (CMV) infection status at entry, study treatment arms, central nervous system penetrance score of antiretroviral regimen at entry, and viral load response 16 weeks postentry. RESULTS: Among 126 PACTG 366 enrollees who were at least 1 year old and had both immune activation and age-appropriate neurodevelopmental assessments at baseline, 80 (63%) were black non-Hispanic, 71 (56%) males, 122 (97%) were on antiretrovirals, and 45 (36%) were in Centers for Disease Control and Prevention (CDC) disease category C at entry. CD4(+)CD38(+)HLADR(+)%, CD4(+)CD38(-)HLADR(+)%, and CD8(+)CD38(+)HLADR(+)% were positively associated with full-scale Intelligence Quotient scores (FSIQ) (slope = 0.18, 0.70, and 0.15, respectively; P = 0.02, 0.03, and 0.04, respectively). CD4(+)CD38(+)HLADR(-)% was negatively associated with FSIQ (slope =  -0.16, P = 0.01). CONCLUSION: Contrary to HIV-infected adults, in PHIV-infected children higher CD4(+)CD38(+)HLADR(+)% may be associated with a neuroprotective effect and higher percentage of CD4(+)CD38(+) but HLADR(-) T cells may be deleterious.


Assuntos
Doenças do Sistema Nervoso Central/complicações , Infecções por HIV/complicações , ADP-Ribosil Ciclase 1/metabolismo , Adolescente , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Criança , Pré-Escolar , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Antígenos HLA/metabolismo , Humanos , Lactente , Masculino , Fatores de Tempo
7.
Neurobehav HIV Med ; 2010(2): 39-48, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20865061

RESUMO

PURPOSE: Perinatally HIV-infected children, who are increasingly aging into adolescence and early adulthood, have significant rates of psychiatric co-morbidities, some of which are treated with second-generation antipsychotics (SGAs). SGAs have been associated with elevated total cholesterol (TC) in youth, but no studies have examined this association in perinatally HIV-infected youth. This study examined changes in TC levels of youth with perinatally acquired HIV infection and co-morbid psychiatric conditions treated with SGAs. PATIENTS AND METHODS: Long-term changes in TC levels were examined using data from the US multisite prospective Pediatric AIDS Clinical Trials Group 219C cohort study. The change in TC levels from baseline to 12 months after initiating SGA use was compared between 52 SGA-exposed and 148 matched SGA-unexposed perinatally HIV-infected youth, using generalized estimating equation models adjusting for other covariates. The prevalence and time to incident hypercholesterolemia were also compared between these 2 groups. RESULTS: After adjustment for confounders, 52 youth with prescriptions for SGAs had a larger increase in TC levels than 148 matched youth without antipsychotic prescriptions (mean difference = 9 mg/dL, z = 1.96, df = 1, P = 0.0496). Among youth with TC below 220 mg/dL at baseline, 27% of SGA-exposed youth developed hypercholesterolemia (defined as two consecutive TC measurements ≥220 mg/dL), compared with 13% of SGA-unexposed patients (Fisher's exact test, P = 0.046). CONCLUSIONS: Caution should be used in prescribing SGAs to perinatally HIV-infected youth with psychiatric co-morbidities due to increased risk of hypercholesterolemia. Patients should be monitored, and alternative evidence-based treatments considered when available.

8.
AIDS Patient Care STDS ; 23(11): 939-47, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19827949

RESUMO

Second-generation antipsychotics (SGAs) are increasingly prescribed to treat psychiatric symptoms in pediatric patients infected with HIV. We examined the relationship between prescribed SGAs and physical growth in a cohort of youth with perinatally acquired HIV-1 infection. Pediatric AIDS Clinical Trials Group (PACTG), Protocol 219C (P219C), a multicenter, longitudinal observational study of children and adolescents perinatally exposed to HIV, was conducted from September 2000 until May 2007. The analysis included P219C participants who were perinatally HIV-infected, 3-18 years old, prescribed first SGA for at least 1 month, and had available baseline data prior to starting first SGA. Each participant prescribed an SGA was matched (based on gender, age, Tanner stage, baseline body mass index [BMI] z score) with 1-3 controls without antipsychotic prescriptions. The main outcomes were short-term (approximately 6 months) and long-term (approximately 2 years) changes in BMI z scores from baseline. There were 236 participants in the short-term and 198 in the long-term analysis. In linear regression models, youth with SGA prescriptions had increased BMI z scores relative to youth without antipsychotic prescriptions, for all SGAs (short-term increase = 0.192, p = 0.003; long-term increase = 0.350, p < 0.001), and for risperidone alone (short-term = 0.239, p = 0.002; long-term = 0.360, p = 0.001). Participants receiving both protease inhibitors (PIs) and SGAs showed especially large increases. These findings suggest that growth should be carefully monitored in youth with perinatally acquired HIV who are prescribed SGAs. Future research should investigate the interaction between PIs and SGAs in children and adolescents with perinatally acquired HIV infection.


Assuntos
Antipsicóticos , Índice de Massa Corporal , Infecções por HIV/complicações , Transmissão Vertical de Doença Infecciosa , Transtornos Mentais/tratamento farmacológico , Adolescente , Desenvolvimento do Adolescente/efeitos dos fármacos , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Estudos de Casos e Controles , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Infecções por HIV/virologia , HIV-1 , Humanos , Estudos Longitudinais , Resultado do Tratamento
9.
Am J Prev Med ; 37(2): 150-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19524394

RESUMO

BACKGROUND: Despite the acknowledged promise of developing a public health systems research (PHSR) agenda for emergency preparedness, there has been no systematic review of the literature in this area. The purpose of this study was to conduct a systematic literature review in order to identify and characterize the PHSR literature produced in the U.S. in the past 11 years in the field of public health emergency preparedness. EVIDENCE ACQUISITION: Articles were searched in MEDLINE and EMBASE, as well as in the gray literature. Two independent reviewers classified the articles according to study design and IOM public health emergency preparedness (PHEP) research goal areas. EVIDENCE SYNTHESIS: From January 1, 1997, through December 31, 2008, there were 547 articles that met the inclusion criteria that were published. It was possible to classify 314 (57%) articles into at least one of the four IOM PHEP research goal areas. Of these, 61 (11%) addressed Research Area 1 (usefulness of training); 39 (7%) addressed Research Area 2 (communications in preparedness and response); 193 (35%) addressed Research Area 3 (sustainable preparedness and response systems); and 39 (7%) addressed Research Area 4 (criteria and metrics to measure effectiveness and efficiency). Twenty-one studies (4%) could be classified into more than one category. The majority of the articles (81%), including commentaries/reviews and case studies, were based on qualitative analysis. Commentaries/review articles were the most common study types (62%). CONCLUSIONS: Since 2001, the PHSR literature on PHEP issues has grown at about 33% per year. However, most studies lack a rigorous design, raising questions about the validity of the results.


Assuntos
Planejamento em Desastres/organização & administração , Pesquisa sobre Serviços de Saúde/métodos , Projetos de Pesquisa/normas , Serviços Médicos de Emergência/organização & administração , Humanos , Saúde Pública/métodos , Estados Unidos
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