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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.
PLoS Med ; 16(9): e1002907, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31509529

RESUMO

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

3.
Clin Infect Dis ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31414121

RESUMO

Although it is common to analyze efficacy and safety separately in clinical trials, this approach could yield a misleading study conclusion if an increase in efficacy is accompanied by a decrease in safety. Risk-benefit analysis is a systematic approach to examine safety and efficacy jointly. Both "rank-based" and "partial-credit" methods described in this paper allow researchers to create a single composite outcome incorporating efficacy, safety, and other factors. The first approach compares the distribution of rankings between arms. In the second approach, a score can be assigned to each outcome category considering its severity and the mean or median scores of arms are compared. The methods were applied to the A5279/BRIEF-TB study and design considerations for future clinical trials are discussed, including the challenge of arriving at a consensus on rankings/scorings. If well-designed, risk-benefit analysis may allow researchers to conduct a superiority comparison and therefore avoid setting a non-inferiority margin. CLINICALTRIAL.GOV IDENTIFIER: NCT01404312 (A5279).

4.
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
5.
PLoS One ; 11(2): e0148649, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26872154

RESUMO

BACKGROUND: This study examined the associations of 25-hydroxyvitamin D and specific host genetic variants that affect vitamin D levels or its effects on immune function, with the risk of TB or mortality in children. METHODS: A case-cohort sample of 466 South African infants enrolled in P1041 trial (NCT00080119) underwent 25-hydroxyvitamin D testing by chemiluminescent immunoassay. Single nucleotide polymorphisms (SNPs) that alter the effect of vitamin D [e.g. vitamin D receptor (VDR)], vitamin D levels [e.g. vitamin D binding protein (VDBP)], or toll like receptor (TLR) expression (SIGIRR including adjacent genes PKP3 and TMEM16J) were identified by real-time PCR. Outcomes were time to TB, and to the composite of TB or death by 192 weeks of follow-up. Effect modification between vitamin D status and SNPs for outcomes was assessed. FINDINGS: Median age at 25-hydroxyvitamin D determination was 8 months; 11% were breastfed, 51% were HIV-infected and 26% had low 25-hydroxyvitamin D (<32ng/mL). By 192 weeks, 138 incident TB cases (43 definite/probable, and 95 possible) and 26 deaths occurred. Adjusting for HIV status and potential confounders, low 25-hydroxyvitamin D was associated with any TB (adjusted hazard ratio [aHR] 1.76, 95% CI 1.01-3.05; p = 0.046) and any TB or death (aHR 1.76, 95% CI 1.03-3.00; p = 0.038). Children with low 25-hydroxyvitamin D and TMEM 16J rs7111432-AA or PKP3 rs10902158-GG were at increased risk for probable/definite TB or death (aHR 8.12 and 4.83, p<0.05) and any TB or death (aHR 4.78 and 3.26, p<0.005) respectively; SNPs in VDBP, VDR, and vitamin D precursor or hydroxylation genes were not. There was significant interaction between low 25-hydroxyvitamin D and, TMEM 16J rs7111432-AA (p = 0.04) and PKP3 rs10902158-GG (p = 0.02) SNPs. CONCLUSIONS: Two novel SNPs, thought to be associated with innate immunity, in combination with low vitamin D levels were identified as increasing a young child's risk of developing TB disease or death. Identifying high-risk children and providing targeted interventions such as vitamin D supplementation may be beneficial. TRIAL REGISTRATION: ClinicalTrials.gov NCT00080119.


Assuntos
Infecções por HIV/genética , Proteínas de Membrana/genética , Placofilinas/genética , Tuberculose Pulmonar/genética , Deficiência de Vitamina D/genética , Vitamina D/análogos & derivados , Adulto , Anoctaminas , Estudos de Coortes , Feminino , Seguimentos , Expressão Gênica , Predisposição Genética para Doença , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Humanos , Lactente , Masculino , Proteínas de Membrana/imunologia , Proteínas de Transferência de Fosfolipídeos , Placofilinas/imunologia , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Calcitriol/genética , Receptores de Calcitriol/imunologia , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/imunologia , Análise de Sobrevida , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/mortalidade , Vitamina D/sangue , Vitamina D/imunologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/mortalidade , Proteína de Ligação a Vitamina D/genética , Proteína de Ligação a Vitamina D/imunologia
6.
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
7.
Clin Infect Dis ; 62(6): 761-769, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26658057

RESUMO

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population.


Assuntos
Antituberculosos/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Tuberculose Latente/tratamento farmacológico , Período Pós-Parto , Tuberculose Resistente a Múltiplos Medicamentos/prevenção & controle , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controle , Adulto , Antituberculosos/farmacocinética , Ensaios Clínicos como Assunto/ética , Ensaios Clínicos como Assunto/legislação & jurisprudência , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose Latente/sangue , Tuberculose Latente/microbiologia , Gravidez , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Estados Unidos
9.
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
10.
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
11.
J Infect Dis ; 205 Suppl 2: S209-15, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22476719

RESUMO

Confirming the diagnosis of childhood tuberculosis is a major challenge. However, research on childhood tuberculosis as it relates to better diagnostics is often neglected because of technical difficulties, such as the slow growth in culture, the difficulty of obtaining specimens, and the diverse and relatively nonspecific clinical presentation of tuberculosis in this age group. Researchers often use individually designed criteria for enrollment, diagnostic classifications, and reference standards, thereby hindering the interpretation and comparability of their findings. The development of standardized research approaches and definitions is therefore needed to strengthen the evaluation of new diagnostics for detection and confirmation of tuberculosis in children. In this article we present consensus statements on methodological issues for conducting research of Tuberculosis diagnostics among children, with a focus on intrathoracic tuberculosis. The statements are complementary to a clinical research case definition presented in an accompanying publication and suggest a phased approach to diagnostics evaluation; entry criteria for enrollment; methods for classification of disease certainty, including the rational use of culture within the case definition; age categories and comorbidities for reporting results; and the need to use standard operating procedures. Special consideration is given to the performance of microbiological culture in children and we also recommend for alternative methodological approaches to report findings in a standardized manner to overcome these limitations are made. This consensus statement is an important step toward ensuring greater rigor and comparability of pediatric tuberculosis diagnostic research, with the aim of realizing the full potential of better tests for children.


Assuntos
Projetos de Pesquisa , Tuberculose Pulmonar/diagnóstico , Adolescente , Antituberculosos/uso terapêutico , Técnicas Bacteriológicas/tendências , Criança , Pré-Escolar , Humanos , Lactente , Padrões de Referência , Tuberculose Pulmonar/tratamento farmacológico
12.
Pediatrics ; 129(5): e1244-51, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22508915

RESUMO

OBJECTIVE: Nonadherence to antiretroviral therapy among children/youth with HIV often is associated with disease progression. This study examined the agreement between child and caregiver perceptions of barriers to adherence and factors associated with these barriers. METHODS: Children/youth with perinatally acquired HIV and their parents/caregivers (n = 120 dyads) completed a questionnaire about 19 potential barriers to adherence to the child's antiretroviral therapy regimen. Agreement between the 2 reports was measured via the kappa statistic. Factors associated with the barriers were assessed by using multiple logistic regression. RESULTS: Of the 120 children, 55% were African American, 54% were boys, and the average age was 12.8 years. The most frequently reported barrier by either the caregiver or youth was "forgot." There were varying degrees of agreement between child and caregiver on the following barriers: "forgot," "taste," "child was away from home," "child refused," and "child felt good." Children who knew their HIV status were more likely to report logistical barriers, such as scheduling issues. Children with a biological parent as their caregiver were more likely to report regimen or fear of disclosure as a barrier. CONCLUSIONS: Lack of agreement was observed for more than half of the studied barriers, indicating discrepancies between children's and caregivers' perceptions of factors that influence medication-taking. The findings suggest a need for interventions that involve both child and caregiver in the tasks of remembering when to administer the child's medications, sustaining adherence, and appropriately transitioning medication responsibility to the youth.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Cuidadores/educação , Cuidadores/psicologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Inibidores da Protease de HIV/administração & dosagem , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação/psicologia , Pais/psicologia , Adolescente , Criança , Feminino , Infecções por HIV/congênito , Inibidores da Protease de HIV/efeitos adversos , Humanos , Estudos Longitudinais , Masculino , Pais/educação , Educação de Pacientes como Assunto , Fatores de Risco , Autocuidado/psicologia , Responsabilidade Social , Estatística como Assunto , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
13.
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
14.
J Dev Behav Pediatr ; 33(4): 298-308, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22366661

RESUMO

OBJECTIVE: Medication adherence is critical to the success of antiretroviral therapies for children and youth with perinatally acquired HIV. Factors that influence successful transition of medication responsibility from caregivers to youth are poorly understood. The purpose of this study was to evaluate the relationship of medication adherence with demographic, cognitive, academic, and behavioral characteristics. METHODS: Randomly selected youth, N = 151, aged 8 to 18 years, completed cognitive and academic measures, and they and their caregivers completed questionnaires assessing behavior and emotional well-being. An announced pill count and questionnaires completed by youth and their caregivers were used to evaluate adherence. RESULTS: Of 151 participants, 100 completed all adherence measures. Adherence rates varied by assessment method. Nonadherence (<90%) by pill count was associated with older child age, greater youth responsibility for medications, and other demographic and medication regimen variables. Verbal impairment predicted better self-reported adherence and reading problems predicted better self- and caregiver-reported adherence. Youth-reported locus of control was associated with pill count nonadherence, and poor relationships with parents were associated with youth-reported nonadherence. CONCLUSIONS: Consideration of youth cognitive or academic status may be helpful in evaluating medication adherence in patients with perinatally acquired HIV infection, particularly when using self- or caregiver reports to assess adherence. Vigilance for adherence problems is indicated when youth are older, responsible for medications, report poor caregiver relationships, and/or sense a lack of control over their lives.


Assuntos
Comportamento do Adolescente/psicologia , Comportamento Infantil/psicologia , Infecções por HIV/psicologia , Adesão à Medicação/psicologia , Adolescente , Fatores Etários , Antirretrovirais/administração & dosagem , Criança , Ensaios Clínicos como Assunto , Estudos Transversais , Esquema de Medicação , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/etiologia , Humanos , Controle Interno-Externo , Masculino , Testes Neuropsicológicos , Escalas de Wechsler
15.
AIDS Patient Care STDS ; 25(3): 191-200, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21323533

RESUMO

The impact of behavioral functioning on medication adherence in children with perinatally acquired HIV infection is not well-explored, but has important implications for intervention. This report addresses the relationship between behavioral functioning and child self-report or caregiver report of medication adherence among children and adolescents enrolled in Pediatric AIDS Clinical Trials Group Protocol 219C (conducted 2000-2007). A total of 1134 participants, aged 3-17 years, received a behavioral evaluation and adherence assessment. Complete adherence was defined as taking 100% of prescribed antiretroviral medications during three days preceding the study visit. Multivariable logistic regression models were used to evaluate associations between adherence and behavioral functioning, adjusting for potential confounders, including demographic, psychosocial, and health factors. Children demonstrated higher than expected rates of behavioral impairment (≈7% expected with T > 65) in the areas of conduct problems (14%, z = 7.0, p < 0.001), learning problems (22%, z = 12.2, p < 0.001), somatic complaints (22%, z = 12.6, p < 0.001), impulsivity-hyperactivity (20%, z = 11.1, p < 0.001), and hyperactivity (19%, z = 10.6, p < 0.001). Children with behavioral impairment in one or more areas had significantly increased odds of nonadherence [adjusted odds ratio (aOR) = 1.49, p = 0.04]. The odds of nonadherence were significantly higher for those with conduct problems and general hyperactivity (aOR = 2.03, p = 0.005 and aOR = 1.68, p = 0.02, respectively). Psychosocial and health factors, such as recent stressful life events and higher HIV RNA levels, were also associated with nonadherence. Knowledge of behavioral, health, and social influences affecting the child and family should guide the development of appropriate, evidence-based interventions for medication adherence.


Assuntos
Comportamento do Adolescente , Fármacos Anti-HIV/uso terapêutico , Transtornos do Comportamento Infantil , Infecções por HIV/tratamento farmacológico , Cooperação do Paciente/psicologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino
16.
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.

17.
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
18.
J Dev Behav Pediatr ; 30(5): 403-12, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19827220

RESUMO

OBJECTIVE: To examine the relationships between physical growth and medications prescribed for symptoms of attention-deficit hyperactivity disorder in children with HIV. METHODS: Analysis of data from children with perinatally acquired HIV (N = 2251; age 3-19 years), with and without prescriptions for stimulant and nonstimulant medications used to treat attention-deficit hyperactivity disorder, in a long-term observational study. Height and weight measurements were transformed to z scores and compared across medication groups. Changes in z scores during a 2-year interval were compared using multiple linear regression models adjusting for selected covariates. RESULTS: Participants with (n = 215) and without (n = 2036) prescriptions were shorter than expected based on US age and gender norms (p < .001). Children without prescriptions weighed less at baseline than children in the general population (p < .001) but gained height and weight at a faster rate (p < .001). Children prescribed stimulants were similar to population norms in baseline weight; their height and weight growth velocities were comparable with the general population and children without prescriptions (for weight, p = .511 and .100, respectively). Children prescribed nonstimulants had the lowest baseline height but were similar to population norms in baseline weight. Their height and weight growth velocities were comparable with the general population but significantly slower than children without prescriptions (p = .01 and .02, respectively). CONCLUSION: The use of stimulants to treat symptoms of attention-deficit hyperactivity disorder does not significantly exacerbate the potential for growth delay in children with HIV and may afford opportunities for interventions that promote physical growth. Prospective studies are needed to confirm these findings.


Assuntos
Desenvolvimento do Adolescente/efeitos dos fármacos , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Desenvolvimento Infantil/efeitos dos fármacos , Infecções por HIV/complicações , Adolescente , Análise de Variância , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Adulto Jovem
19.
J Pediatr Psychol ; 34(2): 164-75, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18647794

RESUMO

OBJECTIVE: To evaluate the relationship between cognitive functioning and medication adherence in children and adolescents with perinatally acquired HIV infection. METHODS: Children and adolescents, ages 3-18 (N = 1,429), received a cognitive evaluation and adherence assessment. Multiple logistic regression models were used to identify associations between adherence and cognitive status, adjusting for potential confounding factors. RESULTS: Children's average cognitive performance was within the low-average range; 16% of children were cognitively impaired (MDI/FSIQ <70). Cognitive status was not associated with adherence to full medication regimens; however, children with borderline/low average cognitive functioning (IQ 70-84) had increased odds of nonadherence to the protease inhibitor class of antiretroviral therapy. Recent stressful life events and child health characteristics, such as HIV RNA detectability, were significantly associated with nonadherence. CONCLUSION: Cognitive status plays a limited role in medication adherence. Child and caregiver psychosocial and health characteristics should inform interventions to support adherence.


Assuntos
Antirretrovirais/uso terapêutico , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Cooperação do Paciente/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Testes de Inteligência , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Índice de Gravidade de Doença
20.
J Pediatr Psychol ; 34(2): 187-94, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18586756

RESUMO

OBJECTIVE: The purpose of the study is to describe allocation of responsibility for illness management in families of children and adolescents perinatally infected with HIV. METHODS: A total of 123 youth (ages 8-18) and caregivers completed family responsibility and medication adherence questionnaires as part of a substudy of Pediatric AIDS Clinical Trials Group protocol 219c. RESULTS: Approximately one-fourth of the youth reported being fully responsible for taking medications. A smaller percentage of caregivers reported full youth responsibility. Older youth and caregivers of older youth reported higher degree of youth responsibility for medication-related tasks, though age was unrelated to adherence. Caregiver report of greater responsibility for medications was associated with better adherence. CONCLUSIONS: Caregivers are likely to transition responsibility for HIV care to older youth but this transition was not always successful as evidenced by poor medication adherence. Interventions supporting successful transition may improve adherence and subsequently health outcomes in pediatric HIV.


Assuntos
Efeitos Psicossociais da Doença , Família/psicologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Cooperação do Paciente/estatística & dados numéricos , Inibidores de Proteases/uso terapêutico , Responsabilidade Social , Adolescente , Criança , Feminino , Humanos , Masculino , Inquéritos e Questionários , Adulto Jovem
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