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1.
PLoS One ; 14(12): e0226375, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856189

RESUMO

To assess and compare the prevalence of persistent hepatic abnormalities, including nonalcoholic fatty liver disease (NAFLD) and/or hepatic fibrosis, among perinatally HIV-monoinfected Asian adolescents with history of abnormal hepatic enzymes to those without, using noninvasive diagnostic tools. A multicenter cohort study was conducted in Thailand and Indonesia. Adolescents aged 10-25 years who were on antiretroviral treatment (ART), had virologic suppression (HIV RNA<400 copies/mL within the past 6 months), and had no history of chronic hepatitis B/C infection were enrolled. Participants were pre-classified into 2 subgroups (1:1 ratio) as participants with history of elevated versus normal aminotransferase enzymes. NAFLD was defined as hepatic steatosis (any severity) evaluated by liver ultrasonography. Significant hepatic fibrosis was defined as liver stiffness ≥7.4 kPa evaluated by transient elastography. Participants who met the criteria for protocol-defined NAFLD and/or hepatic fibrosis were re-assessed to evaluate disease progression (persistent versus transient hepatic abnormalities) at one year later. Of 120 participants, 62 (51.7%) were male, 7 (5.8%) had central obesity, and 19 (15.8%) had insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] >3.16). At enrollment, the median age and duration of ART (IQR) were 17.0 (14.6-19.2) years and 10.5 (7.1-12.0) years, respectively. Persistent hepatic abnormalities were identified in 5/60 participants listed in the group having history of elevated aminotransferases, corresponding to the prevalence of 8.3% (95% CI: 2.8-18.4%), whereas none (0/60) were among the group having history of normal hepatic enzymes. All 5 participants had persistent aminotransferase elevation (≥2 episodes within the past 12 months). Baseline alanine aminotransferase (ALT) >30 U/L (adjusted odds ratio [aOR]: 29.1; 95% CI: 1.7-511.8), and HOMA-IR >3.16 (aOR: 17.9; 95% CI: 1.1-289.7) were independently associated with persistent hepatic abnormalities. Among perinatally HIV-monoinfected Asian adolescents with history of elevated aminotransferase enzymes, persistent hepatic abnormalities are not uncommon. Screening for liver complications by noninvasive diagnostic tools might be considered in at risk individuals, including those with persistent ALT elevation and insulin resistance.

2.
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
3.
AIDS ; 33 Suppl 1: S17-S27, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31397719

RESUMO

OBJECTIVES: Psychosocial challenges associated with perinatally acquired HIV (PHIV) infection are well known, yet many children infected with HIV since birth demonstrate positive outcomes, referred to as resilience. The purpose of this study was to evaluate emotional-behavioral development and identify salient predictors of resilience among long-term survivors of PHIV. DESIGN: Prospective investigation of children with PHIV compared with demographically similar perinatally HIV-exposed but uninfected (PHEU) and HIV-unexposed, uninfected (HUU) children, all from Thailand and Cambodia. METHODS: The Child Behavior Checklist (CBCL; parent version) was administered at baseline and annual follow-up visits (median follow-up of 3 years) to children age 6-14. Resilience was defined as consistent CBCL scores on the Internalizing, Externalizing or Total Problem T scales within normative ranges (T-scores <60) at every time point. Generalized estimating equations examined CBCL scores over time and logistic models examined demographic, socioeconomic, and cultural predictors of resilience. RESULTS: Participants included 448 children (236 PHIV, 98 PHEU, 114 HUU), with median (interquartile range) age at first evaluation of 7 (6-9) years. Children with PHIV exhibited similar rates of resilience as PHEU and HUU on the Externalizing and Total Problems scales. Resilience on the Internalizing scale was more likely in PHEU (71%) compared with PHIV (59%) or HUU (56%), P = 0.049. Factors associated with resilience in adjusted models included: HIV-exposed but uninfected status, higher household income, Cambodian nationality, female sex, and caregiver type. CONCLUSION: Despite biopsychosocial risks, resilience is observed among PHIV and PHEU children. Further study is needed to understand mechanisms underlying associated factors and intervention priorities.

4.
AIDS Res Hum Retroviruses ; 35(11-12): 1136-1142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31382762

RESUMO

Cardiovascular disease (CVD) is one among the leading causes of mortality in people living with HIV on antiretroviral treatment (ART) worldwide. We examined the prevalence of subclinical atherosclerosis, associated factors, and risk of CVD in older adults living with HIV (OALHIV). A cross-sectional study was conducted with patients aged ≥50 years with HIV infection receiving ART at community hospitals in Chiang Mai, Thailand. Age- and sex-matched patients without documented HIV infection who visited the general outpatient department were enrolled for comparison. Cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) were measured using the vascular screening system, VaSera System™ (Fukuda Denshi Co., Ltd., Japan) to determine subclinical atherosclerosis (defined as CAVI ≥9.0) and peripheral arterial disease (defined as ABI <0.9), respectively. The Ramathibodi-Electric Generating Authority of Thailand (RAMA-EGAT) scores to predict the risk of coronary stenosis and the 10-year risk of ASCVD by pooled cohort equation were calculated. One hundred fifty-five patients were enrolled (107 HIV/48 comparison). The mean age was 59.0 years (SD 6.1); 67 (43%) were male. Participants in the HIV and comparison group were similar with respect to abnormal CAVI (57% vs. 58%, p = .88), abnormal ABI (6% vs. 8%, p = .50), and the risk of coronary stenosis (34% vs. 44%, p = .23). However, the 10-year risk of ASCVD was lower in HIV than in the comparison group (29% vs. 48%, p = .02). In OALHIV, diabetes mellitus was the only factor associated with abnormal CAVI. The cardiovascular risk among OALHIV in this study was similar to non-HIV population. More than a half of them had abnormal CAVI, and approximately one-third was at ≥10% 10-year risk of ASCVD.

5.
J Acquir Immune Defic Syndr ; 82(3): 297-304, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31335589

RESUMO

BACKGROUND: Large numbers of perinatally HIV-infected (PHIV) children are aging into adolescence. We examined cognitive and behavioral outcomes in a longitudinal cohort of Asian youth. METHODS: We followed up 231 PHIV, 125 perinatally HIV-exposed, uninfected (HEU), and 138 HIV-unexposed, uninfected (HUU) adolescents (aged 10 years and older), matched by age/sex, in Thailand and Cambodia for 3 years. Executive function was assessed with Children's Color Trails Tests 1 and 2 (CCTT-1 and -2), the design fluency test, and the verbal fluency test. Working memory (Freedom from Distractibility Index) and processing speed index were assessed using WISC-III. Visual memory was assessed by design memory and design recognition subtests of the Wide Range Assessment of Memory and Learning (WRAML-2) and behavioral problems using the Child Behavior Checklist (CBCL). Generalized estimating equations examined adjusted odds ratios of cognitive impairment (Z-scores ≥2 SD below age-adjusted means of the HUU group) and CBCL T-scores in the borderline-clinical range (T-Scores ≥60) in PHIV and HEU versus HUU youth, adjusting for ethnicity, household income, and caregiver characteristics. RESULTS: The median age at enrollment was 13.8 years, with 58% women and 63% Thai participants. PHIV youth had >86% virological suppression and significantly higher impairment rates on CCTT-1 and -2 tests, design fluency test, verbal fluency tests, design memory, and CBCL internalizing and externalizing problems. Results were mostly similar between HEU and HUU groups, apart from higher impairment rates on CCTT-1 and internalizing problems in HEU. CONCLUSION: Asian adolescents with PHIV remain at risk of cognitive and mental health problems despite HIV treatment. Selective risks are observed among HEU youth.

6.
PLoS One ; 14(5): e0216382, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31048890

RESUMO

BACKGROUND: Disclosure of HIV status is a critical gateway to HIV prevention. Despite many studies on this topic, there is a gap in knowledge regarding HIV status disclosure and risky sexual behavior in HIV-infected female migrant workers. The current study addressed this research gap, and focused on HIV-infected Shan female migrant workers in Northern Thailand. METHODS: This study conducted in-depth interviews with 18 HIV-infected Shan female migrants (aged between 23-54 years old) and 29 healthcare workers in district hospitals in Chiang Mai. Content analysis was employed to identify particular themes related to HIV status disclosure, sexual risk behavior, and ART adherence. RESULTS: We found that non-disclosure to husbands/partners was mostly related to fear of marital conflict and of losing social and financial support. Non-disclosure prevented Shan female migrant workers from negotiating condom use with their partners. Reasons for not disclosing to friends, family and other community members were mostly related to feared rejection and discrimination due to HIV-related stigma. Accounts of condomless sex in the context of HIV status disclosure suggest that gender norms and male dominance over women influenced decision-making for safe sex. Lastly, some female migrant workers perceived low risk of HIV transmission with good adherence to the ART. CONCLUSIONS: This study highlighted the complex challenges of HIV status disclosure among HIV-positive Shan female migrant workers and the link between disclosure/non-disclosure and condom use. There is a pressing need to create realistic disclosure mechanisms that take into account the socio-cultural barriers to disclosure including marital conflicts, stigma, and gender norms. Messages to encourage condom use should be delivered carefully so that knowledge of the HIV transmission reduction qualities of good ART adherence does not serve as a barrier to condom use.


Assuntos
Infecções por HIV/etnologia , Infecções por HIV/epidemiologia , Comportamentos de Risco à Saúde , Comportamento Sexual , Estigma Social , Migrantes , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Tailândia
7.
Neuroimage Clin ; 23: 101810, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31029050

RESUMO

Alterations in subcortical brain structures have been reported in adults with HIV and, to a lesser extent, pediatric cohorts. The extent of longitudinal structural abnormalities in children with perinatal HIV infection (PaHIV) remains unclear. We modeled subcortical morphometry from whole brain structural magnetic resonance imaging (1.5 T) scans of 43 Thai children with PaHIV (baseline age = 11.09±2.36 years) and 50 HIV- children (11.26±2.80 years) using volumetric and surface-based shape analyses. The PaHIV sample were randomized to initiate combination antiretroviral treatment (cART) when CD4 counts were 15-24% (immediate: n = 22) or when CD4 < 15% (deferred: n = 21). Follow-up scans were acquired approximately 52 weeks after baseline. Volumetric and shape descriptors capturing local thickness and surface area dilation were defined for the bilateral accumbens, amygdala, putamen, pallidum, thalamus, caudate, and hippocampus. Regression models adjusting for clinical and demographic variables examined between and within group differences in morphometry associated with HIV. We assessed whether baseline CD4 count and cART status or timing associated with brain maturation within the PaHIV group. All models were adjusted for multiple comparisons using the false discovery rate. A pallidal subregion was significantly thinner in children with PaHIV. Regional thickness, surface area, and volume of the pallidum was associated with CD4 count in children with PaHIV. Longitudinal morphometry was not associated with HIV or cART status or timing, however, the trajectory of the left pallidum volume was positively associated with baseline CD4 count. Our findings corroborate reports in adult cohorts demonstrating a high predilection for HIV-mediated abnormalities in the basal ganglia, but suggest the effect of stable PaHIV infection on morphological aspects of brain development may be subtle.

8.
J Int Assoc Provid AIDS Care ; 18: 2325958218823259, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798669

RESUMO

BACKGROUND: Hepatitis B virus (HBV) and HIV coinfection is associated with risk of progression to chronic liver disease. We assessed liver stiffness in HBV-HIV coinfected youths. METHODS: A cross-sectional study in HBV-HIV coinfected youths aged 18 to 25 years who received a tenofovir (TDF)-containing antiretroviral therapy regimen for >96 weeks. Measurements included HBV DNA level, HBV serology profiles, and transient elastography (TE). The cutoff for TE results included ≥5.9 kPa for F2-moderate fibrosis, ≥7.4 kPa for F3-severe fibrosis, and ≥9.6 kPa for F4-cirrhosis. RESULTS: From March to December 2016, 15 HBV-HIV coinfected youths with a median duration on TDF-containing regimens of 3.3 years were enrolled. Five (33%) youths had significant liver fibrosis, 3 with F2-moderate, 1 with F3-advanced fibrosis, and 1 with F4-cirrhosis. Other 5 without liver fibrosis had hepatitis B surface e antigen (HBsAg) and hepatitis B surface e antigen (HBeAg) loss. Higher mean alanine transaminase (ALT) was observed among the group with F2-F4 when compared to those with F0. CONCLUSION: Liver fibrosis was evidenced in HBV-HIV coinfected youths in Thailand. Transient elastography might be considered for those who do not achieve HBsAg loss or have persistent ALT elevation while on treatment.

9.
Clin Infect Dis ; 68(2): 273-279, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-29868833

RESUMO

Background: Adverse pregnancy outcomes for women who conceive on antiretroviral therapy (ART) may be increased, but data are conflicting. Methods: Human immunodeficiency virus-infected, nonbreastfeeding women with pre-ART CD4 counts ≥400 cells/µL who started ART during pregnancy were randomized after delivery to continue ART (CTART) or discontinue ART (DCART). Women randomized to DCART were recommended to restart if a subsequent pregnancy occurred or for clinical indications. Using both intent-to-treat and as-treated approaches, we performed Fisher exact tests to compare subsequent pregnancy outcomes by randomized arm. Results: Subsequent pregnancies occurred in 277 of 1652 (17%) women (CTART: 144/827; DCART: 133/825). A pregnancy outcome was recorded for 266 (96%) women with a median age of 27 years (interquartile range [IQR], 24-31 years) and median CD4+ T-cell count 638 cells/µL (IQR, 492-833 cells/µL). When spontaneous abortions and stillbirths were combined, there was a significant difference in events, with 33 of 140 (23.6%) in the CTART arm and 15 of 126 (11.9%) in the DCART arm (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.1-3.5]; P = .02). In the as-treated analysis, the RR was reduced and no longer statistically significant (RR, 1.4 [95% CI, .8-2.4]). Conclusions: Women randomized to continue ART who subsequently conceived were more likely to have spontaneous abortion or stillbirth, compared with women randomized to stop ART; however, the findings did not remain significant in the as-treated analysis. More data are needed on pregnancy outcomes among women conceiving on ART, particularly with newer regimens.


Assuntos
Aborto Espontâneo/induzido quimicamente , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Natimorto , Adulto , Antirretrovirais/administração & dosagem , Feminino , Humanos , Gravidez , Adulto Jovem
10.
AIDS ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31895148

RESUMO

OBJECTIVE: To develop a predictive model of neurocognitive trajectories in children with perinatal HIV (pHIV). DESIGN: Machine learning analysis of baseline and longitudinal predictors derived from clinical measures utilized in pediatric HIV. METHODS: 285 children (ages 2-14 years at baseline; Mage = 6.4 years) with pHIV in Southeast Asia underwent neurocognitive assessment at study enrollment and twice annually thereafter for an average of 5.4 years. Neurocognitive slopes were modeled to establish two subgroups (above (n = 145) and below average (n = 140) trajectories). Gradient-boosted multivariate regressions (GBM) with five-fold cross validation were conducted to examine baseline (pre-ART) and longitudinal predictive features derived from demographic, HIV disease, immune, mental health, and physical health indices (i.e., complete blood count; CBC). RESULTS: The baseline GBM established a classifier of neurocognitive group designation with an average AUC of 79% built from HIV disease severity and immune markers. GBM analysis of longitudinal predictors with and without interactions improved the average AUC to 87% and 90%, respectively. Mental health problems and hematocrit levels also emerged as salient features in the longitudinal models, with novel interactions observed between mental health problems and both CD4 count and hematocrit levels. Average AUCs derived from each GBM model were higher than results obtained using logistic regression. CONCLUSIONS: Our findings support the feasibility of machine learning to identify children with pHIV at risk for suboptimal neurocognitive development. Results also point towards interactions between HIV disease and mental health problems as early antecedents to neurocognitive difficulties in later childhood among individuals with pHIV.

11.
J Int Assoc Provid AIDS Care ; 17: 2325958218774782, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29756549

RESUMO

This study aimed to assess family functioning in adolescents with perinatal HIV infection receiving antiretroviral therapy compared with healthy controls. Correlations between self-reported and caregiver-reported family functions were also evaluated. A sample of 195 participants including 65 perinatally HIV-infected adolescents and 130 healthy controls were enrolled. The total family functioning score in HIV-infected adolescents was significantly lower than that in healthy controls by self-report (105.86 vs 115.41; P ≤ .001). Caregivers of HIV-infected adolescents also reported lower scores of family functioning than those of controls (109.91 vs 114.98; P ≤ .001). Among the HIV-infected group, there was no or minimal correlation between the self-reported and caregiver-reported total scores of family functioning. However, there were moderate correlations between self-reported and caregiver-reported family functioning total scores in the control group. Overall, HIV-infected adolescents reported lower family functioning than healthy controls. Improved functioning in the family may help with better adjustment in perinatally HIV-infected adolescents.


Assuntos
Terapia Antirretroviral de Alta Atividade , Cuidadores , Relações Familiares , Infecções por HIV/tratamento farmacológico , Adolescente , Fatores Etários , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Transmissão Vertical de Doença Infecciosa , Masculino , Adesão à Medicação , Assistência Perinatal , Inquéritos e Questionários , Tailândia
12.
Pediatr Infect Dis J ; 37(8): 788-793, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29846357

RESUMO

BACKGROUND: Hepatitis B (HBV)-HIV coinfection is associated with liver inflammation, which can progress to liver fibrosis/cirrhosis and hepatocellular carcinoma. We determined HBV seroprevalence in children and adolescents participating in the TREAT Asia Pediatric HIV Observational Database. METHODS: A multisite cross-sectional study was conducted in HIV-infected patients currently <25 years old receiving antiretroviral treatment (ART) who had HBV surface antigen (HBsAg), or HBV surface antibody (anti-HBs) or HBV core antibody (anti-HBc) tested during 2012-2013. HBV coinfection was defined as having either a positive HBsAg test or being anti-HBc positive and anti-HBs negative, reflective of past HBV infection. HBV seroprotection was defined as having a positive anti-HBs test. RESULTS: A total of 3380 patients from 6 countries (Vietnam, Thailand, Cambodia, Malaysia, Indonesia and India) were included. The current median (interquartile range) age was 11.2 (7.8-15.1) years. Of the 2755 patients (81.5%) with HBsAg testing, 130 (4.7%) were positive. Of 1558 (46%) with anti-HBc testing, 77 (4.9%) were positive. Thirteen of 1037 patients with all 3 tests were anti-HBc positive and HBsAg and anti-HBs negative. One child was positive for anti-HBc and negative for anti-HBs but did not have HBsAg tested. The prevalence of HBV coinfection was 144/2759 (5.2%) (95% confidence interval: 4.4-6.1). Of 1093 patients (32%) with anti-HBs testing, 257 (23.5%; confidence interval: 21.0-26.0) had positive tests representing HBV seroprotection. CONCLUSIONS: The estimated prevalence of HBV coinfection in this cohort of Asian HIV-infected children and adolescents on ART was 5.2%. The majority of children and adolescents tested in this cohort (76.5%) did not have protective HBV antibody. The finding supports HBV screening of HIV-infected children and adolescents to guide revaccination, the use of ART with anti-HBV activity and future monitoring.


Assuntos
Antirretrovirais/uso terapêutico , Coinfecção/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Hepatite B/epidemiologia , Adolescente , Alanina Transaminase/sangue , Antirretrovirais/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Ásia Sudeste/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Estudos Transversais , DNA Viral/sangue , Bases de Dados Factuais , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/epidemiologia , Humanos , Masculino , Prevalência , Estudos Soroepidemiológicos , Resultado do Tratamento , Adulto Jovem
13.
J Acquir Immune Defic Syndr ; 77(4): 417-426, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29303843

RESUMO

BACKGROUND: HIV-infected children with long-term nonprogressive (LTNP) disease eventually convert to a progressive disease type, yet the extent to which these children experience the cognitive and emotional symptoms observed in typical progressive HIV (Progressors) is unknown. METHODS: Eighty-eight LTNPs, 53 Progressors, and 323 healthy controls completed annual assessments of cognitive and emotional health as part of a prospective study. The 2 HIV-infected groups and the healthy controls were matched on age and sex distribution at enrollment. Plasma HIV RNA, T-cell counts/percentages, activated monocytes, perivascular monocytes, and markers of macrophage activation (sCD163 and sCD14) were compared by progression subtype. Cognitive and emotional outcomes were compared using cross-sectional linear regression analysis and longitudinal sensitivity models. RESULTS: LTNPs exhibited the same cognitive phenotype and emotional dysregulation as Progressors, with worse outcomes in both groups compared with controls. In addition, cognitive and emotional symptoms were evident before children reached the minimum age for LTNP designation (8 years). Baseline plasma HIV RNA, sCD163, activated monocytes, and perivascular monocytes were lower in LTNPs versus Progressors, with no difference in T-cell counts/percentages or sCD14 levels. Most LTNPs converted to a progressive disease subtype during the study, with similar cognitive and emotion profiles between these subgroups. CONCLUSIONS: Pediatric LTNPs experience cognitive and emotional difficulties that mirror symptoms of progressive disease. The abnormalities are present at young ages and persist independent of plasma T-cell counts. The findings highlight the neurodevelopmental risk of pediatric HIV, even in those with early innate disease control.


Assuntos
Infecções por HIV/patologia , Sobreviventes de Longo Prazo ao HIV , Transtornos Mentais/epidemiologia , Saúde Mental , Adolescente , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Criança , Pré-Escolar , Feminino , Infecções por HIV/complicações , Voluntários Saudáveis , Humanos , Lactente , Receptores de Lipopolissacarídeos/sangue , Estudos Longitudinais , Contagem de Linfócitos , Ativação de Macrófagos , Macrófagos/imunologia , Masculino , Transtornos Mentais/patologia , Monócitos/imunologia , Estudos Prospectivos , RNA Viral/sangue , Receptores de Superfície Celular/sangue , Linfócitos T/imunologia , Carga Viral
14.
Pediatr Infect Dis J ; 37(7): 662-668, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29200184

RESUMO

BACKGROUND: Children with vertically acquired HIV exhibit persistent cognitive impairments, yet the corresponding neuroimaging signature of vertical infection remains unclear. METHODS: Fifty healthy control children and 51 vertically infected children were included in the study. The HIV-infected group consisted of survivors who had not received antiretroviral therapy at birth. The HIV-infected group averaged 11.4 (2.5) years of age, with a median CD4 count of 683 cells/mm(3). Most (71%) of the HIV-infected children were on antiretroviral therapy for a median of 34 months (range: 33-42) with HIV RNA <40 copies/mL in 89% of the sample. The HIV-uninfected group averaged 10.6 (2.6) years of age. Magnetic resonance imaging was acquired to determine volumes of the caudate, putamen, thalamus, pallidum, hippocampus, nucleus accumbens, total white matter, total gray matter and cortical gray matter. Correlational analyses examined the degree of shared variance between brain volumes and both cognitive performances and laboratory markers of disease activity (T cells and plasma viral load). RESULTS: HIV-infected children exhibited larger volumes of the caudate, nucleus accumbens, total gray matter and cortical gray matter when compared with the controls. Volumetric differences were predominately evident in children under 12 years of age. HIV-infected children performed worse than controls on most neuropsychologic tests, though neither cognitive performances nor laboratory markers corresponded to brain volumes in the HIV-infected children. CONCLUSIONS: Outcomes of the present study suggest abnormal brain maturation among HIV-infected pediatric survivors. Longitudinal studies of brain integrity and related resilience factors are needed to determine the impact of neuroimaging abnormalities on psychosocial function in pediatric HIV.


Assuntos
Infecções por HIV/complicações , Transmissão Vertical de Doença Infecciosa , Neuroimagem , Testes Neuropsicológicos , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/virologia , Criança , Disfunção Cognitiva/etiologia , Feminino , HIV , Infecções por HIV/psicologia , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Carga Viral
15.
PLoS One ; 12(5): e0176009, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28489856

RESUMO

BACKGROUND: Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials. METHODS: Asymptomatic, HIV-positive, non-breastfeeding women with pre-ART CD4+ T-cell counts ≥ 400 cells/mm3 started on ART during pregnancy were randomized up to 42 days after delivery to continue or discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the preferred ART regimen. The sample size was selected to provide 88% power to detect a 50% reduction from an annualized primary event rate of 2.07%. A post-hoc analysis evaluated HIV/AIDS-related and World Health Organization (WHO) Stage 2 and 3 events. All analyses were intent to treat. RESULTS: 1652 women from 52 sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US were enrolled (1/2010-11/2014). Median age was 28 years and major racial categories were Black African (28%), Asian (25%) White (15%). Median entry CD4 count was 696 cells/mm3 (IQR 575-869), median ART exposure prior to delivery was 19 weeks (IQR 13-24) and 94% had entry HIV-1 RNA < 1000 copies/ml. After a median follow-up of 2.3 years, the primary composite endpoint rate was significantly lower than expected, and not significantly different between arms (continue arm 0.21 /100 person years(py); discontinue 0.31/100 py, Hazard ratio (HR) 0.68, 95% CI: 0.19, 2.40). WHO Stage 2 and 3 events were significantly reduced with continued ART (2.08/100 py vs. 4.36/100 py in the discontinue arm; HR 0.48, 95%CI: 0.33, 0.70). Toxicity rates did not differ significantly between arms. Among women randomized to continue ART, 189/827 (23%) had virologic failure; of the 155 with resistance testing, 103 (66%) failed without resistance to their current regimen, suggesting non-adherence. CONCLUSIONS: Overall, serious clinical events were rare among young HIV-positive post-partum women with high CD4 cell counts. Continued ART was safe and was associated with a halving of the rate of WHO 2/3 conditions. Virologic failure rates were high, underscoring the urgent need to improve adherence in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00955968.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Infecções por HIV/tratamento farmacológico , Período Pós-Parto , Adulto , Farmacorresistência Viral , Feminino , Humanos , Carga Viral
16.
J Adolesc Health ; 61(1): 91-98, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28343759

RESUMO

PURPOSE: To assess the incidence and predictors of postsuppression virologic rebound (VR) among adolescents on stable combination antiretroviral therapy in Asia. METHODS: Perinatally HIV-infected Asian adolescents (10-19 years) with documented virologic suppression (two consecutive viral loads [VLs] <400 copies/mL ≥6 months apart) were included. Baseline was the date of the first VL <400 copies/mL at age ≥10 years or the 10th birthday for those with prior suppression. Cox proportional hazards models were used to identify predictors of postsuppression VR (VL >1,000 copies/mL). RESULTS: Of 1,379 eligible adolescents, 47% were males. At baseline, 22% were receiving protease inhibitor-containing regimens; median CD4 cell count (interquartile range [IQR]) was 685 (448-937) cells/mm3; 2% had preadolescent virologic failure (VF) before subsequent suppression. During adolescence, 180 individuals (13%) experienced postsuppression VR at a rate of 3.4 (95% confidence interval: 2.9-3.9) per 100 person-years, which was consistent over time. Median time to VR during adolescence (IQR) was 3.3 (2.1-4.8) years. Wasting (weight-for-age z-score <-2.5), being raised by grandparents, receiving second-line protease inhibitor-based regimens, starting combination antiretroviral therapy after 2005, and having preadolescent VF were independent predictors of adolescent VR. At VR, median age, CD4 cell count, and VL (IQR) were 14.8 (13.2-16.4) years, 507 (325-723) cells/mm3, and 4.1 (3.5-4.7) log10 copies/mL, respectively. CONCLUSIONS: A modest and consistent incidence of postsuppression VR was documented during adolescence in our cohort. Having poor weight, receiving second-line regimens, and prior VF were associated with an increased VR rate. Adolescents at higher risk of VR may benefit from more intensive VL monitoring to enhance adherence management.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/virologia , Carga Viral , Adolescente , Ásia Sudeste , Criança , Feminino , HIV/isolamento & purificação , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Recidiva
17.
Pediatr Infect Dis J ; 36(4): 401-404, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28005687

RESUMO

We determined hepatitis B virus (HBV) suppression rates among 18 lamivudine (3TC)-experienced HBV-human immunodeficiency virus-coinfected adolescents after treatment with tenofovir disoproxil fumurate (TDF). At TDF initiation, their median age was 17.6 years, and duration of 3TC exposure was 7.3 years. Eleven patients (61%) achieved HBV DNA <60 IU/mL after 48 weeks on TDF and 3TC which was similar to adult studies, although hepatitis B surface antigen loss or hepatitis B envelope antigen seroconversion did not occur.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Tenofovir/uso terapêutico , Adolescente , Adulto , Criança , Coinfecção/epidemiologia , Coinfecção/virologia , DNA Viral/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepatite B/epidemiologia , Hepatite B/virologia , Humanos , Lamivudina/uso terapêutico , Estudos Longitudinais , Estudos Prospectivos , Adulto Jovem
18.
Antivir Ther ; 22(6): 471-479, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27786155

RESUMO

BACKGROUND: This study aimed to determine the effect of tenofovir disoproxil fumarate (TDF) on bone metabolism and bone mass in HIV-infected adolescents. METHODS: This was a sub-study of a cross-sectional multicentre bone health trial that enrolled perinatally HIV-infected Thai and Indonesian adolescents (10-18 years) with viral suppression on antiretroviral therapy. Participants were classified into two groups as TDF users and non-users. Bone metabolism-related markers (25-hydroxyvitamin D [25-OHD], intact parathyroid hormone [iPTH], bone turnover biomarkers), and lumbar spine dual-energy X-ray absorptiometry were assessed. Bone mineral density (BMD)/bone mineral apparent density (BMAD) Z-scores were calculated. RESULTS: Of 394 adolescents, 136 (34.5%) and 258 (65.5%) were TDF users and non-users, respectively. Among TDF users, median age (IQR) was 16.1 (14.7-17.4) years and TDF treatment duration (IQR) was 2.3 (1.4-3.1) years. Among TDF non-users, median age (IQR) was 14.3 (12.6-16.4) years. BMD and BMAD Z-scores comparing TDF users with non-users were -0.8 and -0.6 (P=0.27), and -0.3 and -0.2 (P=0.58), respectively. The association between TDF use and iPTH elevation was intensified in adolescents with suboptimal vitamin D levels (25-OHD <30 ng/ml; P=0.001). TDF administration was positively associated with bone resorption marker (P=0.04) and negatively associated with bone formation marker (P=0.04). With data up to 4 years, neither association between TDF use and bone mass loss (BMD: P=0.09; BMAD: P=0.22), nor variation of bone mass Z-scores by TDF treatment duration (BMD: P=0.34; BMAD: P=0.58) was demonstrated. CONCLUSIONS: Recent TDF administration was correlated with PTH elevation and bone turnover dysregulation but not with bone mass reduction in our cohort. A study with extended follow-up to ascertain TDF-associated bone mass deterioration is warranted.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Infecções por HIV/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal , Tenofovir/farmacologia , Tenofovir/uso terapêutico , Adolescente , Terapia Antirretroviral de Alta Atividade , Biomarcadores , Contagem de Linfócito CD4 , Criança , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Humanos , Testes de Função Renal , Masculino , Gravidez , Índice de Gravidade de Doença
19.
PLoS One ; 11(12): e0165866, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27906980

RESUMO

INTRODUCTION: The rural areas of Northern Thailand are home to a large cultural diversity of ethnic minority groups. Previous studies have shown that young people in rural Thailand have low levels of knowledge on HIV/AIDS and high sexual risks. We compared sexual behaviors between the lowland Thai youth and the youth from ethnic minority groups. METHODS AND FINDINGS: This is a cross-sectional quantitative study conducted among high-school Thai and ethnic students in Chiang Mai. From a total 1215 participants, 487 (40.1%) were lowland Thai and 728 (59.9%) were from ethnic minorities. Overall, 17.9% of respondents reported "ever had sex." Lowland Thai adolescents were more likely to have ever had sex compared with ethnic minority adolescents (AOR, 1.61; CI, 1.06-2.45; P< 0.01). A higher proportion of lowland Thai respondents reported having ≥ 2 lifetime sexual partners (51.9% vs. 33.3%, P = 0.003), or currently having a boy/girlfriend (59.9% vs. 45.3%, P< 0.001) compared to ethnic minority adolescents. Consistent condom use was low in both groups (22.6%). The common significant factors associated with "ever had sex" in both groups were "ever drunk alcohol in the past year" and "currently having a boy/girlfriend." Specifically, for lowland Thai youth, being around the age of 17 or 18 years and "ever used methamphetamine in the past year" were associated with increased odds of "ever had sex". For ethnic minority adolescents, being female and belonging to religions other than Buddhism were associated with decreased odds of "ever had sex". CONCLUSION: A substantially higher proportion of lowland Thai engage in risky sexual behaviors when compared to ethnic minorities. However, both groups remained vulnerable to HIV and other sexually transmitted infections. To minimize sexual risks, education program and school-based interventions are warranted to increase awareness of young people about risky behaviors and to promote essential life skills.


Assuntos
Infecções por HIV/epidemiologia , Comportamento Sexual/psicologia , Doenças Sexualmente Transmissíveis/epidemiologia , Adolescente , Alcoolismo/epidemiologia , Feminino , Infecções por HIV/transmissão , Humanos , Masculino , Metanfetamina/efeitos adversos , Grupos Minoritários , População Rural , Sexo Seguro , Comportamento Sexual/fisiologia , Parceiros Sexuais , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
20.
Ther Drug Monit ; 38(6): 791-795, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27749514

RESUMO

BACKGROUND: Failure rates of second-line boosted protease inhibitor antiretroviral therapy regimens in children rise over time. Therapeutic drug monitoring can contribute to assessments of adherence. The authors assessed the performance characteristics of the US DHHS-recommended lopinavir (LPV) concentration of 1.0 mg/L for predicting virologic failure (VF) and intermediate- to high-level LPV resistance in Asian children. METHODS: LPV concentration, HIV RNA level, and adherence data from study participants in Thailand, Vietnam, and Indonesia receiving second-line LPV-based ART and followed for ≥24 weeks were analyzed. RESULTS: A total of 223 children at a median age of 10.4 (interquartile range, 7.9-13.4) years were enrolled, and 61% of them were male. Their mean CD4 was 842 ± 438 cells per cubic millimeter, and the median LPV duration was 2.5 (interquartile range, 1.3-4.2) years. Five of 84 (6%) and 18 of 139 (13%) children had LPV trough and random concentrations <1.0 mg/L at study week 24. Using either of these trough or random LPV concentrations, a cutoff at 1.0 mg/L gave an area under the receiver operating characteristics curve of 0.69 in predicting VF with sensitivity of 44% (95% CI 23-66) and specificity of 94% (95% CI 89-97). Seven of 21 with VF and resistance results available had ≥1 major protease inhibitor mutation. Multivariate logistic regression found LPV concentrations <1.0 mg/L (odds ratio, 6.47; 95% CI 2.15-19.50, P = 0.001) and CD4 ≤20% (odds ratio, 2.83; 95% CI 1.01-7.89, P = 0.05) were independently associated with HIV RNA >1000 copies per milliliter. No factors predicted major LPV resistance mutations. CONCLUSIONS: The authors support that the DHHS target LPV concentration of <1.0 mg/L is predictive of VF, but not of the presence of major LPV mutations.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lopinavir/uso terapêutico , Adolescente , Ásia , Criança , Monitoramento de Medicamentos/métodos , Feminino , HIV-1/efeitos dos fármacos , Humanos , Masculino , Carga Viral/efeitos dos fármacos
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