Évolution à long terme des lipides chez des patients Thaïlandais infectés par le VIH sous traitement

Le traitement par éfavirenz, un médicament antirétroviral, a été associé avec des changements de profil lipidique potentiellement défavorables. Ce travail a abordé la question de savoir si ces effets dépendent des concentrations plasmatiques d’éfavirenz et, dans ce cas, si sa posologie pourrait être optimisée sans perte d'efficacité.Un modèle de pharmacocinétique de population a été développé à partir de données d’enfants infectés par le VIH. La simulation d’une population normalisée sous éfavirenz aux posologies recommandées montre que 15 % des enfants auraient des concentrations insuffisantes 12 heures après la prise, ce qui serait associé à un risque de la réplication virale de 23 %.Pour décrire la relation entre taux plasmatiques d'éfavirenz et changements de taux de cholestérol, des modèles de pharmacocinétique-pharmacodynamique (PK-PD) de réponse indirecte ont été développés. Le modèle sélectionné prédit que les taux d’éfavirenz individuels sont associés à une augmentation des lipoprotéines de haute densité sur 5 ans, et des lipoprotéines de basse densité durant 4 mois avec un retour progressif aux valeurs de base.Pour évaluer l’impact des concentrations d'éfavirenz sur l'efficacité, un modèle dynamique PK-PD a décrit la relation entre ces concentrations et l’évolution de la charge virale VIH et du taux de CD4. Un score d’efficacité a été développé sur la base d’hypothèses pharmacodynamiques pour prédire le risque de la réplication virale.L’utilisation de l’éfavirenz aux posologiques recommandées par la Food and Drug Administration aux Etats-Unis semble assurer une efficacité optimale et des changements potentiellement favorables dans les fractions de cholestérol.As other antiretroviral drugs, treatment with efavirenz has been associated with potentially unfavorable lipid profile changes in adults and in children. The thesis addressed the question of whether these changes depend on efavirenz plasma concentrations and if dose adjustments could be envisioned without loss of efficacy.To estimate individual efavirenz exposure over 24 hours, a population pharmacokinetic model was developed using data from HIV infected children. Simulations for a normalized population receiving efavirenz dosed according recommendations predicted that 15% of children would have insufficient mid dose concentrations, associated with a 23% risk of viral replication.To describe the relationship between efavirenz concentrations and cholesterol changes, population pharmacokinetic-pharmacodynamic (PK-PD) indirect response models were developed. The selected model predicted that individual efavirenz concentrations were associated with an increase in high-density lipoprotein concentrations over 5 years but with an increase in low-density lipoprotein concentrations only during the first 4 months of treatment followed by a gradual return to baseline.To study the importance of efavirenz concentrations with regard to efficacy, a PK-PD dynamics model was developed to describe the relationship between concentrations and HIV RNA load and CD4 cell count evolutions. A score was defined based on a pharmacodynamic hypothesis to predict the risk of viral replication.Using US Food and Drug Administration dosing recommendations in children ensure optimal efficacy and potentially favorable changes in cholesterol fractions

Overweight and Obesity Coexist with Thinness among Lao’s Urban Area Adolescents

Introduction. In recent decades, the developing countries of Southeast Asia, including the Lao People’s Democratic Republic (Lao PDR), have experienced a rapid growth of their urban population. Partly as a result of that, issues of undernutrition and overnutrition became a significant public health problem. Objective. To examine the prevalence of overweight and obesity and their related factors, among the school-attending adolescents in the Lao capital of Vientiane. Methods. A cross-sectional data on 300 adolescents aged 15–19 were collected during the months of March, April, and May 2018 by means of a self-administrated questionnaire. Anthropometric measurements were used to obtain data on height and weight. Pearson’s chi-squared test, Fisher exact tests, and univariable and multivariable logistic regressions were applied in the course of the statistical analysis. Results. The study found a high prevalence of overweight/obesity (23.3%) and thinness (10.3%). Poor eating habits were noted in 67.0% of adolescents, even though 78.0% of them had a good knowledge of nutrition. Factors significantly associated with the overweight/obesity were low physical activities (aOR = 18.3; 95% CI: 5.51–60.66) and adolescents living with their guardians (aOR = 0.25; 95% CI: 0.08–0.79). Results also indicated that, in 47.3% of the cases, teachers, acting as a source of health and nutrition information, can prevent the risk of adolescents’ overweight/obesity (aOR = 2.05, 95% CI = 1.11–3.80) but not their thinness (aOR = 0.4, 95% CI = 0.17–0.88). Conclusions. Laotian adolescents are facing the spectrum of malnutrition in urban areas. To improve adolescents’ nutritional status, there is a need for a collaborative approach of public health agencies that would address the issues of an effective food and nutrition policy. The school curricula should also include programs on nutrition and physical education

Longitudinal measurements of neutrophil-to-lymphocyte ratio in nasopharyngeal cancer treated with concurrent chemoradiotherapy.

ObjectiveWe study factors affecting neutrophil-to-lymphocyte ratio (NLR) and its changes throughout the treatment (ΔNLR) of nasopharyngeal carcinoma (NPC) underwent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy (AC) and oncological outcomes including overall survival (OS) and disease-free survival (DFS).MethodsData from 81 NPC patients was retrospectively evaluated. NLRs were obtained from first week of CCRT (pre-CCRT), last week of CCRT (end-CCRT), and at last cycle of AC (end-AC). Pre-CCRT NLR was categorized into "low" and "high". End-CCRT and end-AC ΔNLRs were divided into "increased" and "decreased" based on NLR at these two timepoints relative to the value at pre-CCRT. Associations between sex, age, cancer stage and NLR, ΔNLRs were investigated. OS and DFS were reported.ResultsMedian NLR at pre-CCRT (2.47) was lower than NLR at end-CCRT (6.29) and end-AC (3.77) (P-value = 0.043). Advanced cancer stage associated with high pre-CCRT NLR (P-value = 0.047). Male gender was associated with "increased" end-CCRT ΔNLR, whereas male gender and age ≤51 were associated with "increased" end-AC ΔNLR. Three-year OS and DFS rates were 85.25% and 76.39%, respectively. There were no statistically significant differences observed in OS and DFS among groups categorized by pre-CCRT NLR, ΔNLRs, gender, age, and cancer stage.ConclusionsNLR increases during NPC treatment. Advanced staging is associated with higher baseline NLR. Increased ΔNLR is associated with male gender at end-CCRT and male gender with age ≤51 years at end-AC. No relation between NLR and its dynamic change with either OS or DFS was demonstrated

Detection of Electroencephalographic Abnormalities and Its Associated Factors among Children with Autism Spectrum Disorder in Thailand

Epilepsy often causes more severe behavioral problems in children with autism spectrum disorder (ASD) and is strongly associated with poor cognitive functioning. Interestingly, individuals with ASD without a history of epilepsy can have abnormal electroencephalographic (EEG) activity. The aim of this study was to examine associations between EEG abnormalities and the ASD severity in children. The children with ASD who enrolled at the Rajanagarindra Institute of Child Development, Thailand were included in this study. The severity of ASD was measured by interviewing their parents with the Thai autism treatment evaluation checklist. The short sensory profile checklist was used for screening the abnormality of children in each domain. Ordinal logistic regression analysis was used to examine associations between factors potentially linked to EEG abnormalities. Most of the study participants were boys (87.5%) and the median age was 5 years. Among the 128 children, 69.5% showed EEG abnormalities (41.4% slow-wave and 28.1% epileptiform-discharge). The results show that a larger number of symptoms and increased severity of ASD were independently associated with a higher risk of EEG abnormalities. Our results emphasize the need for guidelines on the presence of EEG abnormalities in children with ASD for the early detection of epilepsy and improving treatment outcomes

A comparative study of transgender women accessing HIV testing via face-to-face and telemedicine services in Chiang Mai, Thailand during the COVID-19 pandemic and their risk of being HIV-positive

Abstract Background Due to the restricted availability of health services in Thailand, there are still some transgender women (TGW) who do not have access to HIV counseling and testing. Telehealth, which is accessible to individuals who are reluctant to undergo face-to-face interviewing, played an especially important role during the COVID-19 epidemic. The objectives of this study are to compare the characteristics, pattern of accessing HIV testing, and the HIV-positive rates of TGW between the face-to-face and telemedicine services. Methods We conducted a cross-sectional study to compare the access to HIV testing and the HIV-positive rates among TGW via face-to-face service and telemedicine services and examined the influence of potential associated factors on the risk of being HIV-positive. Results Of the 637 TGW participants, 26 (4.1%) were HIV-positive. Accessing the telemedicine service increased in the third and fourth COVID-19 waves (28.1% in the first and second vs. 71.9% in the third and fourth). There was no difference in the risk of being HIV-positive between the types of service. Having sex work experience (adjusted odds ratio (aOR) = 5.92; 95% confidence interval (CI): 1.57–22.30) and either never having been or tested more than 1 year ago were independently significantly associated with a higher risk of being HIV-positive (aOR = 4.05; 95% CI: 1.11–14.77). Conclusion The telemedicine service became more popular among TGW during the COVID-19 pandemic and was not related to a higher risk of being HIV-positive. Moreover, it proved to be an effective alternative channel to access HIV testing, especially for intravenous drug users. Sex work experience and irregular HIV testing are key risk factors for HIV infection in TGW seeking either the telemedicine or face-to-face service

Role of efavirenz plasma concentrations on long-term HIV suppression and immune restoration in HIV-infected children.

BackgroundTo access the long term relationship between efavirenz plasma concentrations and evolution of HIV RNA loads and CD4 cell counts in children.MethodsRetrospective analysis of data from HIV-infected children on first line efavirenz-containing regimen. A population pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the evolution of HIV RNA load and CD4 cell count (efficacy outcomes) in relation to efavirenz plasma concentration. Individual CYP2B6 516 G>T genotype data were not available for this analysis. A score (ISEFV) quantifying the effect of efavirenz concentrations on the long-term HIV replication was calculated from efavirenz concentrations and PD parameters and, a value of ISEFV below which HIV replication is likely not suppressed was determined. Cox proportional hazards regression models were used to assess the association of the risk of viral replication with ISEFV, and with efavirenz mid-dose concentration(C12).ResultsAt treatment initiation, median (interquartile range, IQR) age was 8 years (5 to 10), body weight 17 kg (14 to 23), HIV RNA load 5.1 log10 copies/mL (4.6 to 5.4), and CD4 cell count 71 cells/mm3. A model of PK-PD viral dynamics assuming that efavirenz decreases the rate of infected host cells adequately described the relationship of interest. After adjusting for age, baseline HIV RNA load and CD4 cell counts an ISEFV ConclusionThe ISEFV score was a good predictor of viral replication in children on efavirenz-based treatment

A Population Pharmacokinetic/Pharmacodynamic Model Predicts Favorable HDL Cholesterol Changes Over the First 5 Years in Children Treated with Current Efavirenz-Based Regimens

Efavirenz use is associated with changes in cholesterol concentrations but it is unclear whether this effect is related to drug concentrations. Using efavirenz and cholesterol plasma concentrations measured in 87 antiretroviral naive children in Thailand, we assessed indirect response models to describe the evolution of high- and low-density lipoprotein cholesterol (HDL, LDL) concentrations in relation to efavirenz plasma concentrations over time where efavirenz was assumed to either stimulate cholesterol production or inhibit its elimination. Simulations of cholesterol evolution for children with different average efavirenz concentrations (Cav ) according to their assumed status of 'fast' or 'slow' metabolizers of efavirenz were performed. At treatment initiation, children's median (interquartile range, IQR) age was 8 years (5 to 10), body mass index z-score 0.01 (-1.05 to 1.44), HDL 31 mg/dL (24 to 44) and LDL 83 mg/dL (69 to 100). Median (IQR) efavirenz Cav was 1.7 mg/L (1.3 to 2.1) during the period of observation. The best model describing the evolution of HDL and LDL cholesterol concentrations over time assumed that efavirenz inhibited their elimination. HDL concentrations increase over 5 years while LDL concentrations only increased during the first 4 months and then returned to baseline levels afterwards. Simulations predicted that, after 3 years, HDL would increase to 63 mg/dL in 'fast' metabolizers and 97 mg/dL in 'slow' metabolizers of efavirenz. The population pharmacokinetic-pharmacodynamic (PK-PD) model shows that favorable HDL cholesterol changes can be expected in children with current efavirenz dosing guidelines over 5 years of treatment. This article is protected by copyright. All rights reserved