Pharmacokinetics of Generic Pediatric Dolutegravir Dispersible Tablet in Thai Young Children Living With HIV Weighing Below Twenty Kilograms.

INTRODUCTION: Dolutegravir (DTG) dispersible tablet (DTG-DT) is a pediatric-friendly formulation. We aimed to describe the pharmacokinetics and virologic responses of generic DTG-DT in children weighing <20 kg. METHODS: Children living with HIV-1 and <7 years of age weighing 6 to <20 kg were eligible. A generic 10-mg scored DTG-DT was administered to children using 3 weight bands (WB): WB1 (6 to <10 kg), WB2 (10 to <14 kg) and WB3 (14 to <20 kg), at doses of 20 mg (higher than World Health Organization recommendation of 15 mg), 20 mg and 25 mg, respectively. Steady-state intensive pharmacokinetics (PK) was performed in fasting condition with blood sampling at predose and 1, 2, 3, 4, 6 and 24 hours postdose. DTG PK parameters were estimated using a noncompartmental analysis, and DTG trough concentrations (C 24 ) and 24-hour area under the concentration-time curve were calculated. Comparisons were made with ODYSSEY and IMPAACT 2019. And 90% effective concentration of 0.32 mg/L was used as a reference individual DTG C 24 concentration. RESULTS: From August 2021 to March 2023, 29 Thai children with a median (interquartile range) age of 3.2 (1.5-4.8) years were enrolled; 8 in WB1, 9 in WB2 and 12 in WB3. All children were treatment experienced and 59% had HIV RNA <200 copies/mL. Overall geometric mean (coefficient of variation percentage) DTG C 24 was 1.0 (46%) mg/L [WB1, 0.9 (53%); WB2, 0.9 (27%); WB3, 1.2 (51%)]. Geometric mean (coefficient of variation percentage) 24-hour area under the concentration-time curve was 83.2 (24%) mg h/L [WB1, 84.3 (31%); WB2, 76.9 (16%); WB3, 87.6 (25%)]. At weeks 24 and 48, 90% and 92% of participants had plasma HIV RNA <200 copies/mL. CONCLUSIONS: Generic DTG-DT provided adequate drug exposure in children weighing 6 to <20 kg. The exploratory dose of DTG 20 mg for children weighing 6 to <10 kg showed similar PK parameters to World Health Organization doses in the other WB.

Pharmacokinetics of Generic Pediatric Dolutegravir Dispersible Tablet in Thai Young Children Living With HIV Weighing Below Twenty Kilograms.

INTRODUCTION: Dolutegravir (DTG) dispersible tablet (DTG-DT) is a pediatric-friendly formulation. We aimed to describe the pharmacokinetics and virologic responses of generic DTG-DT in children weighing <20 kg. METHODS: Children living with HIV-1 and <7 years of age weighing 6 to <20 kg were eligible. A generic 10-mg scored DTG-DT was administered to children using 3 weight bands (WB): WB1 (6 to <10 kg), WB2 (10 to <14 kg) and WB3 (14 to <20 kg), at doses of 20 mg (higher than World Health Organization recommendation of 15 mg), 20 mg and 25 mg, respectively. Steady-state intensive pharmacokinetics (PK) was performed in fasting condition with blood sampling at predose and 1, 2, 3, 4, 6 and 24 hours postdose. DTG PK parameters were estimated using a noncompartmental analysis, and DTG trough concentrations (C24) and 24-hour area under the concentration-time curve were calculated. Comparisons were made with ODYSSEY and IMPAACT 2019. And 90% effective concentration of 0.32 mg/L was used as a reference individual DTG C24 concentration. RESULTS: From August 2021 to March 2023, 29 Thai children with a median (interquartile range) age of 3.2 (1.5-4.8) years were enrolled; 8 in WB1, 9 in WB2 and 12 in WB3. All children were treatment experienced and 59% had HIV RNA <200 copies/mL. Overall geometric mean (coefficient of variation percentage) DTG C24 was 1.0 (46%) mg/L [WB1, 0.9 (53%); WB2, 0.9 (27%); WB3, 1.2 (51%)]. Geometric mean (coefficient of variation percentage) 24-hour area under the concentration-time curve was 83.2 (24%) mg h/L [WB1, 84.3 (31%); WB2, 76.9 (16%); WB3, 87.6 (25%)]. At weeks 24 and 48, 90% and 92% of participants had plasma HIV RNA <200 copies/mL. CONCLUSIONS: Generic DTG-DT provided adequate drug exposure in children weighing 6 to <20 kg. The exploratory dose of DTG 20 mg for children weighing 6 to <10 kg showed similar PK parameters to World Health Organization doses in the other WB.

Serum lactate and lactate dehydrogenase as parameters for the prediction of dengue severity.

BACKGROUND: Lactate and lactate dehydrogenase (LDH) have been found to be elevated in cardiopulmonary failure, sepsis, shock and hepatic injury. Severe dengue hemorrhagic fever (DHF) patients also develop shock and experience a certain degree of hepatic injury, implicating that serum lactate and LDH may be elevated in Dengue shock syndrome (DSS). OBJECTIVE: To determine serum lactate and LDH levels in dengue patients to see whether they can be used as predictors of severe dengue cases. MATERIAL AND METHOD: A cross sectional study was conducted on suspected dengue patients admitted to the dengue ward, Queen Sirikit National Institute of Child Health (QSNICH), between May 2011 and February 2012. Laboratory tests were used to confirm dengue cases in the enrolled patients. Blood for serum lactate was drawn in patients every day after enrollment. Blood for LDH and liver function test (LFT) were drawn 3 times: enrollment day, day of leakage, and discharge day. Lactate and LDH levels are compared among dengue and non-dengue patients. Dengue fever (DF), DHF and DSS patients were classified according to the WHO 1997 dengue classification. RESULTS: 253 patients were enrolled, comprising of 120 DF, 75 DH, 30 DSS, and 28 non-dengue patients. The majority of dengue patients had liver impairment, demonstrated by elevated aspartate aminotransferase (AST) (94.9%) and alanine aminotransferase (ALT) levels (68.6%) while non-dengue patients have minimal elevation. Serum lactate levels were not elevated in the early stages in dengue patients, but were elevated in non-dengue patients. The mean serum lactate levels in DSS patients increased towards the end of febrile phase and reached maximum values on Day 0 (2.2 U/L). On the other hand, serum lactate levels were found to be decreasing in the non-dengue group. The mean serum lactate levels on Day 0 was found to be different in DSS patients (2.26 U/L) compared to DF 1.63 U/L), DHF (1.79 U/L) and non-dengue patients (1.68 U/L) (p < 0.05). Mean serum LDH levels were elevated in the early stages of the disease in all groups of patients, but with different levels. Mean serum LDH levels was 709.2 in DF, 1,873 in DHF, 654.5 in DSS, and 434 IU in non-dengue patients. The mean LDH levels in dengue patients were > 500 IU, while it was < 500 IU in non-dengue patients. The increasing mean levels of LDH towards the end of febrile phase were only seen in DHF and DSS patients, but not in DF and non-dengue patients. The mean levels of LDH on Day 0 in DHF, DSS, DF and non-dengue patients are 1,060.7, 1,180.7, 787.2, and 423.8 IU, respectively. CONCLUSION: Serum lactate and LDH was found to be elevated in DHF and/or DSS patients. Lactate may be used as a predictor of DSS if the level is > 2 U/L on Day 0. LDH can be used to differentiate patients with or without dengue in the early febrile phase, if the level is > 500 IU. If the level of LDH is increased to approximately 1, 000 IU on Day 0, it may be a predictor of severe dengue infection or DHF and DSS with plasma leakage.

Invasive Vibrio cholerae non-O1 non-0139 infection in a thalassemic child.

Invasive, extra-intestinal infection with Vibrio cholerae non-O1, non-O139 is rare especially among children. Herein the authors report a 12-year-old girl with underlying beta-thalassemia status post-splenectomy presenting with V. cholerae non-O1, non-O139 gastroenteritis with concomitant septicemia. The pathogen was identified from stool and blood culture and the patient recovered uneventfully after antimicrobial and supportive therapy. A review and comparison of clinical manifestations and outcomes with the previous four cases of invasive V. cholerae non-O1, non-O139 in postsplenectomy thalassemic pediatric patients is reported.