RESUMEN
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.
RESUMEN
INTRODUCTION: We developed an 18-month Happy Teen 2 (HT2) programme comprised of a one-day workshop, two half-day sessions, and three individual sessions to prepare HIV-infected youth for the transition from paediatric to adult HIV care services. We describe the programme and evaluate the change in youth's knowledge scores. METHODS: We implemented the HT2 programme among HIV-infected Thai youth aged 14-22 years who were aware of their HIV status and receiving care at two hospitals in Bangkok (Siriraj Hospital, Queen Sirikit National Institute of Child Health [QSNICH]). Staff interviewed youth using a standardized questionnaire to assess HIV and health-related knowledge at baseline and at 12 and 18 months while they participated in the programme. We examined factors associated with a composite knowledge score ≥95% at month 18 using logistic regression. RESULTS: During March 2014-July 2016, 192 of 245 (78%) eligible youth were interviewed at baseline. Of these, 161 (84%) returned for interviews at 12 and 18 months. Among the 161 youth, the median age was 17 years, 74 (46%) were female, and 99% were receiving antiretroviral treatment. The median composite score was 45% at baseline and increased to 82% at 12 months and 95% at 18 months (P < 0.001). The range of median knowledge scores for antiretroviral management, HIV monitoring, HIV services, and family planning significantly increased from baseline (range 0-75%) to (range 67-100%) at 12 months and to 100% at 18 months (P < 0.001). Almost all youth were able to describe education and career goals at 12 and 18 months compared to 75% at baseline. In multivariable analysis, a composite knowledge score at 18 months >95% was associated with education level >high school (aOR: 2.15, 95%CI, 1.03-4.48) and receipt care at QSNICH (aOR: 2.43, 95%CI, 1.18-4.98). Youth whose mother and father had died were less likely to have score ≥95% (aOR: 0.22, 95%CI, 0.07-0.67) than those with living parents. CONCLUSIONS: Knowledge useful for a successful transition from paediatric to adult HIV care increased among youth participating in the HT2 programme. Youth follow-up will continue to assess the impact of improved knowledge on outcomes following the transition to adult care services.
