Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption

Objective: Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. Design: Children previously randomized to continuous (continuous ART, n=41) vs. planned treatment interruption (PTI, n=47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale ( 6517 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (<7 for neurocognition and <70 for QoL tests). Results: Characteristics were similar between arms with a median age of 12.6 years, CD4 + of 830 cells/\u3bcl and HIV RNA of 1.7 log 10 copies/ml. The median cumulative ART exposure was 9.6 in continuous ART vs. 7.7 years in PTI (P=0.02). PTI children had a median of 12 months off ART and had resumed ART for 25.2 months at time of first assessment. Neurocognitive scores were similar between arms for all tests. Physical and psychological QoL scores were no different. About 40% had low neurocognitive and QoL scores indicating clinical concern. Conclusion: No differences in information processing speed, sustained attention, short-term memory and QoL functioning were observed between children previously randomized to continuous ART vs. PTI in the PENTA 11 trial

Pharmacokinetics of pediatric lopinavir/ritonavir tablets in children when administered twice daily according to FDA weight bands

Contains fulltext : 136012.pdf (publisher's version ) (Closed access)BACKGROUND: Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval and only body surface area by the EMA. This can lead to a different recommended dose. In addition, weight band-based dosing has not been formally studied in the target population. We evaluated the pharmacokinetics (PK) of LPV/r in children, administered twice daily according to the FDA weight bands, using pediatric tablets. METHODS: Fifty-three HIV-infected children were included in the PK substudy of the Paediatric European Network for the Treatment of AIDS 18 trial (KONCERT). In this study, children were randomized to receive LPV/r twice or once daily, according to FDA weight bands. A PK assessment was performed in 17, 16 and 20 children in the 15-25 kg, >/=25-35 kg and >35 kg weight band, respectively, while children took the tablets twice daily. Rich sampling was performed, and PK parameters were calculated by noncompartmental analysis. Given the high percentage of Asian children, it was also tested whether there was a difference in PK parameters between Asian and non-Asian children. RESULTS: For the total group, LPV geometric mean AUC0-12, Cmax and C12 were 106.9 h x mg/L, 12.0 mg/L and 4.9 mg/L, respectively. There were no significant differences in LPV PK parameters between the weight bands. In addition, weight was not found to be associated with variability in Cmax, C12 or AUC0-12 for the LPV PK parameters. CONCLUSIONS: FDA weight band-based dosing recommendations provide adequate exposure to LPV when using LPV/r pediatric tablets