Etravirine with 2 NRTIs: an effective switch option for ARV simplification and side effect management

Etravirine (ETV) has been approved for use in treatment-experienced patients based on results of the Duet clinical trials [1]. Less experience exists with ETV in earlier stages of treatment. ETV has a favorable genetic barrier, lipid profile, and little associated CNS toxicity. These characteristics make ETV attractive as a switch strategy for simplification and/or management of side effects. A retrospective chart review was conducted at a large urban HIV clinic in Toronto. All patients who were switched to ETV plus 2 nucleosides and whose viral load (VL) was <200 copies/ml at the time of switch were included. Maintenance of viral suppression, CD4 and lipid changes at 24 weeks and reason for switch to ETV are reported. Seventy-three patients (67 male) were identified. Mean age was 46±10 and mean duration of HIV infection was 11.7±7.4 years. Switches were from efavirenz=29, atazanavir=23, lopinavir=16, other=5. Duration of prior regimen was long; median 195 weeks. CNS and GI intolerance were the most common reasons for switches. At the time of analysis, 63 patients had reached week 24. Three patients had discontinued ETV prior to week 24, 3 LTF/U, 4 had <24 weeks follow-up. 92% (67/73) maintained VL suppression (ITT); failures were 6 patients who stopped/lost-to-follow-up prior to week 24. On treatment, CD4 increased and lipid decreased changes as seen below. All patients who switched due to CNS side effects had subjective improvement.Switch to ETV plus 2 nucleosides maintained viral suppression, improved lipid profiles and improved side effect profile in this selected group of patients. 48 week f/u will be presented

Urban Climate Action. The urban content of the NDCs: Global review 2022

This report was prepared by United Nations Human Settlement Programme (UN-Habitat) and the UNESCO Chair on Urban Resilience at the University of Southern Denmark (SDU.Resilience). It offers a global analysis of the urban content of 193 Nationally Determined Contributions (NDCs) submitted to the Secretariat of the United Nations Framework Convention on Climate Change (UNFCCC) before the 19th of June 2022. For this report, more than 200 indicators were used to analyse external data (e.g., Human Development Index and income categorisation) and data within the NDCs, including climate mitigation and adaptation challenges and responses, as well as specific sectors. This analysis is instrumental to supporting Parties’ efforts in further integrating national climate policies and urban climate actions, which is considered fundamental to raising ambition and developing adequate and timely actions as required by the current climate emergency. This review can be instrumental for advocacy and direct support to countries by partner organisations. The work was supported by a group of experts from bilateral and multilateral organisations and academia. Three expert group meetings were convened, and a peer review was organised for the final report

Recent Advances in Graph Partitioning

We survey recent trends in practical algorithms for balanced graph partitioning together with applications and future research directions

Phase IIa Global Study Evaluating Rituximab for the Treatment of Pediatric Patients With Granulomatosis With Polyangiitis or Microscopic Polyangiitis

OBJECTIVE: To assess the safety, tolerability, pharmacokinetics, and efficacy of rituximab (RTX) in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). METHODS: The Pediatric Polyangiitis Rituximab Study was a phase IIa, international, open-label, single-arm study. During the initial 6-month remission-induction phase, patients received intravenous infusions of RTX (375 mg/m2 body surface area) and glucocorticoids once per week for 4 weeks. During the follow-up period, patients could receive further treatment, including RTX, for GPA or MPA. The safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy outcomes with RTX were evaluated. RESULTS: Twenty-five pediatric patients with new-onset or relapsing disease were enrolled at 11 centers (19 with GPA [76%] and 6 with MPA [24%]). The median age was 14 years (range 6-17 years). All patients completed the remission-induction phase. During the overall study period (≤4.5 years), patients received between 4 and 28 infusions of RTX. All patients experienced ≥1 adverse event (AE), mostly grade 1 or grade 2 primarily infusion-related reactions. Seven patients experienced 10 serious AEs, and 17 patients experienced 31 infection-related AEs. No deaths were reported. RTX clearance correlated with body surface area. The body surface area-adjusted RTX dosing regimen resulted in similar exposure in both pediatric and adult patients with GPA or MPA. Remission, according to the Pediatric Vasculitis Activity Score, was achieved in 56%, 92%, and 100% of patients by months 6, 12, and 18, respectively. CONCLUSION: In pediatric patients with GPA or MPA, RTX is well tolerated and effective, with an overall safety profile comparable to that observed in adult patients with GPA or MPA who receive treatment with RTX. RTX is associated with a positive risk/benefit profile in pediatric patients with active GPA or MPA