Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy

An observational study of initial HIV RNA decay following initiation of combination antiretroviral treatment during pregnancy.

BACKGROUND: In pregnancy, reduction of HIV plasma viral load (pVL) for the prevention of vertical transmission is time-constrained. The study primary objective is to investigate factors associated with faster initial HIV RNA half-life decay when combination antiretroviral treatment (cART) is initiated in pregnancy. METHODS: This was a multicentre, retrospective, observational study, conducted in south England, United Kingdom, between August 2001 and February 2018. Data were extracted from case notes of eligible women initiating cART during the index pregnancy. Anonymised data were collated and analysed centrally. Regression analyses were conducted to determine factors associated with faster HIV RNA half-life decay in the first 14 days after commencing cART (first-phase), and with achieving an undetectable maternal pVL by 36 weeks' gestation. We then assessed whether HIV- and obstetric- related parameters differed by antiretroviral third agent class and whether the proportions of women with undetectable pVL at 36 weeks' gestation and at delivery differed by antiretroviral third agent class. RESULTS: Baseline pVL was the only independent factor associated with faster first-phase HIV RNA half-life decay on commencing cART. Lower pVL on day 14 after starting cART was associated with an increased likelihood of achieving an undetectable pVL by 36 weeks' gestation. Integrase inhibitor-based cART was associated with a faster first-phase HIV RNA half-life decay on commencing cART. Overall, 73% and 85% of women had an undetectable pVL at 36 weeks' gestation and at delivery respectively, with no significant difference by antiretroviral third agent class. CONCLUSIONS: Only high baseline pVL independently contributed to a faster rate of first-phase viral half-life decay. pVL at 14 days after initiating cART allows early identification of treatment failure. In the first 14 days after initiating cART in pregnancy, integrase inhibitor-based cART reduced maternal pVL faster than protease inhibitor- and non-nucleoside reverse transcriptase-based cART. While our study findings support INSTI use when initiated in pregnancy especially when initiated at later gestations and in those with higher baseline pVL, other non-INSTI based cART with more data on safety in pregnancy also performed well

Pregnancy Management in HIV Viral Controllers: Twenty Years of Experience.

(1) Background: The evidence base for the management of spontaneous viral controllers in pregnancy is lacking. We describe the management outcomes of pregnancies in a series of UK women with spontaneous HIV viral control ( 50 copies/mL) in 14/49 pregnancies (29%) (median 92, range 51-6084). Neonatal ZDV post-exposure prophylaxis was recorded for 45/49 infants. No transmissions were reported. (4) Conclusion: UK practice has been influenced by the change in guidelines, but this has had little impact on CS rates

A New Strategy for Providing Definitions in Task-Oriented Dialogues

Definitions may be made up of one or more components, which correspond to strategic predicates. The selection of which components to use in giving a definition in a task-oriented dialogue depends heltvily on the needs of the user. The selection strategy we present involves weighting possible strategic predicates and the propositimm used to fill them at mnltlple points throughout an ongoing dislogue and at the actual time of giving the definition. Weighting will be influenced by a model of the user&apos;s domain kimwl- edge, taskqelated plans and goals, and receptivity to the different kinds of intormation that could be presented. An utterance ca then be produced that incorporates the most important information while adheriog to common rhetorical practices

(Semi-)Closed Loop Recycling of Solid Oxide Cells

Fuel cell and hydrogen applications will be key to enable the transition towards decarbonization and achieving the EU's targets of zero net greenhouse gas emissions by 2050. In the next years, priority will be set on the expansion of suitable hydrogen electrolyzers, such as solid oxide electrolysis cells (SOECs). Compared to other types of electrolyzers, the SOEC has a moderate technology readiness level (TRL 5-7). In order to facilitate the market entry and at the same time recover valuable raw materials, recycling concepts have to be developed and implemented at an early stage.The task of reusing or recovering high-temperature electrolyzer components is being addressed and focusses on the reprocessing of ceramic components of End-of-Life SOECs. Recycling in a closed-loop is particularly desirable, while the process is designed to be as scalable as possible. The biggest challenge for SOC recycling arises from the fact that no standardized manufacturing process for hydrogen electrolysis stacks/cells is currently existing. As a result, several cell types are available, sometimes differing significantly in their structures, materials and materials shares used. The cell designs can be divided into metal-supported cells (MSCs), electrolyte-supported cells (ESCs), and fuel electrode-supported cells (FESCs). Even within one cell type, differences can occur depending on the manufacturer. Therefore, it is likely that a classification and separation according to comparable cell types will be needed in the future.We focus mainly on the recycling of FESC-type cells. After separation from the stack, the cell will undergo different stages within the recycling process, illustrated in Figure 1. After re-oxidizing the whole cell, the air electrode and contact layer (~15 wt%) are removed by acid treatment, however most parts of the cell remain stable (~85 wt%). This solid fraction is further milled down and reprocessed to substrate slurry. Defined portions of the recycled slurry are admixed with standard slurry. The resulting green tapes and sintered bodies are investigated in terms of microstructure and mechanical stability.Parts of the liquid fraction of the cell, according to ~15 wt% of the cell, are recovered by oxalate precipitation of lanthanum. It was possible to recover ~95% of the lanthanum contained, which corresponds to about 60 wt% of the total dissolved load

Recycling Strategies for Solid Oxide Cells

Alongside the generation of renewable power and its storage in batteries, hydrogen technologies are essential to enable a deep decarbonization of the energy system. These technologies include solid oxide cells (SOCs), which can be operated as electrolyzers to generate hydrogen or syngas and/or for power supply in fuel cell mode and demonstrate the highest electrical efficiency among electrochemical converters. However, SOCs like other energy technologies contain significant amounts of critical raw materials, which should be preserved appropriately. Therefore, the development of economically viable recycling strategies is required even at an early market entry stage. In this paper, potential recycling routes for SOC stack components are discussed. Based on state-of-the-art materials and cell designs, the future challenges related to SOC recycling are outlined, and possible recycling pathways for all SOC components are presented with an emphasis on the ceramic fractions. Their economic and environmental potentials are evaluated, showing the significant advantages offered by recycling