Starting infants on antiretroviral therapy

The most effective way to combat paediatric HIV infection is through good management of maternal health and prevention of mother-to-child transmission (PMTCT). However, by the end of 2007, of an estimated 33.2 million people living with HIV, 2.1 million were children. Of these 90% lived in sub-Saharan Africa and 420 000 were newly infected in that year.1 Although in recent years the number of children treated with antiretroviral therapy (ART) has increased from about 75 000 in 2005 to almost 200 000 in 2007, many children living with HIV are not receiving treatment. Without it approximately 35% will die before their first birthday and 53% by the time they reach the age of 2 years.2 By age 5 years it is estimated that 62 - 89% of children will have died.3,4 Emerging data from sub-Saharan Africa show that most children starting ART are doing so at older ages, usually 5 years or more, that most start at a late stage of the disease, and that mortality in the first few months of treatment remains high.5,6 A recent study shows that starting treatment in early infancy can be lifesaving, and this has informed revisions in World Health Organization (WHO) guidelines7,8 (see WHO ‘Dear Health Care Provider' letter, Fig. 1). At present the majority of children who could benefit from these recommendations are not being diagnosed or treated. Southern African Journal of HIV Medicine Vol. 9 (4) 2008: pp. 25-3

Safety and pharmacokinetics of dolutegravir in HIV-positive pregnant women: a systematic review

Background: The integrase strand transfer inhibitor dolutegravir (DTG) is being introduced into low- and middle-income countries (LMICs) as an alternative to first-line treatment with non-nucleoside reverse transcriptase inhibitors. However, DTG is not yet widely recommended for use in pregnant women. The aim of this systematic review was to analyse all available data on birth outcomes and congenital anomalies in the infants of pregnant women treated with DTG. Methods: A PubMed and Embase search was conducted using the terms "dolutegravir" or "DTG" and "pregnancy" or "pregnant" from the earliest available date on the database to 26 July 2017. Any reports involving women who were pregnant, HIV positive and taking DTG were included. The percentage of pregnant women with adverse birth outcomes or congenital anomalies in their infants after taking dolutegravir was compared with five historical control databases. Results: There were six databases included in the main analysis of birth outcomes and congenital anomalies, with a total of 1200 pregnant women. The percentage of pregnant women taking DTG with adverse birth outcomes and congenital abnormalities was similar to results from historical control studies of HIV-positive women. However, there was significant heterogeneity among the six databases - the percentage of infants with congenital anomalies ranged from 0.0% in Botswana (0/116 infants) to 13.3% in IMPAACT P1026S (2/15 infants). Conclusions: Up to 15 million people could be on treatment with DTG in LMICs within the next 5 years, of whom a substantial percentage is likely to be women of child-bearing potential. In many countries with large HIV epidemics, unplanned pregnancies are common and access to antenatal clinic facilities may be limited. Continued pharmacovigilance is essential, but it is reassuring that no clear safety signals have been detected, to date, for pregnant women treated with DTG in terms of birth outcomes or congenital anomalies

Efavirenz in pregnancy

Clinical guidelines from the National Department of Health (DoH), South Africa, for prevention of mother-tochild transmission (PMTCT), revised in 2010, recommend that HIV-positive pregnant women with a CD4 count of 350 cells/μl or less commence lifelong antiretroviral therapy (ART).¹ DoH guidance for women initiating ART in pregnancy in the public sector – on which the overwhelming majority of HIV-positive South Africans rely for their care – recommends they receive nevirapine with tenofovir and lamivudine or emtricitabine at any stage of gestation. In cases where a woman is already receiving ART with an efavirenz-based regimen, it is recommended that this should be substituted for nevirapine if she is still in the first trimester of pregnancy. Efavirenz is therefore contraindicated in pregnant women at any time during pregnancy; for those already receiving the drug, it is only switched in the first trimester. The concern about the use of efavirenz in pregnancy dates back to preclinical studies. It is the only antiretroviral with preclinical primate data and in turn has the strongest US Food and Drug Administration (FDA) category and the most scrutiny during pregnancy.² The drug also has the most conflicting recommendations, both from guidelines and product labelling. This article is a summary of what we know (and do not know) about using efavirenz in pregnancy. We argue that reconsideration of the risk and benefits of this evidence, which has informed South African guidance, is warranted

Influence of the Nb/P ratio of acidic Nb-P-Si oxides on surface and catalytic properties

In this work, two acidic Nb-P-Si mixed oxide gel-derived materials characterized by Nb/P molar ratios equal to 2 (5Nb2.5 P) and 1 (2.5NbP) were investigated for their surface and bulk properties in relation with the catalytic performances in the fructose dehydration reaction. The structural characteristics of the studied samples and the changes occurring after water treatment and after reaction were investigated by 29Si and 31P solid state nuclear magnetic resonance (MAS-NMR) and X-ray photoelectron (XPS) spectroscopies, while the characterization of their acidic properties was performed by base (2-phenylethylamine) adsorption in liquid phase. MAS-NMR showed that the phosphorus remains firmly anchored into the siloxane matrix after exposure to cold water for 5Nb2.5 P sample and XPS confirmed the homogeneity of the sample composition. Both samples exhibited good intrinsic acidity and maintained significant effective acidity in polar-protic liquids; 2.5NbP manifested a double amount of acid sites compared to 5Nb2.5 P, when 2-phenylethylamine is used as probe. Fructose dehydration to 5-(hydroxymethyl)furfural (HMF) on the two gel-derived catalysts was performed in water and in water-isopropanol solution under mild conditions (130 °C) working in a recirculation reaction line comprising a tubular catalytic reactor. In water-isopropanol solution, the samples displayed good performances, as expected thanks to the lively effective acidity. Around 45-50% fructose conversion was attained on both samples, with selectivity to HMF equal to about 50% on 2.5NbP gel-derived catalyst. Recycling tests showed satisfactorily stable activity during three consecutive runs

Temporalities of Transience and the Mortuary Landscape: The Example of Natural Burial

'Passing' is a common euphemism for the death of a person, as he or she is said to 'pass away' or 'pass on'. This open-ended saying has at its heart a notion of transformation from one state to another, which in turn grants the possibility of grasping or approximating the passage of time and the materiality of death and decay. This book begins with the idea that since all material things - whether animals, human-beings, objects or buildings - undergo some form of passing, then the specific transformation in these passages and the materiality actively given to it can offer us a grasp of otherwise precarious temporalities. It examines how human beings strive to relate to the temporal dimension of death and decay, by giving new shape and direction to being and by examining its natural transformations. Focusing on the materiality of passing, and thereby the relationship between embodiment, temporality and death, Materialities of Passing offers rich case studies from Europe, Papua New Guinea, South Africa and the Russian Far East to exploring the material, spatial and directional aspects of the very interface between life and death. As such, it will appeal to scholars of anthropology, death studies, archaeology, philosophy and cultural studies

A molecular communication channel consisting of a single reversible chain of hydrogen bonds in a conformationally flexible oligomer

Communication of information through the global switching of conformation in synthetic molecules has hitherto entailed the inversion of chirality. Here, we report a class of oligomer through which information may be communicated through a global reversal of polarity. Ethylene-bridged oligoureas are constitutionally symmetrical, conformationally flexible molecules organized by a single chain of hydrogen bonds running the full length of the oligomer. NMR reveals that this hydrogen-bonded chain may undergo a coherent reversal of directionality. The directional uniformity of the hydrogen-bond chain allows it to act as a channel for the spatial communication of information on a molecular scale. A binding site at the terminus of an oligomer detects local information about changes in pH or anion concentration and transmits that information—in the form of a directionality switch in the hydrogen-bond chain—to a remote polarity-sensitive fluorophore. This propagation of polarity-encoded information provides a new mechanism for molecular communication

Reverse Biomimetic’ Synthesis of L-Arogenate and its Stabilized Analogues from L-Tyrosine

l-Arogenate (also known as l-pretyrosine) is a primary metabolite on a branch of the shikimate biosynthetic pathway to aromatic amino acids. It plays a key role in the synthesis of plant secondary metabolites including alkaloids and the phenylpropanoids that are the key to carbon fixation. Yet understanding the control of arogenate metabolism has been hampered by its extreme instability and the lack of a versatile synthetic route to arogenate and its analogues. We now report a practical synthesis of l-arogenate in seven steps from O-benzyl l-tyrosine methyl ester in an overall yield of 20%. The synthetic route also delivers the fungal metabolite spiroarogenate, as well as a range of stable saturated and substituted analogues of arogenate. The key step in the synthesis is a carboxylative dearomatization by intramolecular electrophilic capture of tyrosine's phenolic ring using an N-chloroformylimidazolidinone moiety, generating a versatile, functionalizable spirodienone intermediate

A Robust Cross-Linking Strategy for Block Copolymer Worms Prepared via Polymerization-Induced Self-Assembly

A poly(glycerol monomethacrylate) (PGMA) chain transfer agent is chain-extended by reversible addition-fragmentation chain transfer (RAFT) statistical copolymerization of 2-hydroxypropyl methacrylate (HPMA) with glycidyl methacrylate (GlyMA) in concentrated aqueous solution via polymerization-induced self-assembly (PISA). A series of five free-standing worm gels is prepared by fixing the overall degree of polymerization of the core-forming block at 144 while varying its GlyMA content from 0 to 20 mol %. 1H NMR kinetics indicated that GlyMA is consumed much faster than HPMA, producing a GlyMA-rich sequence close to the PGMA stabilizer block. Temperature-dependent oscillatory rheological studies indicate that increasing the GlyMA content leads to progressively less thermoresponsive worm gels, with no degelation on cooling being observed for worms containing 20 mol % GlyMA. The epoxy groups in the GlyMA residues can be ring-opened using 3-aminopropyltriethoxysilane (APTES) in order to prepare core cross-linked worms via hydrolysis-condensation with the siloxane groups and/or hydroxyl groups on the HPMA residues. Perhaps surprisingly, 1H NMR analysis indicates that the epoxy-amine reaction and the intermolecular cross-linking occur on similar time scales. Cross-linking leads to stiffer worm gels that do not undergo degelation upon cooling. Dynamic light scattering studies and TEM analyses conducted on linear worms exposed to either methanol (a good solvent for both blocks) or anionic surfactant result in immediate worm dissociation. In contrast, cross-linked worms remain intact under such conditions, provided that the worm cores comprise at least 10 mol % GlyMA

Synthesis of a mitochondria-targeted spin trap using a novel Parham-type cyclization

A new cyclic nitrone spin trap, [4-(3′,3′-dibutyl-2′-oxy-3′H-isoindol-5′-yloxy)butyl]triphenylphosphonium bromide (MitoSpin), bearing a lipophilic cation has been prepared by a route that involves a novel Parham-type lithiation–cyclization of an isocyanate to give the isoindolinone core. MitoSpin accumulates in a membrane potential dependent way in energized mitochondria and its oxidation could potentially be used in the study of oxidative stress resulting from reactive oxygen species generated in mitochondria