Uptake of Home-Based HIV Testing,Linkage to Care,and Community Attitudes about ART in Rural KwaZulu-Natal,South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial

BackgroundThe 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART.ConclusionsHome-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01509508","term_id":"NCT01509508"}}NCT01509508     

Computational identification and comparative analysis of miRNA precursors in three palm species

Planta - In the present study, miRNA precursors in the genomes of three palm species were identified. Analyzes of sequence conservation and biological function of their putative targets contribute...     

Universal definition of loss to follow-up in HIV treatment programs: a statistical analysis of 111 facilities in Africa, Asia, and Latin America

Background

Although patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition.

Methods and Findings

At a set “status classification” date, patients were categorized as either “active” or “LTFU” according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities—representing 180,718 patients from 19 countries—were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173–181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%–7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean = 150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean = 1.2%, 95% CI: 1.0%–1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean = 19.9%, 95% CI: 19.1%–21.7%).

Conclusions

Based on this evaluation, we recommend the adoption of ≥180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide. Please see later in the article for the Editors'' Summary     

Phylogenetic relationships within the Laridae (Charadriiformes: Aves) inferred from mitochondrial markers

Gulls (Aves: Laridae) constitute a recent and cosmopolite family of well-studied seabirds for which a robust phylogeny is needed to perform comparative and biogeographical analyses. The present study, the first molecular phylogeny of all Larids species (N=53), is based on a combined segment of mtDNA (partial cytochrome b and control region). We discuss our phylogenetic tree in the light of previous suggestions based on morphological, behavioral, and plumage characters. Although the phylogeny is not fully resolved, it highlights several robust species groups and confirms or identifies for the first time some sister relationships that had never been suggested before. The Dolphin Gull (Leucophaeus scoresbii) for instance, is identified as the sister species of the Grey Gull (Larus modestus) and the Ross's Gull (Rhodostethia rosea) forms a monophyletic group with the Little Gull (Larus minutus). Our results clearly demonstrate that the genus Larus as currently defined is not monophyletic, since current taxonomy of gulls is based on the use of convergent phenotypic characters. We propose a new systematic arrangement that better reflects their evolutionary history.     

Two-dimensional gel electrophoresis based technologies for potential biomarkers identification in amniotic fluid: a simple model

To assess the efficiency of two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and of two-dimensional electrophoresis and ammoniacal silver staining (2D-E), different amounts of soybean trypsin inhibitor and horse myoglobin were added to amniotic fluid. In this model, a minimum of 5 to 10 ng of "artificial" biomarkers was detected.     

Occurrence of Listeria spp. in Effluents of French Urban Wastewater Treatment Plants

Listeria spp. were found in most treated waters (84.4%) and raw sludge (89.2%) of six French urban wastewater treatment plants and one composting facility, examined monthly over a 1-year period. Most strains belonged to Listeria monocytogenes, serotypes 4b/4e being predominant. Sludge composting and liming reduced or prevented Listeria contamination.     

Effect of over-expression of neuropathy target esterase on mammalian cell proliferation

Neuropathy target esterase (NTE), the human homologue of a protein required for brain development in Drosophila, is expressed primarily in neural cells but is also detected in non-neural cells. Although NTE has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation, the function of NTE has not been defined in neural cells. In this study we have investigated the possible role of NTE in neuroblastoma cells and non-neural cells using an over-expression strategy. Over-expression of NTE in human neuroblastoma SH-SY5Y cells and monkey kidney COS7 cells led to an accumulation of NTE on the cytoplasmic surface of the endoplasmic reticulum and inhibition of cell proliferation. In particular, high levels of NTE arrested COS7 cells at G2/M stage yet was not associated with arrest at a particular phase of the cell cycle in SH-SY5Y cells. Moreover, over-expression of NTE did not induce apoptosis in two kinds of cell lines as assessed by flow cytometry. These results suggest that the role of NTE over-expression in cell proliferation is associated with different mechanisms in different cells.     

Ligand Binding and Crystal Structures of the Substrate-Binding Domain of the ABC Transporter OpuA

Background

The ABC transporter OpuA from Lactococcus lactis transports glycine betaine upon activation by threshold values of ionic strength. In this study, the ligand binding characteristics of purified OpuA in a detergent-solubilized state and of its substrate-binding domain produced as soluble protein (OpuAC) was characterized.

Principal Findings

The binding of glycine betaine to purified OpuA and OpuAC (K_D = 4–6 µM) did not show any salt dependence or cooperative effects, in contrast to the transport activity. OpuAC is highly specific for glycine betaine and the related proline betaine. Other compatible solutes like proline and carnitine bound with affinities that were 3 to 4 orders of magnitude lower. The low affinity substrates were not noticeably transported by membrane-reconstituted OpuA. OpuAC was crystallized in an open (1.9 Å) and closed-liganded (2.3 Å) conformation. The binding pocket is formed by three tryptophans (Trp-prism) coordinating the quaternary ammonium group of glycine betaine in the closed-liganded structure. Even though the binding site of OpuAC is identical to that of its B. subtilis homolog, the affinity for glycine betaine is 4-fold higher.

Conclusions

Ionic strength did not affect substrate binding to OpuA, indicating that regulation of transport is not at the level of substrate binding, but rather at the level of translocation. The overlap between the crystal structures of OpuAC from L.lactis and B.subtilis, comprising the classical Trp-prism, show that the differences observed in the binding affinities originate from outside of the ligand binding site.     

Importance of a hydrophobic pocket for peptide binding in lactococcal OppA

Lactococcal oligopeptide-binding protein A (OppA) binds peptides with widely varied lengths and sequences. We previously hypothesized that a hydrophobic pocket in OppA preferentially binds a hydrophobic peptide side chain and thus determines its binding register. Two crystal structures of OppA with different nonapeptides now indeed show binding in different registers.