Who is accessing public-sector anti-retroviral treatment in the Free State, South Africa? An exploratory study of the first three years of programme implementation

<p>Abstract</p> <p>Background</p> <p>Although South Africa has the largest public-sector anti-retroviral treatment (ART) programme in the world, anti-retroviral coverage in adults was only 40.2% in 2008. However, longitudinal studies of who is accessing the South African public-sector ART programme are scarce. This study therefore had one main research question: who is accessing public-sector ART in the Free State Province, South Africa? The study aimed to extend the current literature by investigating, in a quantitative manner and using a longitudinal study design, the participants enrolled in the public-sector ART programme in the period 2004-2006 in the Free State Province of South Africa.</p> <p>Methods</p> <p>Differences in the demographic (age, sex, population group and marital status) socio-economic (education, income, neo-material indicators), geographic (travel costs, relocation for ART), and medical characteristics (CD4, viral load, time since first diagnosis, treatment status) among 912 patients enrolled in the Free State public-sector ART programme between 2004 and 2006 were assessed with one-way analysis of variance, Bonferroni post-hoc analysis, and cross tabulations with the chi square test.</p> <p>Results</p> <p>The patients accessing treatment tended to be female (71.1%) and unemployed (83.4%). However, although relatively poor, those most likely to access ART services were not the most impoverished patients. The proportion of female patients increased (<it>P </it>< 0.05) and their socio-economic situation improved between 2004 and 2006 (<it>P </it>< 0.05). The increasing mean transport cost (<it>P </it>< 0.05) to visit the facility is worrying, because this cost is an important barrier to ART uptake and adherence. Encouragingly, the study results revealed that the interval between the first HIV-positive diagnosis and ART initiation decreased steadily over time (<it>P </it>< 0.05). This was also reflected in the increasing baseline CD4 cell count at ART initiation (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>Our analysis showed significant changes in the demographic, socio-economic, geographic, and medical characteristics of the patients during the first three years of the programme. Knowledge of the characteristics of these patients can assist policy makers in developing measures to retain them in care. The information reported here can also be usefully applied to target patient groups that are currently not reached in the implementation of the ART programme.</p

Extra-pair parentage and personality in a cooperatively breeding bird

Why so much variation in extra-pair parentage occurs within and among populations remains unclear. Often the fitness costs and benefits of extra-pair parentage are hypothesised to explain its occurrence; therefore, linking extra-pair parentage with traits such as personality (behavioural traits that can be heritable and affect reproductive behaviour) may help our understanding. Here, we investigate whether reproductive outcomes and success are associated with exploratory behaviour in a natural population of cooperatively breeding Seychelles warblers (Acrocephalus sechellensis) on Cousin Island. Exploratory behaviour correlates positively with traits such as risk-taking behaviour and activity in other wild bird species and might promote extra-pair mating by increasing the rate at which potential extra-pair partners are encountered. We therefore predicted that fast-exploring individuals would have more extra-pair offspring. There is also a potential trade-off between pursuing extra-pair parentage and mate guarding in males. We therefore also predicted that fast-exploring males would be more likely to pursue extra-pair parentage and that this would increase the propensity of their mate to gain extra-pair parentage. We found that neither the total number of offspring nor the number of extra-pair offspring were associated with a male’s or female’s exploratory behaviour. However, there was a small but significant propensity for females to have extra-pair fertilisations in pairs that were behaviourally disassortative. Overall, we conclude that, due to the small effect size, the association between exploratory behaviour and extra-pair paternity is unlikely to be biologically relevant. Significance statement: True genetic monogamy is rare, even in socially monogamous systems, and multiple factors, such as behaviour, social structure, morphology and physiology, determined by the biological system can cause variation in extra-pair parentage (EPP). Therefore, investigating the inherent differences in these factors among individuals could be informative. We investigated whether reproductive outcomes/success are associated with differences in the propensity to explore novel environments/objects in a promiscuous, island-dwelling cooperatively breeding bird, the Seychelles warbler. Our results showed that exploratory behaviour was not associated with the number of offspring produced by an individual, and thus the long-term fitness consequences of different exploratory tendencies did not differ. We also found that the propensity to engage in EPP in females was higher in dissimilar behavioural pairs, but due to the small effect size, we hesitate to conclude that there are personality-dependent mating outcomes in the population

Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.

BACKGROUND: Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand. METHODS AND FINDINGS: The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3)) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p=0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported. CONCLUSIONS: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary

Protocol for Simulations of PEGylated Proteins with Martini 3

Enhancement of proteins by PEGylation is an active area of research. However, the interactions between polymer and protein are far from fully understood. To gain a better insight into these interactions or even make predictions, molecular dynamics (MD) simulations can be applied to study specific protein-polymer systems at molecular level detail. Here we present instructions on how to simulate PEGylated proteins using the latest iteration of the Martini coarse-grained (CG) force-field. CG MD simulations offer near atomistic information and at the same time allow to study complex biological systems over longer time and length scales than fully atomistic-level simulations.</p