Monitoring and evaluation of sport-based HIV/AIDS awareness programmes: strengthening outcome indicators

There are number of Non-Governmental Organisations (NGOs) in South Africa that use sport as a tool to respond to Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS), however, little is reported about the outcomes and impact of these programmes. The aim of this study is to contribute to a generic monitoring and evaluation framework by improving the options for the use of outcome indicators of sport-based HIV/AIDS awareness programmes of selected NGOs in South Africa. A qualitative method study was carried out with seven employees of five selected NGOs that integrate sport to deliver HIV/AIDS programmes in South Africa. The study further involved six specialists/experts involved in the field of HIV/ AIDS and an official from Sport Recreation South Africa (SRSA). Multiple data collection instruments including desktop review, narrative systematic review, document analysis, one-on-one interviews and focus group interview were used to collect information on outcomes and indicators for sport-based HIV/AIDS awareness programmes. The information was classified according to the determinants of HIV/AIDS. The overall findings revealed that the sport-based HIV/AIDS awareness programmes of five selected NGOs examined in this study focus on similar HIV prevention messages within the key priorities highlighted in the current National Strategic Plan for HIV/AIDS, STIs and TB of South Africa. However, monitoring and evaluating outcomes of sport-based HIV/AIDS programmes of the selected NGOs remains a challenge. A need exists for the improvement of the outcome statements and indicators for their sport-based HIV/AIDS awareness programmes. This study proposed a total of 51 generic outcome indicators focusing on measuring change in the knowledge of HIV/AIDS and change in attitude and intention towards HIV risk behaviours. In addition, this study further proposed a total of eight generic outcome indicators to measure predictors of HIV risk behaviour. The selected NGOs can adapt the proposed generic outcomes and indicators based on the settings of their programmes. A collaborative approach by all stakeholders is required, from international organisations, funders, governments, NGOs and communities to strengthening monitoring and evaluation of sport-based HIV/AIDS awareness programmes including other development programmes. This will assist the NGOs that use sport for development to be able to reflect accurately the information about their HIV/AIDS activities and also be able to contribute to on-going monitoring activities at a national and global level as well as to the Sustainable Development Goals.IS

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa

All files are available from the GenBank database under accession numbers KT031999-KT032063.Ms LAW Hahne for the development of the electronic database for the Kalafong clinic. Mr T Moto for the assistance with data collection. Drs G Malherbe and P Mahasha for assisting with the development of the genotyping assay and the staff at the HIV clinics for their dedicated service to patients and their assistance with data collection.Conceived and designed the experiments: TR UF. Performed the experiments: GVD. Analyzed the data: GM. Contributed reagents/materials/analysis tools: TR GM. Wrote the paper: TR UF GM GVD WT NDP TA.OBJECTIVE Limited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors. METHODS Data from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis. RESULTS The study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;- 2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033). CONCLUSION Major protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed.This research and selected researchers (TR and GVD) were partially funded by a grant from the Delegation of the European Union to South Africa: "Drug Resistance Surveillance and Treatment Monitoring Network for the Public Sector HIV Antiretroviral Treatment Programme in the Free State” - Sante 2007/147-790 - and National Research Council of South Africa, Unlocking the Future 61509.http://www.plosone.orgam201

Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration

BACKGROUND Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration. METHODOLOGY/PRINCIPAL FINDINGS Data from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<-3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines. CONCLUSIONS/SIGNIFICANCE Between 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children

Energetics and Dynamics of the Low-Lying Electronic States of Constrained Polyenes: Implications for Infinite Polyenes

Steady-state and ultrafast transient absorption spectra were obtained for a series of conformationally constrained, isomerically pure polyenes with 5–23 conjugated double bonds (N). These data and fluorescence spectra of the shorter polyenes reveal the N dependence of the energies of six [superscript 1]B[subscript u] [superscript +] and two [superscript 1]A[subscript g] [superscript –] excited states. The [superscript 1]B[subscript u] [superscript +] states converge to a common infinite polyene limit of 15 900 ± 100 cm [superscript –1]. The two excited [superscript 1]A[subscript g] [superscript –] states, however, exhibit a large (∼9000 cm–1) energy difference in the infinite polyene limit, in contrast to the common value previously predicted by theory. EOM-CCSD ab initio and MNDO-PSDCI semiempirical MO theories account for the experimental transition energies and intensities. The complex, multistep dynamics of the 1[superscript 1]B[subscript u] [superscript +] → 2 [superscript 1]A[subscript g] [superscript –] → 1 [superscript 1]A[subscript g] [superscript –] excited state decay pathways as a function of N are compared with kinetic data from several natural and synthetic carotenoids. Distinctive transient absorption signals in the visible region, previously identified with S* states in carotenoids, also are observed for the longer polyenes. Analysis of the lifetimes of the 2 [superscript 1]A[subscript g] [superscript –] states, using the energy gap law for nonradiative decay, reveals remarkable similarities in the N dependence of the 2 [superscript 1]A[subscript g] [superscript –] decay kinetics of the carotenoid and polyene systems. These findings are important for understanding the mechanisms by which carotenoids carry out their roles as light-harvesting molecules and photoprotective agents in biological systems.United States. Dept. of Energy (DE-FG02-86ER13564)National Science Foundation (U.S.) (Grant EMT-0829916)National Institutes of Health (U.S.) (Grant GM-34548

DNA damage Mechanisms and principles of homology search during recombination

Homologous recombination is crucial for genome stability and for genetic exchange. Although our knowledge of the principle steps in recombination and its machinery is well advanced, homology search, the critical step of exploring the genome for homologous sequences to enable recombination, has remained mostly enigmatic. However, recent methodological advances have provided considerable new insights into this fundamental step in recombination that can be integrated into a mechanistic model. These advances emphasize the importance of genomic proximity and nuclear organization for homology search and the critical role of homology search mediators in this process. They also aid our understanding of how homology search might lead to unwanted and potentially disease-promoting recombination events