Monitoring HIV-1 Group M in the Asia-Pacific

The Asia-Pacific is home to more than 60% of the world‘s inhabitants and the region second hardest hit by the effects of the HIV-1 pandemic, next to Sub-Saharan Africa. Many countries are low- or middle-income economies where a limited number of standardised antiretroviral therapies (ARTs) are available to treat HIV-infected patients. In resource-limited settings, viral load (VL) monitoring is not generally available to evaluate the effects of treatment. Furthermore, information is lacking as to the appropriate frequencies of VL monitoring to partner with ART. With suboptimal VL monitoring, virological breakthrough may be detected late, facilitating the accumulation of drug resistance-associated mutations (RAMs). Transmitted drug resistance would threaten already limited treatment options in the region. Viral diversity in HIV-1 epidemics is increasing. Predominant regional genotypes are subtypes B and C, CRF01_AE and their recombinants.Objectives were to contribute to efforts to monitor regional HIV-1. I evaluated impacts of diagnostic resourcing on patient treatment outcomes and provided estimates of transmitted HIV drug resistance (HIVDR). Associations between sexual exposures and HIV-1 genotype were evaluated, as were relationships between genotype and patient treatment outcomes.Analysis outcomes spanned the years 2000–2010 and included patients from Cambodia, mainland China and Hong Kong, India, Indonesia, Japan, Malaysia, Papua New Guinea, the Philippines, Singapore, South Korea, Taiwan and Thailand.Findings indicated that less-than-annual site-reported VL testing was associated with poorer treatment outcomes, including a 35% increased risk of acquired immunodeficiency syndrome (AIDS) or death. The prevalence of RAMs in our treatment-naïve patients from any drug class was 13.8%. Predominant HIV-1 genotypes were CRF01_AE and subtype B. Males and patients reporting HIV exposure as homosexual contact had a higher odds of being infected with subtype B. I found that treatment-naïve patients infected with CRF01_AE had lower changes in CD4 counts 12 months post-therapy.Results suggest the need for appropriate monitoring of VL, to improve patient treatment outcomes, and of HIVDR, to inform of risks to standardised regimen efficacy. Genotype tracking of regional variants will help to identify increasing incidence of HIV-1 genotypes in at-risk groups and contribute to monitoring HIV-1 diversity and proliferation in the region

Strengthening Innovation in the Netherlands: Making Better Use of Knowledge Creation in Innovation Activities

Strengthening the innovation system in the Netherlands is a priority for raising productivity growth, which has been relatively weak in recent years. Knowledge creation in the Netherlands is strong -- scientific publications per capita are the sixth highest in the OECD -- but innovation activity is only around the average for OECD countries according to the EIS Summary Innovation Index. The main weaknesses are in business R&D intensity, the share of the population with tertiary education, and in commercially applying new knowledge. This paper discusses reforms being implemented to overcome these weaknesses and suggests directions for building on such reforms. Co-operation between public research organisations and innovating firms is being strengthened, support for innovation is being rationalised and measures are being taken to increase both the current and prospective supply of scientists and engineers with a view to making the Netherlands a more attractive location for R&D investments. To increase the tertiary attainment rate, the authorities are considering introducing shorter tertiary courses and are experimenting with greater competition among tertiary education suppliers for public funds. To strengthen performance in commercial application of new knowledge, barriers to entrepreneurship are being reduced but more should be done to strengthen incentives for entrepreneurship. This Working Paper relates to the 2005 OECD Economic Survey of the Netherlands (www.oecd.org/eco/surveys/netherlands). Renforcer l'innovation aux Pays-Bas : Mieux utiliser la création de connaissances dans les activités d'innovation Il est essentiel de renforcer le système d’innovation aux Pays-Bas pour y relancer la croissance de la productivité, qui est relativement faible depuis quelques années. La création de connaissances est dynamique aux Pays-Bas -- qui se classe au sixième rang des pays de l’OCDE en termes de publications scientifiques par habitant -- mais les activités d’innovation se situent simplement aux alentours de la moyenne de la zone OCDE, d’après l’indice de synthèse de l’innovation (ISI) du tableau de bord européen de l’innovation (TBEI). Les principaux points faibles résident dans l’intensité de recherche-développement (R-D) des entreprises, la proportion de la population diplômée de l’enseignement supérieur, et l’exploitation commerciale des nouvelles connaissances. Ce document examine les réformes mises en ?uvre actuellement dans le but de remédier à ces faiblesses, et propose des orientations en vue d’aller plus loin. Pour l’heure, la coopération entre les organismes de recherche publics et les entreprises innovantes est renforcée, le système de soutien à l’innovation est rationalisé, et des mesures sont prises pour accroître l’offre, tant actuelle que future, de scientifiques et d’ingénieurs en vue de faire des Pays-Bas un site plus attractif pour les investissements de R-D. Afin de relever le taux de diplômés de l’enseignement supérieur, les autorités envisagent de mettre en place des formations supérieures plus courtes et ont décidé, à titre expérimental, de faire davantage jouer la concurrence entre les fournisseurs de services d’enseignement supérieur pour l’attribution des fonds publics. Afin d’améliorer les résultats obtenus en matière d’exploitation commerciale des nouvelles connaissances, les pouvoirs publics s’emploient à réduire les obstacles à l’entrepreneuriat, mais il faudrait aller plus loin pour stimuler l’esprit d’entreprise. Ce document de travail complète l’Étude économique consacrée aux Pays-Bas par l’OCDE en 2005 (www.oecd.org/eco/etudes/paysbas).regulatory reforms, product market competition, innovation, tertiary education, public research organisations, skilled migration, factor analysis, entry barriers, patents, scientists and engineers, EIS, R&D, Netherlands, intellectual property rights, tertiary attainment, taux de diplômés de l'enseignement supérieur, barrières à l'entrée, réforme de la réglementation, droit de propriété intellectuelle, enseignement supérieur, migration de travailleurs qualifiés, concurrence sur les marchés de produits, analyse factorielle, TBEI, R&D, organisme de recherche public, brevets, scientifiques et ingénieurs, innovation, Pays-Bas

Antimicrobial-Specific Cell-Mediated Immune Reconstitution in Children with Advanced Human Immunodeficiency Virus Infection Receiving Highly Active Antiretroviral Therapy

To identify virological and immunological correlates of microbial-specific immune reconstitution in children with advanced human immunodeficiency virus (HIV) infection, Candida- and tetanus-specific lymphocyte proliferation was measured in 165 children initiating a new highly active antiretroviral therapy (HAART) regimen. During the study, the proportions of children with immunity to Candida and tetanus increased from 53% to 66% and 19% to 22%, respectively. Tetanus immunity was associated with an HIV load ⩽400 RNA copies/mL and with Candida immunity. At the end of the study, 23% of the patients with baseline negative lymphocyte proliferation had tetanus immunity, and 65% had Candida immunity. Reconstitution of tetanus immunity correlated with lower end-of-study HIV loads and activated CD8+ cell percentages and higher baseline and in-study CD4+ cell percentages, but not with a gain of CD4+ cells. Reconstitution of Candida immunity showed similar trends. In conclusion, children with advanced HIV infection receiving HAART reconstituted Candida immunity more readily than they did tetanus immunity, suggesting a role for antigen reexposure. Additional factors for immune reconstitution were low HIV load, high CD4+ cell percentages, and low levels of activated CD8+ cells

Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study

BACKGROUND: Peripheral blood lymphocyte subsets need to be determined in a large, urban, minority-predominant cohort of healthy children to serve as suitable control subjects for the interpretation of the appearance of these cells in several disease conditions, notably pediatric HIV-1 infection. OBJECTIVE: We sought to determine the distribution of lymphocyte subsets in healthy urban-dwelling infants, children, and adolescents in the United States. METHODS: Lymphocyte subsets were determined by means of 3-color flow cytometry in a cross-sectional study of 807 HIV-unexposed children from birth through 18 years of age. RESULTS: Cell-surface marker analysis demonstrated that age was an extremely important variable in 24 lymphocyte subset distributions measured as percentages or absolute counts--eg, the CD4 (helper) T cell, CD8 (cytotoxic) T cell, CD19 B cell, CD4CD45RACD62L (naive helper) T cell, CD3CD4CD45RO (memory helper) T cell, CD8HLA-DRCD38 (activated cytotoxic) T cell, and CD8CD28 (activation primed cytotoxic) T cell. The testing laboratory proved to be an important variable, indicating the need for using the same laboratory or group of laboratories to assay an individual\u27s blood over time and to assay control and ill or treated populations. Sex and race-ethnicity were much less important. CONCLUSION: The results of this study provide a control population for assessment of the effects of HIV infection on the normal development and distribution of lymphocyte subsets in children of both sexes, all races, and all ethnic backgrounds from birth through 18 years of age in an urban population. This study\u27s findings will also prove invaluable in interpreting the immune changes in children with many other chronic diseases, such as primary immunodeficiency, malignancy, rheumatoid arthritis, and asthma