Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens

Background The accumulation of mutations after long-lasting exposure to a failing combination antiretroviral therapy (cART) is problematic and severely reduces the options for further successful treatments. Methods We studied patients from the Swiss HIV Cohort Study who failed cART with nucleoside reverse transcriptase inhibitors (NRTIs) and either a ritonavir-boosted PI (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The loss of genotypic activity <3, 3–6, >6 months after virological failure was analyzed with Stanford algorithm. Risk factors associated with early emergence of drug resistance mutations (<6 months after failure) were identified with multivariable logistic regression. Results Ninety-nine genotypic resistance tests from PI/r-treated and 129 from NNRTI-treated patients were analyzed. The risk of losing the activity of ≥1 NRTIs was lower among PI/r- compared to NNRTI-treated individuals <3, 3–6, and >6 months after failure: 8.8% vs. 38.2% (p = 0.009), 7.1% vs. 46.9% (p<0.001) and 18.9% vs. 60.9% (p<0.001). The percentages of patients who have lost PI/r activity were 2.9%, 3.6% and 5.4% <3, 3–6, >6 months after failure compared to 41.2%, 49.0% and 63.0% of those who have lost NNRTI activity (all p<0.001). The risk to accumulate an early NRTI mutation was strongly associated with NNRTI-containing cART (adjusted odds ratio: 13.3 (95% CI: 4.1–42.8), p<0.001). Conclusions The loss of activity of PIs and NRTIs was low among patients treated with PI/r, even after long-lasting exposure to a failing cART. Thus, more options remain for second-line therapy. This finding is potentially of high relevance, in particular for settings with poor or lacking virological monitoring.

Behind the curtains of privacy calculus on social networking sites: the study of Germany and the USA

As social networking sites (SNSs) become increasingly global, the issues of cultural differences in participation patterns become acute. However, current research offers only limited insights into the role of culture behind SNS usage. Aiming to fill this gap, this study adopts a ‘privacy calculus’ perspective to study the differences between German and American SNS users. Results of structural equation modeling and multi-group analysis reveal distinct variability in the cognitive patterns of American and German subjects. We contribute to the theory by rejecting the universal nature of privacy-calculus processes. From a practical standpoint, our results signal that SNS providers cannot rely on the “proven” means in ensuring user participation when crossing geographic boundaries. When financial means are limited, SNS providers should direct their investments into enhancing platform enjoyment and granting users with more control and, paradoxically, lobbying for more legalistic safeguards of user privacy.

Investigating the value of privacy on online social networks: conjoint analysis

Popularity of Online Social Networks has been recently overshadowed by the privacy problems they pose. Users are getting increasingly vigilant concerning information they disclose and are strongly opposing the use of their information for commercial purposes. Nevertheless, as long as the network is offered to users for free, providers have little choice but to generate revenue through personalized advertising to remain financially viable. Our study empirically investigates the ways out of this deadlock. Using conjoint analysis we find that privacy is indeed important for users. We identify three groups of users with different utility patterns: Unconcerned Socializers, Control-conscious Socializers and Privacy-concerned. Our results provide relevant insights into how network providers can capitalize on different user preferences by specifically addressing the needs of distinct groups in the form of various premium accounts. Overall, our study is the first attempt to assess the value of privacy in monetary terms in this context.

Book Review: Protection of Cultural Diversity from a European and International Perspective

A review of the volume of collected essays edited by Hildegard Schneider and Peter van den Bossche (Intersentia 2008), which looks at diverse implications of the recently adopted UNESCO Convention on Cultural Diversity and discusses these from European and international law perspectives.

Vesicular stomatitis virus replicon expressing the VP2 outer capsid protein of bluetongue virus serotype 8 induces complete protection of sheep against challenge infection.

Bluetongue virus (BTV) is an arthropod-borne pathogen that causes an often fatal, hemorrhagic disease in ruminants. Different BTV serotypes occur throughout many temperate and tropical regions of the world. In 2006, BTV serotype 8 (BTV-8) emerged in Central and Northern Europe for the first time. Although this outbreak was eventually controlled using inactivated virus vaccines, the epidemic caused significant economic losses not only from the disease in livestock but also from trade restrictions. To date, BTV vaccines that allow simple serological discrimination of infected and vaccinated animals (DIVA) have not been approved for use in livestock. In this study, we generated recombinant RNA replicon particles based on single-cycle vesicular stomatitis virus (VSV) vectors. Immunization of sheep with infectious VSV replicon particles expressing the outer capsid VP2 protein of BTV-8 resulted in induction of BTV-8 serotype-specific neutralizing antibodies. After challenge with a virulent BTV-8 strain, the vaccinated animals neither developed signs of disease nor showed viremia. In contrast, immunization of sheep with recombinant VP5 - the second outer capsid protein of BTV - did not confer protection. Discrimination of infected from vaccinated animals was readily achieved using an ELISA for detection of antibodies against the VP7 antigen. These data indicate that VSV replicon particles potentially represent a safe and efficacious vaccine platform with which to control future outbreaks by BTV-8 or other serotypes, especially in previously non-endemic regions where discrimination between vaccinated and infected animals is crucial.