Shifting to tenofovir use in first-line antiretroviral therapy for HIV-positive adults in public sector treatment programs in sub-Saharan Africa

The success of scale up of antiretroviral therapy (ART) in low- and middle-income countries (LMICs) is in large part due to the introduction of a “public health approach” to access advocated by the World Health Organization (WHO) which emphasized standardized treatment regimens that could be purchased in large quantities and delivered at scale. In 2010 the WHO updated their global HIV treatment guidelines recommending the substitution of stavudine with tenofovir (both of which are members of the non-nucleoside reverse transcriptase inhibitor (NRTI) class of drugs) in first-line antiretroviral therapy (ART). Given the size of treatment programs in sub-Saharan Africa, changing the NRTI used in first-line therapy for HIV could have a substantial impact on treatment outcomes. We conducted three prospective cohort studies using clinical datasets from several sub-Saharan African countries to answer questions surrounding the impacts of exposure to tenofovir in first-line therapy. The first study examines the frequency of stavudine use and single-drug substitutions (substituting the NRTI in first-line ART) in three regions in sub-Saharan Africa by calendar year, 2004–2014. We found a total of 33,441 (8.9%; 95% CI: 8.7–8.9%) single-drug substitutions occurred among 377,656 patients in the first 24 months on ART, close to 40% of which were amongst patients on stavudine. The decrease in single-drug substitutions corresponded with the phasing out of stavudine. We saw an 80% reduction in the risk of single-drug substitutions when comparing tenofovir to stavudine and close to a 70% reduction in the risk when comparing zidovudine to stavudine. The second study uses a regression discontinuity design to evaluate the impact of national HIV treatment guideline changes in South Africa and Zambia recommending tenofovir in first-line ART on treatment outcomes. We found that updated WHO guidelines increased the proportion of patients initiating tenofovir (risk difference (RD) (South Africa): 81%; 95% CI: 73%, 89%; RD (Zambia): 42%; 95% CI: 38%, 45%). Intent to treat estimates showed a decrease in single-drug substitutions in South Africa (RD: -15%; 95% CI: -18%, -12%) and Zambia (RD: -2.0%; 95% CI: -3.6%, -0.3%). In both countries, there was no effect on mortality, attrition or viral load failure (South Africa only). The third study investigates the effect of the 2012 tenofovir stock shortage in South Africa on provider and patient level outcomes, using data from four public-sector Right to Care clinics, two of which experienced a tenofovir stock shortage and two that did not. While imprecise, our results suggest a potential shift in how providers managed patients during the period of the shortage, mainly, a noticeable decrease in the average number of days between visits during the shortage compare to before or after at all four clinics and a significant difference in the proportion of patients missing visits. Difference-in-difference regression results showed a small, but significant, increase in the risk of missed visits during the shortage compared to after (RD: 1.2%; 95% CI: 0.5%, 2.0%), mainly driven by ACTs clinic. No significant difference was seen in other outcomes. Great strides have been made to extend access to ART as well as increase the quality of the services provided to patients in sub-Saharan Africa. Continued access to and a consistent supply of tenofovir in this setting is necessary for patients to receive drugs that are comparable to those used for HIV treatment in high-income countries, as we show that phasing out of stavudine and for either zidovudine or tenofovir potentially reduced toxicities and potentially improved quality of life in multiple regions throughout sub-Saharan Africa. While we show little effect on treatment outcomes when comparing patients accessing care and treatment during the shortage of tenofovir compared to those that did not, this most likely reflects the clinics’ ability to offset the crisis by continuing to initiate newly diagnosed and eligible patients on treatment and keep treatment experienced patients on their current regimen

Watching nightlife: affective labor, social media and surveillance

This article examines the affective labor of nightlife photographers within the surveillance economy of social media. I examine nightlife photographers as “below the line” cultural laborers who employ their identities and communicative capacities to create and circulate images of nightlife online. These images stimulate interaction that can be watched, tracked, and responded to by the databases of social media. The study draws on interviews with nightlife photographers to examine how they account for the creative and promotional aspects of their labor. I argue that the analytical capacities of social media databases, and the modes of promotion they facilitate, depend in the first instance on the affective labor of cultural intermediaries like nightlife photographers

Introduction: Risking Feeling: Alice Munro’s Fiction of “Exquisite Shame”

This introduction places the volume in the context of previous scholarship on Munro and anchors the collection in the wealth of affect and ethical theory that has informed recent cultural studies. We argue that these new essays, taken together, offer us an Alice Munro who is not the kindly Canadian icon reinforcing small-town verities who was celebrated and perpetuated in acts of national teaching with her Nobel Prize win; they ponder, instead, an edgier, messier Munro whose fictions of affective and ethical perplexities disturb rather than comfort

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

Revisiting task orientated care: Oral histories of former student nurses in Ireland (1960–2001)

The apprenticeship model of nurse training was in place in Ireland up to the end of the twentieth century. Task orientated care was a feature of this model. It is important to examine task allocation from the student's perspective, in light of current and on-going debates regarding student nurses' supernumerary status. Both approaches influence the status of the student; worker with task allocation and learner with supernumerary status. Oral history interviews were undertaken with twelve former student nurses (1960–2001) to explore their experiences of clinical learning and task allocation. Task allocation consisted of household tasks and tasks involving patient care. Students' experiences were influenced more by issues surrounding the task, particularly the 'task-person', than the task itself. Therefore, a learning environment that is inclusive, supportive and understanding of students' learning is recommended, regardless of the model of nurse training or education that might be in place. These findings can inform current debate on supernumerary status and task allocation for the student nurse within their clinical learning environment, but also on the history of nurse education in Ireland in the twentieth century