Kaposi sarcoma-associated herpes virus and response to antiretroviral therapy: a prospective study of HIV-infected adults

BACKGROUND The possible impact of coinfection with the Kaposi sarcoma-associated herpes virus (KSHV) on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa. METHODS We enrolled a prospective cohort of HIV-infected adults initiating ART in Johannesburg, South Africa. The subjects were defined as seropositive to KSHV if they were reactive to either KSHV lytic K8.1 or latent Orf73 antigen or to both. The subjects were followed from ART initiation until 18 months of treatment. HIV viral load and CD4 counts were tested 6 monthly. Linear generalized estimating and log-binomial regression models were used to estimate the effect of KSHV infection on immunologic recovery and response and HIV viral load suppression within 18 months after ART initiation. RESULTS Three hundred eighty-five subjects initiating ART from November 2008 to March 2009 were considered to be eligible including 184 (48%) KSHV+. The KSHV+ group was similar to the KSHV- in terms of age, gender, initiating CD4 count, body mass index, tuberculosis, and hemoglobin levels. The KSHV+ group gained a similar number of cells at 6 [difference of 10 cells per cubic millimeter, 95% confidence interval (CI): -11 to 31], 12 (3 cells per cubic millimeter, 95% CI: -19 to 25), and 18 months (24 cells per cubic millimeter, 95% CI: -13 to 61) compared with that gained by the KSHV- group. Adjusted relative risk of failure to suppress viral load to <400 copies per milliliter (1.03; 95% CI: 0.90 to 1.17) were similar for KSHV+ and KSHV- by 6 months on treatment. CONCLUSIONS In a population with a high KSHV prevalence, HIV-positive adults coinfected with KSHV achieved similar immunologic and virologic responses to ART early after treatment initiation compared with those with KSHV-.

Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study

BACKGROUND Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa. DESIGN Mathematical model based on longitudinal data from the Gugulethu and Khayelitsha township ART programmes in Cape Town, South Africa. METHODS Cohorts of patients on ART monitored by POC-VL, CD4 cell count or clinically were simulated. Scenario A considered the more accurate detection of treatment failure with POC-VL only, and scenario B also considered the effect on HIV transmission. Scenario C further assumed that the risk of virologic failure is halved with POC-VL due to improved adherence. We estimated the change in costs per quality-adjusted life-year gained (incremental cost-effectiveness ratios, ICERs) of POC-VL compared with CD4 and clinical monitoring. RESULTS POC-VL tests with detection limits less than 1000 copies/ml increased costs due to unnecessary switches to second-line ART, without improving survival. Assuming POC-VL unit costs between US$5 and US$20 and detection limits between 1000 and 10,000 copies/ml, the ICER of POC-VL was US$4010-US$9230 compared with clinical and US$5960-US$25540 compared with CD4 cell count monitoring. In Scenario B, the corresponding ICERs were US$2450-US$5830 and US$2230-US$10380. In Scenario C, the ICER ranged between US$960 and US$2500 compared with clinical monitoring and between cost-saving and US$2460 compared with CD4 monitoring. CONCLUSION The cost-effectiveness of POC-VL for monitoring ART is improved by a higher detection limit, by taking the reduction in new HIV infections into account and assuming that failure of first-line ART is reduced due to targeted adherence counselling.

Optimal time for initiating antiretroviral therapy (ART) in HIV-infected, treatment-naive children aged 2 to 5 years old

BACKGROUND The use of combination antiretroviral therapy (cART) comprising three antiretroviral medications from at least two classes of drugs is the current standard treatment for HIV infection in adults and children. Current World Health Organization (WHO) guidelines for antiretroviral therapy recommend early treatment regardless of immunologic thresholds or the clinical condition for all infants (less than one years of age) and children under the age of two years. For children aged two to five years current WHO guidelines recommend (based on low quality evidence) that clinical and immunological thresholds be used to identify those who need to start cART (advanced clinical stage or CD4 counts ≤ 750 cells/mm(3) or per cent CD4 ≤ 25%). This Cochrane review will inform the current available evidence regarding the optimal time for treatment initiation in children aged two to five years with the goal of informing the revision of WHO 2013 recommendations on when to initiate cART in children. OBJECTIVES To assess the evidence for the optimal time to initiate cART in treatment-naive, HIV-infected children aged 2 to 5 years. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the AEGIS conference database, specific relevant conferences, www.clinicaltrials.gov, the World Health Organization International Clinical Trials Registry platform and reference lists of articles. The date of the most recent search was 30 September 2012. SELECTION CRITERIA Randomised controlled trials (RCTs) that compared immediate with deferred initiation of cART, and prospective cohort studies which followed children from enrolment to start of cART and on cART. DATA COLLECTION AND ANALYSIS Two review authors considered studies for inclusion in the review, assessed the risk of bias, and extracted data on the primary outcome of death from all causes and several secondary outcomes, including incidence of CDC category C and B clinical events and per cent CD4 cells (CD4%) at study end. For RCTs we calculated relative risks (RR) or mean differences with 95% confidence intervals (95% CI). For cohort data, we extracted relative risks with 95% CI from adjusted analyses. We combined results from RCTs using a random effects model and examined statistical heterogeneity. MAIN RESULTS Two RCTs in HIV-positive children aged 1 to 12 years were identified. One trial was the pilot study for the larger second trial and both compared initiation of cART regardless of clinical-immunological conditions with deferred initiation until per cent CD4 dropped to <15%. The two trials were conducted in Thailand, and Thailand and Cambodia, respectively. Unpublished analyses of the 122 children enrolled at ages 2 to 5 years were included in this review. There was one death in the immediate cART group and no deaths in the deferred group (RR 2.9; 95% CI 0.12 to 68.9). In the subgroup analysis of children aged 24 to 59 months, there was one CDC C event in each group (RR 0.96; 95% CI 0.06 to 14.87) and 8 and 11 CDC B events in the immediate and deferred groups respectively (RR 0.95; 95% CI 0.24 to 3.73). In this subgroup, the mean difference in CD4 per cent at study end was 5.9% (95% CI 2.7 to 9.1). One cohort study from South Africa, which compared the effect of delaying cART for up to 60 days in 573 HIV-positive children starting tuberculosis treatment (median age 3.5 years), was also included. The adjusted hazard ratios for the effect on mortality of delaying ART for more than 60 days was 1.32 (95% CI 0.55 to 3.16). AUTHORS' CONCLUSIONS This systematic review shows that there is insufficient evidence from clinical trials in support of either early or CD4-guided initiation of ART in HIV-infected children aged 2 to 5 years. Programmatic issues such as the retention in care of children in ART programmes in resource-limited settings will need to be considered when formulating WHO 2013 recommendations.

Homicide-suicides compared to homicides and suicides: systematic review and meta-analysis.

Homicide-suicides, the murder of one or several individuals followed by the suicide of the perpetrator, are rare but have devastating effects on families and communities. We did a systematic review and meta-analysis of studies comparing perpetrators of homicide-suicides with perpetrators of simple homicides and suicides and examined the proportion of firearm use and its correlation with firearm availability. We searched Medline and Embase from inception to July 2012 and identified 27 eligible studies. Perpetrators of homicide-suicides were older and more likely to be male and married to or separated from their victims than perpetrator of simple homicides or suicides. Influence of alcohol and a history of domestic violence or unemployment were less prevalent in homicide-suicides than in homicides. The proportion of firearm use in homicide-suicides varied across countries and was highest in the USA, Switzerland and South Africa, followed by Australia, Canada, The Netherlands and England and Wales, with a strong correlation between the use of firearms and the level of civilian gun ownership in the country. Our results indicate that homicide-suicides represent a distinct entity, with characteristics distinguishing them both from homicides and suicides.

Musiktraditionen im Kontext moderner Globalisierungsprozesse und globaler Denkkonzepte

The documentation of music cultures and the research in and on “classic” regions like India, Indonesia, and Sub-Saharan Africa still plays a central role within ethnomusicological research. However, given the increasing impact of global processes, the central guiding questions of the discipline have undergone profound changes in recent years. Approaches towards globalization are highly varied: One dominant perspective – which can be described as “skeptical” – has equated globalization with musical homogenization. This perspective is still apparent in approaches in European folk music research, which focus on the preservation of “traditional” cultures. Besides hyperglobal perspectives, which perceive the emergence of global networks (hypermedia, mass media, cultural organizations) as a positive development, one can predominantly observe the emergence of transformationalist approaches in recent decades: Global interconnectedness is viewed as a (neutrally perceived) basis for the emergence of new musical structures here. The transformation of the discipline is also apparent in the shift of the historical perspective. Comparative Musicology had already developed a global-historical perspective, which, however, became problematic due to the lack of contextualization. This might explain the subsequent distanced stance taken towards global concepts. Yet the focus on oral cultures also neglected deeper analysis of the historical dimension. At present, one can observe the emergence of a – albeit highly differentiated – change of perspective. While the Anglo-American approaches encourage the development of a specifically ethnomusicological-historical methodology, this separation between ethnomusicological and historical topics is perceived as racist in countries like South Africa. Starting out with an analysis of the concept of canonization in ethnomusicology, this article not only provides an overview of the aforementioned approaches and developments, but also discusses the integration of these processes into ethnomusicologically informed music pedagogical teaching material – within both a school and university context.

Brief Report: How Adolescents with ASD Process Social Information in Complex Scenes. Combining Evidence from Eye Movements and Verbal Descriptions

We investigated attention, encoding and processing of social aspects of complex photographic scenes. Twenty-four high-functioning adolescents (aged 11–16) with ASD and 24 typically developing matched control participants viewed and then described a series of scenes, each containing a person. Analyses of eye movements and verbal descriptions provided converging evidence that both groups displayed general interest in the person in each scene but the salience of the person was reduced for the ASD participants. Nevertheless, the verbal descriptions revealed that participants with ASD frequently processed the observed person’s emotion or mental state without prompting. They also often mentioned eye-gaze direction, and there was evidence from eye movements and verbal descriptions that gaze was followed accurately. The combination of evidence from eye movements and verbal descriptions provides a rich insight into the way stimuli are processed overall. The merits of using these methods within the same paradigm are discussed.

The Beach in Anglophone Literatures and Cultures: Reading Littoral Space

From early colonial encounters to the ecological disasters of the twenty-first century, the performativity of contact has been a crucial element in the political significance of the beach. Conceptualising the beach as a creative trope and as a socio-cultural site, as well as an aesthetically productive topography, this collection examines its multiplicity of meanings and functions as a natural environment engendering both desire and fear in the human imagination from the Victorian period to the present. The contributors examine literature, film, and art, in addition to moments of encounter and environmental crisis, to highlight the beach as a social space inspiring particular codes of behaviour and specific discourses, as a geographical frontier between land and water, as an historical site of contact and conflict, and as a vacationscape promising regeneration and withdrawal from everyday life. The diversity of the beach is reflected in the geographical range, with essays on locales and texts from Britain, Ireland, the Caribbean, South Africa, the United States, Polynesia, and New Zealand. Focusing on the changed function of the beach as a result of processes of industrialisation and the rise of a modern leisure and health culture, this interdisciplinary volume theorises the beach as a demarcater of the precarious boundary between land and the sea, as well as between nature and culture.