Baseline and primary data for the partner-provided HIV self-testing and linkage (PASTAL) adaptive multi-arm multi-stage cluster randomized trial in Blantyre, Malawi

Dataset containing details of 2,349 pregnant women accessing antenatal care in three primary health centres in urban Blantyre, Malawi who gave informed consent to participate in an adaptive multi-arm multi-stage cluster randomized trial. The unit of randomization was the antenatal care (ANC) clinic day. On a given ANC day, women could receive standard of care (SOC) of receiving just an invitation letter to deliver to their male partner who was absent at this ANC visit. Or, the women could receive SOC plus two oral self-test kits alone or in combination with a guaranteed financial incentive of $3 or$10 conditional on clinic attendance following self-testing for HIV care or prevention. Two other arms offered a lottery-based incentive with 10% chance of winning $30 to male partners achieving the primary outcome, or a phone call reminder to the male partner immediately following collection of kits by the woman repeated after five days. The dataset contains variables on baseline data for the women and their male partners as reported by the woman as well as data underlying the trial outcomes by arm. Recruitment and follow-up were completed between 8 August 2016 and 30 June 2017

Uptake, accuracy, safety and linkage into care over two years of promoting annual self-testing for HIV in Blantyre, Malawi: a community-based prospective study

A set of anonymised datasets produced in a community-based study to investigate self-testing for HIV in Blantyre, Malawi. Taken together the datasets enable replication of findings from the study including estimation of uptake of HIV self-testing (HIVST), analysis of sensitivity/specificity of self-reported self-test results compared to nurse-performed finger prick testing, and investigation of self-reported coercion to self-test

Initial Accuracy of HIV Rapid Test Kits Stored in Suboptimal Conditions and Validity of Delayed Reading of Oral Fluid Tests

An anonymised dataset produced as part of a study on initial accuracy of commonly used HIV rapid diagnostic tests (RDT) when stored in suboptimal conditions and the validity of delayed reading of OraQuick oral fluid tests. It contains HIV results for each RDT, age, sex, previous testing data and an indication of whether or not there was a change in the reading of OraQuick oral RDT over the 12 month period of re-reading. It may be used to validate results related to analysis of sensitivity and specificity of each sub-optimally-stored test kit compared with optimally stored Determine and Uni-Gold conducted in parallel

Scaling up HIV self-testing in sub-Saharan Africa: a review of technology, policy and evidence.

PURPOSE OF REVIEW: HIV self-testing (HIVST) can provide complementary coverage to existing HIV testing services and improve knowledge of status among HIV-infected individuals. This review summarizes the current technology, policy and evidence landscape in sub-Saharan Africa and priorities within a rapidly evolving field. RECENT FINDINGS: HIVST is moving towards scaled implementation, with the release of WHO guidelines, WHO prequalification of the first HIVST product, price reductions of HIVST products and a growing product pipeline. Multicountry evidence from southern and eastern Africa confirms high feasibility, acceptability and accuracy across many delivery models and populations, with minimal harms. Evidence on the effectiveness of HIVST on increased testing coverage is strong, while evidence on demand generation for follow-on HIV prevention and treatment services and cost-effective delivery is emerging. Despite these developments, HIVST delivery remains limited outside of pilot implementation. SUMMARY: Important technology gaps include increasing availability of more sensitive HIVST products in low and middle-income countries. Regulatory and postmarket surveillance systems for HIVST also require further development. Randomized trials evaluating the effectiveness and cost-effectiveness under multiple distribution models, including unrestricted delivery and with a focus on linkage to HIV prevention and treatment, remain priorities. Diversification of studies from west and central Africa and around blood-based products should be addressed

Autophagy enhances memory erasure through synaptic destabilization

There is substantial interest in memory reconsolidation as a target for the treatment of anxiety disorders, such as post-traumatic stress disorder. However, its applicability is restricted by reconsolidation-resistant boundary conditions that constrain the initial memory destabilization. In this study, we investigated whether the induction of synaptic protein degradation through autophagy modulation, a major protein degradation pathway, can enhance memory destabilization upon retrieval and whether it can be used to overcome these conditions. Here, using male mice in an auditory fear reconsolidation model, we showed that autophagy contributes to memory destabilization and its induction can be used to enhance erasure of a reconsolidation-resistant auditory fear memory that depended on AMPAR endocytosis. Using male mice in a contextual fear reconsolidation model, autophagy induction in the amygdala or in the hippocampus enhanced fear or contextual memory destabilization, respectively. The latter correlated with AMPAR degradation in the spines of the contextual memory-ensemble cells. Using male rats in an in vivo LTP reconsolidation model, autophagy induction enhanced synaptic destabilization in an NMDAR-dependent manner. These data indicate that induction of synaptic protein degradation can enhance both synaptic and memory destabilization upon reactivation and that autophagy inducers have the potential to be used as a therapeutic tool in the treatment of anxiety disorders

Synapse-specific representation of the identity of overlapping memory engrams

Memories are integrated into interconnected networks; nevertheless, each memory has its own identity. How the brain defines specific memory identity out of intermingled memories stored in a shared cell ensemble has remained elusive. We found that after complete retrograde amnesia of auditory fear conditioning in mice, optogenetic stimulation of the auditory inputs to the lateral amygdala failed to induce memory recall, implying that the memory engram no longer existed in that circuit. Complete amnesia of a given fear memory did not affect another linked fear memory encoded in the shared ensemble. Optogenetic potentiation or depotentiation of the plasticity at synapses specific to one memory affected the recall of only that memory. Thus, the sharing of engram cells underlies the linkage between memories, whereas synapse-specific plasticity guarantees the identity and storage of individual memories

Cost and quality of life analysis of HIV self-testing and facility-based HIV testing and counselling in Blantyre, Malawi

Background HIV self-testing (HIVST) has been found to be highly effective, but no cost analysis has been undertaken to guide the design of affordable and scalable implementation strategies. Methods Consecutive HIV self-testers and facility-based testers were recruited from participants in a community cluster-randomised trial (ISRCTN02004005) investigating the impact of offering HIVST in addition to facility-based HIV testing and counselling (HTC). Primary costing studies were undertaken of the HIVST service and of health facilities providing HTC to the trial population. Costs were adjusted to 2014 USD and INT$. Recruited participants were asked about direct non-medical and indirect costs associated with accessing either modality of HIV testing, and additionally their health-related quality of life was measured using the EuroQol EQ-5D. Results A total of 1,241 participants underwent either HIVST (nandthinsp;=andthinsp;775) or facility-based HTC (nandthinsp;=andthinsp;446). The mean societal cost per participant tested through HIVST (USD9.23; 95 % CI: USD9.14-USD9.32) was lower than through facility-based HTC (USD11.84; 95 % CI: USD10.81-12.86). Although the mean health provider cost per participant tested through HIVST (USD8.78) was comparable to facility-based HTC (range: USD7.53-USD10.57), the associated mean direct non-medical and indirect cost was lower (USD2.93; 95 % CI: USD1.90-USD3.96). The mean health provider cost per HIV positive participant identified through HIVST was higher (USD97.50) than for health facilities (range: USD25.18-USD76.14), as was the mean cost per HIV positive individual assessed for anti-retroviral treatment (ART) eligibility and the mean cost per HIV positive individual initiated onto ART. In comparison to the facility-testing group, the adjusted mean EQ-5D utility score was 0.046 (95 % CI: 0.022-0.070) higher in the HIVST group. Conclusions HIVST reduces the economic burden on clients, but is a costlier strategy for the health provider aiming to identify HIV positive individuals for treatment. The provider cost of HIVST could be substantially lower under less restrictive distribution models, or if costs of oral fluid HIV test kits become comparable to finger-prick kits used in health facilities.</p

Uptake, Accuracy, Safety, and Linkage into Care over Two Years of Promoting Annual Self-Testing for HIV in Blantyre, Malawi: A Community-Based Prospective Study

Background Home-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population. Methods and Findings Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test) to adult (≥16 y old) residents (n = 16,660) and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA) sample. Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover) residents self-tested during months 1–12, with adolescents (16–19 y) most likely to test. 10,614/14,004 (75.8%) participants shared results with volunteer-counsellors. Of 1,257 (11.8%) HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3%) newly accessed care with a median CD4 count of 250 cells/μl (interquartile range 159–426). HIVST uptake in months 13–24 was more rapid (70.9% uptake by 6 mo), with fewer (7.3%, 95% CI 6.8%–7.8%) positive participants. Being “forced to test”, usually by a main partner, was reported by 2.9% (95% CI 2.6%–3.2%) of 10,017 questionnaire respondents in months 1–12, but satisfaction with HIVST (94.4%) remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1,649 systematically selected (1 in 20) QA participants (99.4%), giving a sensitivity of 93.6% (95% CI 88.2%–97.0%) and a specificity of 99.9% (95% CI 99.6%–100%). Key limitations included use of aggregate data to report uptake of HIVST and being unable to adjust for population turnover. Conclusions Community-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings

Reflecting on Academic Freedom Through Fiction: A Theatrical Exploration of the Blurry Contours of the Freedom to Teach

This article aims at exploring the contribution that creative forms of research can make to the study of a little-known aspect of academic freedom in the Canadian context – academic freedom in curriculum development. It seeks to address the methodological challenge posed by research on academic freedom, that is, the fact that any academic writing on this topic necessarily draws initially, though not exclusively, from the researchers’ own experiences and perspectives. The article brings to life a fictional faculty meeting, during which questions about academic freedom in teaching are discussed. Although this meeting is the product of our imagination, its starting point is based on real-life events, that is, the implementation in some North American universities of a course developed and initially offered outside of academia by people closely related to a well-known personal development organization