IntroductionFourth generation (Ag/Ab combination) point of care HIV tests like the FDA-approved Determine HIV1/2 Ag/Ab Combo test offer the promise of timely detection of acute HIV infection, relevant in the context of HIV control. However, a synthesis of their performance has not yet been done. In this meta-analysis we not only assessed device performance but also evaluated the role of study quality on diagnostic accuracy.MethodsTwo independent reviewers searched seven databases, including conferences and bibliographies, and independently extracted data from 17 studies. Study quality was assessed with QUADAS-2. Data on sensitivity and specificity (overall, antigen, and antibody) were pooled using a Bayesian hierarchical random effects meta-analysis model. Subgroups were analyzed by blood samples (serum/plasma vs. whole blood) and study designs (case-control vs. cross-sectional).ResultsThe overall specificity of the Determine Combo test was 99.1%, 95% credible interval (CrI) [97.3–99.8]. The overall pooled sensitivity for the device was at 88.5%, 95% [80.1–93.4]. When the components of the test were analyzed separately, the pooled specificities were 99.7%, 95% CrI [96.8–100] and 99.6%, 95% CrI [99.0–99.8], for the antigen and antibody components, respectively. Pooled sensitivity of the antibody component was 97.3%, 95% CrI [60.7–99.9], and pooled sensitivity for the antigen component was found to be 12.3%, 95% (CrI) [1.1–44.2]. No significant differences were found between subgroups by blood sample or study design. However, it was noted that many studies restricted their study sample to p24 antigen or RNA positive specimens, which may have led to underestimation of overall test performance. Detection bias, selection (spectrum) bias, incorporation bias, and verification bias impaired study quality.ConclusionsAlthough the specificity of all test components was high, antigenic sensitivity will merit from an improvement. Besides the accuracy of the device itself, study quality, also impacts the performance of the test. These factors must be kept in mind in future evaluations of an improved device, relevant for global scale up and implementation.

Introduction Implementation data for digital unsupervised HIV self-testing (HIVST) are sparse. We evaluated the impact of an app-based, personalised, oral HIVST program offered by healthcare workers in Western Cape, South Africa. Methods In a quasirandomised study (n=3095), we recruited consenting adults with undiagnosed HIV infection from township clinics. To the HIVST arm participants (n=1535), we offered a choice of an offsite (home, office or kiosk based), unsupervised digital HIVST program (n=962), or an onsite, clinic-based, supervised digital HIVST program (n=573) with 24/7 linkages services. With propensity score analyses, we compared outcomes (ie, linkages, new HIV infections and test referrals) with conventional HIV testing (ConvHT) arm participants (n=1560), recruited randomly from geographically separated clinics. Results In both arms, participants were young (HIVST vs ConvHT) (mean age: 28.2 years vs 29.2 years), female (65.0% vs 76.0%) and had monthly income <3000 rand (80.8% vs 75%). Participants chose unsupervised HIVST (62.7%) versus supervised HIVST and reported multiple sex partners (10.88% vs 8.7%), exposure to sex workers (1.4% vs 0.2%) and fewer comorbidities (0.9% vs 1.9%). Almost all HIVST participants were linked (unsupervised HIVST (99.7%), supervised HIVST (99.8%) vs ConvHT (98.5%)) (adj RR 1.012; 95% CI 1.005 to 1.018) with new HIV infections: overall HIVST (9%); supervised HIVST (10.9%) and unsupervised HIVST (7.6%) versus ConvHT (6.79%) (adj RR 1.305; 95% CI 1.023 to 1.665); test referrals: 16.7% HIVST versus 3.1% ConvHT (adj RR 5.435; 95% CI 4.024 to 7.340). Conclusions Our flexible, personalised, app-based HIVST program, offered by healthcare workers, successfully linked almost all HIV self-testers, detected new infections and increased referrals to self-test. Data are relevant for digital HIVST initiatives worldwide.

BackgroundAlthough HIV self-testing strategies have been recommended by the World Health Organization, HIV self-tests are not yet approved in Canada. Currently approved HIV self-tests offer toll-free lines that are insufficient for initiating expedited linkages to counseling and care, accurate interpretation, and support during HIV self-testing. We developed an innovative, multilingual software app called HIVSmart! to plug these gaps.ObjectiveThis study aimed to test our app-optimized oral HIV self-testing strategy for feasibility in men who have sex with men (MSM) who presented to test at a large sexual health clinic (Clinique Médicale L’Actuel) in Montreal.MethodsBetween July 2016 and February 2017, we offered a strategy consisting of the OraQuick In-Home HIV Test (an investigational device) and a tablet installed with the HIVSmart! app to study participants, who presented at a private office in the clinic, mimicking an unsupervised home environment. We evaluated the strategy for its feasibility, acceptability, and preference. Using the HIVSmart! app, participants were guided through the self-testing process. We determined feasibility with a metric defined as the completion rate, which consisted of the following 3 steps: (1) self-test conduct; (2) self-test interpretation; and (3) linkages to care. Participants independently performed, interpreted, recorded their self-test and result, engaged in pre- and posttest counseling, and sought linkages to care. Laboratory tests (p24, Western Blot, and RNA), as per country algorithms, were expedited, and linkages based on the rapid test status were arranged.ResultsMean age of the 451 participants enrolled was 34 (range, 18-73) years. Of all participants, 97.1% (438/451) completed and submitted the survey through the HIVSmart! app. In total, 84.7% (371/438) of the participants were well educated (beyond high school) and 52.5% (230/438) had been tested within the past 6 months. Of the 451, 11.5% (52/451) were on pre-exposure prophylaxis. Feasibility (completion rate), an average proportion of the 3 steps, was computed to be 96.6% (419/451). The acceptability of the strategy was high at 98.5% (451/458). A majority of the participants (448/451, 99.3%) were found to be self-tested and lab-confirmed negative and were counseled after self- and rapid tests. In total, 0.7% (3/451) of the participants who self-tested positive and were lab-confirmed positive were linked to a physician within the same day. Furthermore, 98.8% (417/422) of the participants found the app to be useful and 94.0% (424/451) were willing to recommend it to a friend or partner.ConclusionsThe HIVSmart! app-optimized strategy was feasible, accepted, and preferred by an educated, urban MSM population of Montreal. With the app, participants were able to perform, interpret, store results, and get rapidly linked to care. The HIVSmart!-optimized, self-testing strategy could be adapted and contextualized to many at-risk populations within Canada and worldwide, thereby maximizing its public health impact.

In the adult brain only a small proportion of the neural stem and progenitor cells (NPCs) and their progeny survive to become mature neurons in the hippocampus. Recent studies have elucidated the roles for members of the B-cell lymphoma-2 (Bcl-2) family of proteins in regulating the survival of NPCs and their progeny at different stages of maturation, yet the requirement of Bcl-2 during this process remains unknown. Here we report that inducible removal of Bcl-2 from nestin-expressing neural stem/progenitor cells and their progeny resulted in a reduction in the survival of doublecortin-expressing cells in the absence of changing the number of radial-glial stem cells or dividing NPCs. The requirement of Bcl-2 for the survival of maturing NPCs was confirmed by removal of Bcl-2 through infecting NPCs using a retroviral strategy that resulted in the complete loss of Bcl-2 null cells by 30-day post-viral injection. Furthermore, we observed that the function of Bcl-2 in the adult-generated neurons was dependent on the Bcl-2-associated X (BAX) protein, since Bcl-2 null NPCs were rescued in BAX knockout mice. These results indicate that Bcl-2 is an essential regulator in the survival of doublecortin-expressing immature neurons through a mechanism that is upstream of BAX.

Human immunodeficiency virus (HIV) self-testing presents an empowering alternative to facility-based testing for reaching undiagnosed HIV infected individuals, but is not currently available in Canada. We surveyed stakeholders (clinical providers, public health professionals, researchers) engaged in HIV testing initiatives nationwide to identify the concerns, opportunities and challenges to implementing HIV self-testing in Canada. An online cross-sectional survey was disseminated by the Canadian Institutes of Health Research Centre for REACH 2.0 National HIV & sexually transmitted and blood borne infections working group to stakeholders nationwide, with a target sample size of 200. Quantitative and qualitative data were analyzed using a mixed-methods, respondent-informed approach, to inform subsequent HIV self-testing in a country where self-testing is not yet accessible. A total of 183 responses were received. A majority (70.7%) (128/181) felt that self-testing was a necessary investment to reach the undiagnosed. 64.6% (117/181) felt that self-tests should be made available to their clients and 71.5% (128/179) of respondents agreed that self-test instructions required improvements. However, 50% (90/180) felt that self-testing will pose an economic challenge to current HIV testing models. Regardless, 21% urged for timely action and availability of HIV self-tests. Thematic analyses reflected the following concerns: (a) need for affordable self-tests, (b) need for expedited, customized, and accessible linkages to counselling, (c) concern for patients to cope with positive self-test results, (d) accuracy of self-tests to detect acute HIV and (e) liability in the context of non-disclosure. Stakeholders agreed to the provision of an option of HIV self-testing to reach the undiagnosed individuals. Concerns regarding costs and accuracy of self-tests, expedited linkages to counselling, and integration of self-test within prevailing HIV testing models, will need to be addressed before their widespread implementation.