Self-tests for COVID-19: What is the evidence? A living systematic review and meta-analysis (2020-2023).

COVID-19 self-testing strategy (COVIDST) can rapidly identify symptomatic and asymptomatic SARS-CoV-2-infected individuals and their contacts, potentially reducing transmission. In this living systematic review, we evaluated the evidence for real-world COVIDST performance. Two independent reviewers searched six databases (PubMed, Embase, Web of Science, World Health Organization database, Cochrane COVID-19 registry, Europe PMC) for the period April 1st, 2020, to January 18th, 2023. Data on studies evaluating COVIDST against laboratory-based conventional testing and reported on diagnostic accuracy, feasibility, acceptability, impact, and qualitative outcomes were abstracted. Bivariate random effects meta-analyses of COVIDST accuracy were performed (n = 14). Subgroup analyses (by sampling site, symptomatic/asymptomatic infection, supervised/unsupervised strategy, with/without digital supports) were conducted. Data from 70 included studies, conducted across 25 countries with a median sample size of 817 (range: 28-784,707) were pooled. Specificity and DOR was high overall, irrespective of subgroups (98.37-99.71%). Highest sensitivities were reported for: a) symptomatic individuals (73.91%, 95%CI: 68.41-78.75%; n = 9), b) mid-turbinate nasal samples (77.79%, 95%CI: 56.03-90.59%; n = 14), c) supervised strategy (86.67%, 95%CI: 59.64-96.62%; n = 13), and d) use of digital interventions (70.15%, 95%CI: 50.18-84.63%; n = 14). Lower sensitivity was attributed to absence of symptoms, errors in test conduct and absence of supervision or a digital support. We found no difference in COVIDST sensitivity between delta and omicron pre-dominant period. Digital supports increased confidence in COVIDST reporting and interpretation (n = 16). Overall acceptability was 91.0-98.7% (n = 2) with lower acceptability reported for daily self-testing (39.5-51.1%). Overall feasibility was 69.0-100.0% (n = 5) with lower feasibility (35.9-64.6%) for serial self-testing. COVIDST decreased closures in school, workplace, and social events (n = 4). COVIDST is an effective rapid screening strategy for home-, workplace- or school-based screening, for symptomatic persons, and for preventing transmission during outbreaks. These data will guide COVIDST policy. Our review demonstrates that COVIDST has paved the way for self-testing in pandemics worldwide.

Development and Evaluation of a Digital HIV Risk Assessment Tool Incorporated Within an App-Based Self-Testing Program.

BACKGROUND: Low-risk perception is an important barrier to the utilization of HIV services. In this context, offering an online platform for people to assess their risk of HIV and inform their decision to test can be impactful in increasing testing uptake. Using secondary data from the HIVSmart! quasirandomized trial, we aimed to identify predictors of HIV, develop a risk staging model for South African township populations, and validate it in combination with the HIVSmart! digital self-testing program. SETTING: Townships in Cape Town, South Africa. METHODS: Using Bayesian predictive projection, we identified predictors of HIV and constructed a risk assessment model that we validated in external data. RESULTS: Our analyses included 3095 participants from the HIVSmart! trial. We identified a model of 5 predictors (being unmarried, HIV testing history, having had sex with a partner living with HIV, dwelling situation, and education) that performed best during external validation (area under the receiver operating characteristic curve, 89% credible intervals: 0.71, 0.68 to 0.72). The sensitivity of our HIV risk staging model was 91.0% (89.1% to 92.7%) and the specificity was 13.2% (8.5% to 19.8%) but increased when combined with a digital HIV self-testing program, the specificity was 91.6% (95.9% to 96.4%) and sensitivity remained similar at 90.9% (89.1% to 92.6%). CONCLUSIONS: This is the first validated digital HIV risk assessment tool developed for South African township populations and the first study to evaluate the added value of a risk assessment tool with an app-based HIV self-testing program. Study findings are relevant for application of digital programs to improve utilization of HIV testing services.

Self-sampling strategies (with/without digital innovations) in populations at risk of Chlamydia trachomatis and Neisseria gonorrhoeae: a systematic review and meta-analyses.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) resulted in over 200 million new sexually transmitted infections last year. Self-sampling strategies alone or combined with digital innovations (ie, online, mobile or computing technologies supporting self-sampling) could improve screening methods. Evidence on all outcomes has not yet been synthesised, so we conducted a systematic review and meta-analysis to address this limitation. METHODS: We searched three databases (period: 1 January 2000-6 January 2023) for reports on self-sampling for CT/GC testing. Outcomes considered for inclusion were: accuracy, feasibility, patient-centred and impact (ie, changes in linkage to care, first-time testers, uptake, turnaround time or referrals attributable to self-sampling).We used bivariate regression models to meta-analyse accuracy measures from self-sampled CT/GC tests and obtain pooled sensitivity/specificity estimates. We assessed quality with Cochrane Risk of Bias Tool-2, Newcastle-Ottawa Scale and Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: We summarised results from 45 studies reporting self-sampling alone (73.3%; 33 of 45) or combined with digital innovations (26.7%; 12 of 45) conducted in 10 high-income (HICs; n=34) and 8 low/middle-income countries (LMICs; n=11). 95.6% (43 of 45) were observational, while 4.4% (2 of 45) were randomised clinical trials.We noted that pooled sensitivity (n=13) for CT/GC was higher in extragenital self-sampling (>91.6% (86.0%-95.1%)) than in vaginal self-sampling (79.6% (62.1%-90.3%)), while pooled specificity remained high (>99.0% (98.2%-99.5%)).Participants found self-sampling highly acceptable (80.0%-100.0%; n=24), but preference varied (23.1%-83.0%; n=16).Self-sampling reached 51.0%-70.0% (n=3) of first-time testers and resulted in 89.0%-100.0% (n=3) linkages to care. Digital innovations led to 65.0%-92% engagement and 43.8%-57.1% kit return rates (n=3).Quality of studies varied. DISCUSSION: Self-sampling had mixed sensitivity, reached first-time testers and was accepted with high linkages to care. We recommend self-sampling for CT/GC in HICs but additional evaluations in LMICs. Digital innovations impacted engagement and may reduce disease burden in hard-to-reach populations. PROSPERO REGISTRATION NUMBER: CRD42021262950.

Socioeconomic factors impact the risk of HIV acquisition in the township population of South Africa: A Bayesian analysis.

With a prevalence almost twice as high as the national average, people living in South African townships are particularly impacted by the HIV epidemic. Yet, it remains unclear how socioeconomic factors impact the risk of HIV infection within township populations. Our objective was to estimate the extent to which socioeconomic factors (dwelling situation, education, employment status, and monthly income) explain the risk of HIV in South African township populations, after controlling for behavioural and individual risk factors. Using Bayesian logistic regression, we analysed secondary data from a quasi-randomised trial which recruited participants (N = 3095) from townships located across three subdistricts of Cape Town. We controlled for individual factors (age, sex, marital status, testing history, HIV exposure, comorbidities, and tuberculosis infection) and behavioural factors (unprotected sex, sex with multiple partners, with sex workers, with a partner living with HIV, under the influence of alcohol or drugs), and accounted for the uncertainty due to missing data through multiple imputation. We found that residing in informal dwellings and not having post-secondary education increased the odds of HIV (aOR, 89% CrI: 1.34, 1.07-1.68 and 1.82, 1.29-2.61, respectively), after controlling for subdistrict of residence, individual, and behavioural factors. Additionally, our results suggest different pathways for how socioeconomic status (SES) affect HIV infection in males and female participants: while socioeconomic factors associated with lower SES seem to be associated with a decreased likelihood of having recently sough HIV testing among male participants, they are associated with increased sexual risk taking which, among female participants, increase the risk of HIV. Our analyses demonstrate that social determinants of health are at the root of the HIV epidemic and affect the risk of HIV in multiple ways. These findings stress the need for the deployment of programs that specifically address social determinants of health.

Prioritizing gender equity and intersectionality in Canadian global health institutions and partnerships.

Despite governmental efforts to close the gender gap and global calls including Sustainable Development Goal 5 to promote gender equality, the sobering reality is that gender inequities continue to persist in Canadian global health institutions. Moreover, from health to the economy, security to social protection, COVID-19 has exposed and heightened pre-existing inequities, with women, especially marginalized women, being disproportionately impacted. Women, particularly women who face bias along multiple identity dimensions, continue to be at risk of being excluded or delegitimized as participants in the global health workforce and continue to face barriers in career advancement to leadership, management and governance positions in Canada. These inequities have downstream effects on the policies and programmes, including global health efforts intended to support equitable partnerships with colleagues in low- and middle- income countries. We review current institutional gender inequities in Canadian global health research, policy and practice and by extension, our global partnerships. Informed by this review, we offer four priority actions for institutional leaders and managers to gender-transform Canadian global health institutions to accompany both the immediate response and longer-term recovery efforts of COVID-19. In particular, we call for the need for tracking indicators of gender parity within and across our institutions and in global health research (e.g., representation and participation, pay, promotions, training opportunities, unpaid care work), accountability and progressive action.

Global Health Facility-Based Interventions to Achieve UNAIDS 90-90-90: A Systematic Review and Narrative Analysis.

To evaluate whether health facility-based HIV interventions align with UNAIDS 90-90-90 targets, we performed a systematic review through the lens of UNAIDS targets. We searched 11 databases, retrieving 5201 citations with 26 eligible studies classified by country income and UNAIDS target. We analyzed whether reporting of study outcome metrics was in line with UNAIDS targets using a standardized extraction form and results were summarized in a narrative synthesis given data heterogeneity. We also assessed the quality of randomized trials with the Cochrane Risk of Bias Tool and observational studies with the Newcastle-Ottawa Scale. Stratification of interventions by country income level revealed themes in successful interventions that provide insight for scale-up in similar resource contexts. Few studies reported outcomes using metrics according to UNAIDS targets. Standardization of reporting according to the UNAIDS framework could facilitate comparability of interventions and inform country-level progress on an international scale.

Implementation of an electronic patient-reported measure of barriers to antiretroviral therapy adherence with the Opal patient portal: Protocol for a mixed method type 3 hybrid pilot study at a large Montreal HIV clinic.

BACKGROUND: Adherence to antiretroviral therapy (ART) remains problematic. Regular monitoring of its barriers is clinically recommended, however, patient-provider communication around adherence is often inadequate. Our team thus decided to develop a new electronically administered patient-reported outcome measure (PROM) of barriers to ART adherence (the I-Score) to systematically capture this data for physician consideration in routine HIV care. To prepare for a controlled definitive trial to test the I-Score intervention, a pilot study was designed. Its primary objectives are to evaluate patient and physician perceptions of the I-Score intervention and its implementation strategy. METHODS: This one-arm, 6-month study will adopt a mixed method type 3 implementation-effectiveness hybrid design and be conducted at the Chronic Viral Illness Service of the McGill University Health Centre (Montreal, Canada). Four HIV physicians and 32 of their HIV patients with known or suspected adherence problems will participate. The intervention will involve having patients complete the I-Score through a smartphone application (Opal), before meeting with their physician. Both patients and physicians will have access to the I-Score results, for consideration during the clinic visits at Times 1, 2 (3 months), and 3 (6 months). The implementation strategy will focus on stakeholder involvement, education, and training; promoting the intervention's adaptability; and hiring an Application Manager to facilitate implementation. Implementation, patient, and service outcomes will be collected (Times 1-2-3). The primary outcome is the intervention's acceptability to patients and physicians. Qualitative data obtained, in part, through physician focus groups (Times 2-3) and patient interviews (Times 2-3) will help evaluate the implementation strategy and inform any methodological adaptations. DISCUSSION: This study will help plan a definitive trial to test the efficacy of the I-Score intervention. It will generate needed data on electronic PROM interventions in routine HIV care that will help improve understanding of conditions for their successful implementation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04702412; https://clinicaltrials.gov/.

An observed, prospective field study to evaluate the performance and acceptance of a blood-based HIV self-test in Canada.

BACKGROUND: Self testing for HIV is a targeted intervention with the potential to increase the access, uptake and frequency of HIV testing and more effectively reach the undiagnosed, especially in priority populations. The objectives of this study were to (1) evaluate the INSTI HIV self-test performance compared with laboratory reference testing, (2) document if intended users can perform the steps to use the HIV self-test device, and (3) document if intended users can successfully interpret contrived positive, negative, and invalid results. Study was intended to be submitted to Health Canada for review for regulatory approval purposes. METHODS: The study used a cross-sectional design and recruited consenting adults who were representative of intended users of HIV self-testing from four community sites across Ontario, Québec, and Manitoba between August 2019 and March 2020. The results of the observed HIV self-test were compared with results of the Abbott Architect HIV Ag/Ab Combo test. Usability outcomes for critical (e.g., lancing finger, blood droplet into bottle, shaking bottle four times) and noncritical self-test procedure steps were also determined. RESULTS: Overall, 77% (n = 522) of participants were between 18 and 45 years of age, 61% (n = 410) were male, 71% (n = 480) had some college or more education, and 45% (n = 307) were employed; identity for race and ethnicity: Caucasian (44%; n = 296), African, Caribbean or Black (17%; n = 113), Indigenous [First Nations, Métis or Inuit] (14%; n = 95), Asian (16%; n = 106), Latin American (7%; n = 46). Primary performance analysis on 678 completed HIV self-tests revealed a positive percent agreement of 100% (5/5, 95% CI: 43.6-97.0%) and a negative percent agreement of 99.5% (614/617, 95% CI: 98.6-99.8%) with the comparator method. The overall percent agreement of results interpretation between participant and observer was 93.5% (n = 633). For the 708 participants who took part in the usability study, the average success rate for steps determined to be "critical" for successful completion of the test was 92.4%. 97% (n = 670) of participants found the instructions easy to follow, and 95% (n = 655) of participants indicated that they would use the test again. Of the 404 participants who interpreted the strong positive, weak positive, negative, and invalid contrived results, successful interpretation ranged from 90.6% (for weak positive, n = 366) to 99.3% (for negative, n = 401). CONCLUSIONS: The addition of a regulatory-approved self-test into the Canadian HIV testing landscape could significantly increase HIV testing rates. Having a blood-based HIV self-test approved in Canada can offer an accurate, acceptable, and simple alternative to facility-based HIV testing, particularly when impacted by Coronavirus pandemic restrictions.

'You're only there on the phone'? A qualitative exploration of community, affect and agential capacity in HIV self-testing using a smartphone app.

Mobile health (mHealth) technologies for HIV care are developed to provide diagnostic support, health education, risk assessment and self-monitoring. They aim to either improve or replace part of the therapeutic relationship. Part of the therapeutic relationship is affective, with the emergence of feelings and emotion, yet little research on mHealth for HIV care focuses on affect and HIV testing practices. Furthermore, most of the literature exploring affect and care relations with the introduction of mHealth is limited to the European and Australian context. This article explores affective dimensions of HIV self-testing using a smartphone app strategy in Cape Town, South Africa and Montréal, Canada. This study is based on observation notes, 41 interviews and 1 focus group discussion with study participants and trained HIV healthcare providers from two quantitative studies evaluating the app-based self-test strategy. Our paper reveals how fear, apathy, judgement, frustration and comfort arise in testing encounters using the app and in previous testing experiences, as well as how this relates to care providers and test materials. Attending to affective aspects of this app-based self-testing practice makes visible certain affordances and limitations of the app within the therapeutic encounter and illustrates how mHealth can contribute to HIV care.

Which community-based HIV initiatives are effective in achieving UNAIDS 90-90-90 targets? A systematic review and meta-analysis of evidence (2007-2018).

BACKGROUND: Reaching the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets to end the HIV epidemic relies on effective interventions that engage untested HIV+ individuals and retain them in care. Evidence on community-based interventions through the lens of the targets has not yet been synthesized, reflecting a knowledge gap. We conducted a systematic review and meta-analysis to shed light on successful community-based interventions that have been effective in contributing, directly or indirectly, towards the UNAIDS 90-90-90 targets: knowledge of HIV status, linkage to care/on treatment, and viral suppression. Linkage to care was also included in this review due to the limitations of studies. METHODS: We conducted a systematic review and meta-analysis of the period 2007-2018. Eleven databases were searched to identify community-based interventions designed to improve knowledge of HIV status (in particular HIV testing), linkage to care/on treatment, and/or viral suppression. Eligible studies were classified by intervention, population, country income level, outcomes and success. Success was defined as interventions demonstrating statistical significance between intervention and control group or that reached any target by proportion; 90% testing, 81% linked to care/on treatment and 73% viral suppression. RESULTS: Of 82 eligible studies, 51.2% (42/82) reported on HIV testing (first 90), 20.7% (17/82) on linkage to care/ on treatment (second 90), and 45.1% (37/82) on viral suppression (third 90). In all, 67.1% (55/82) of studies reported success; 21 studies on the first 90, 9 towards linkage to care/on treatment, and 25 towards the third. By strategies, 36.6% deployed community workers/peers, 22% used combined test and treat strategies, 12.2% used educational methods, 8.5% used mobile testing, 7.3% used campaigns and 13.4% used technology. For HIV testing/linkage, combined test/treat interventions were often used, for viral suppression, educational interventions and technologies were commonly deployed. Our pooled analysis suggested that deployment of community health care workers/peer workers significantly improved viral suppression (pooled OR: 1.40 95% CI 1.06-1.86). Of the studies published after 2014, 50.0% reported metrics aligned with UNAIDS targets. CONCLUSIONS: Data on linkage to care/on treatment (second target) remained weak, because many studies reported successes on the first and third targets. Stratification by targets and country income levels is informative and guides adaptation of successful interventions in comparable settings. Consistent reporting of clear metrics aligned with UNAIDS targets will aid in synergy of study data with programmatic data that will help reportage. Exploration of innovative interventions, for engagement and linkage and deployment of community/ peer workers is strongly encouraged.

Are policy initiatives aligned to meet UNAIDS 90-90-90 targets impacting HIV testing and linkages to care? Evidence from a systematic review.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS (UNAIDS) Fast-Track initiative seeks to eliminate AIDS as a health threat by 2030, with its focus on UNAIDS 90-90-90 targets. Effective policies and programs, if scaled nationally, have the potential to generate a greater impact on HIV control, yet a synthesis of successful HIV policies/programs aligned to the targets is currently unavailable. To fill this gap, we conducted a systematic review to evaluate successful HIV policies and programs to direct future interventions. METHODS: For the period 2007-2018, we searched 8 databases and classified eligible studies by country income level, UNAIDS targets, intervention type, and reported outcomes. Study outcomes were classified as per UNAIDS targets; proportionally: 90% target 1, 81% target 2, and 73% target 3. RESULTS: We retrieved 5201 citations and a final set of eight studies on policies. Break up by income: three (38%) from high income, one (12%) from middle income and four (50%) from low income. Break up by outcomes reported: 36% (4/11) focused on HIV testing, 46% (5/11) on antiretroviral therapy initiation, and 18% (2/11) on viral suppression. Across studies, UNAIDS targets were met in high-income countries, where policies and guidelines were adhered to, whereas in low and middle-income countries, non-adherence led to failure to reach the targets. Targets were also met when country infrastructure supported a targeted program and stakeholders were actively engaged. CONCLUSIONS: From the studies identified, we deduced a clear, positive correlation between implementation of policies and programs that resulted in an increase in patient awareness and an increase in partner notification with services that encouraged them, and together these resulted in increasing testing rates, and deployment of linkage/retention programs that improved retention in care. An analysis of these studies also suggests that policies, combined with the scale-up incentives, are needed to change the status quo. Incentives to improve the targets must exist; performance incentives at the health care worker level and country level incentives that could transform the nature of care. Given the complexity in reporting of targets, a one size fits all model is not a feasible option. However, the policies created a strong framework to shape future interventions.

Will an innovative connected AideSmart! app-based multiplex, point-of-care screening strategy for HIV and related coinfections affect timely quality antenatal screening of rural Indian women? Results from a cross-sectional study in India.

OBJECTIVES: In rural pregnant Indian women, multiple missed antenatal screening opportunities due to inadequate public health facility-based screening result in undiagnosed HIV and sexually transmitted bloodborne infections (STBBIs) and conditions (anaemia). Untreated infections complicate pregnancy management, precipitate adverse outcomes and risk mother-to-child transmission. Additionally, a shortage of trained doctors, rural women's preference for home delivery and health illiteracy affect health service delivery. To address these issues, we developed AideSmart!, an innovative, app-based, cloud-connected, rapid screening strategy that offers multiplex screening for STBBIs and anaemia at the point of care. It offers connectivity, integration, expedited communications and linkages to clinical care throughout pregnancy. METHODS: In a cross-sectional study, we evaluated the AideSmart! strategy for feasibility, acceptability, preference and impact. We trained 15 healthcare professionals (HCPs) to offer the AideSmart! strategy to 510 pregnant women presenting for care to outreach rural service units of Christian Medical College, Vellore, India. RESULTS: With the AideSmart! screening strategy, we recorded an acceptability of 100% (510/510), feasibility (completion rate) of 91.6% (466/510) and preference of 73%. We detected 239 infections/conditions (239/510, 46.8%) at the point-of-care, of which 168 (168/239; 70%) were lab confirmed, staged and treated rapidly. Of the 168 confirmed infections/conditions, 127 were anaemia, 11 Trichomonas and 30 hepatitis B virus (HBV) (25 resolved naturally, 5 active infections). Four infants (4/5; 80%) were prophylaxed for HBV and were declared disease-free at 9 months. Recruited participants were young; mean age was 24 years (range: 17-40) and 74% (376/510) were in their second trimester. Furthermore, 95% of the participants were retained throughout their pregnancy. CONCLUSION: The AideSmart! strategy was deemed feasible to operationalise by HCPs. It was accepted and preferred by participants, resulting in timely screening and treatment of HIV/STIs and anaemia, preventing mother-to-child transmission. The strategy could be reverse-innovated to any context to maximise its health impact.

An Unsupervised Smart App-Optimized HIV Self-Testing Program in Montreal, Canada: Cross-Sectional Study.

BACKGROUND: Although 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. OBJECTIVE: This 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. METHODS: Between 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. RESULTS: Mean 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. CONCLUSIONS: The 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.

Systematic reviews of point-of-care tests for the diagnosis of urogenital Chlamydia trachomatis infections.

BACKGROUND: WHO estimates that 131 million new cases of urogenital Chlamydia trachomatis (CT) infections occur globally every year. Most infections are asymptomatic. Untreated infection in women can lead to severe complications. Screening and treatment of at-risk populations is a priority for prevention and control. OBJECTIVES: To summarise systematic reviews of the performance characteristics of commercially available point-of-care tests (POCT) for screening and diagnosis of urogenital CT infection. METHODS: Two separate systematic reviews covering the periods 2004-2013 and 2010-2015 were conducted on rapid CT POCTs. Studies were included if tests were evaluated against a valid reference standard. RESULTS: In the first review, 635 articles were identified, of which 11 were included. Nine studies evaluated the performance of eight antigen detection rapid POCTs on 10 280 patients and two studies evaluated a near-patient nucleic acid amplification test (NAAT) on 3518 patients. Pooled sensitivity of antigen detection tests was 53%, 37% and 63% for cervical swabs, vaginal swabs and male urine, and specificity was 99%, 97% and 98%, respectively. The pooled sensitivity and specificity of the near-patient NAAT for all specimen types were >98% and 99.4%, respectively. The second review identified two additional studies on four antigen detection POCTs with sensitivities and specificities of 22.7%-37.7% and 99.4%-100%, respectively. A new two-step 15 min rapid POCT using fluorescent nanoparticles showed performance comparable to that of near-patient NAATs. CONCLUSIONS: The systematic reviews showed that antigen detection POCTs for CT, although easy to use, lacked sufficient sensitivity to be recommended as a screening test. A near-patient NAAT shows acceptable performance as a screening or diagnostic test but requires electricity, takes 90 min and is costly. More affordable POCTs are in development.

A systematic review and meta-analysis of studies evaluating the performance of point-of-care tests for human papillomavirus screening.

BACKGROUND: High-risk human papillomavirus (HPV) is a necessary cause of high-grade cervical intraepithelial neoplasia (grade 2 or higher, CIN2+). Simplified and rapid HPV DNA assays designed for use in resource-limited settings have recently become available. METHODS: We performed a systematic review and meta-analysis by searching Medline, Embase, Global Health and CINAHL databases for studies from 1 January 2004 to 25 February 2017 that reported the performance of careHPV or OncoE6 for the detection of histological CIN2+ in cervical cancer screening. We used bivariate models to estimate pooled sensitivity and specificity for CIN2+ and CIN3+. RESULTS: A total of 29 657 women were included from seven studies evaluating the performance of careHPV for the detection of CIN2+ and four studies among 27 845 women for the detection of CIN3+. The pooled prevalence for CIN2+ and CIN3+ was 2.3% and 1.1%, respectively. careHPV had sensitivity and specificity of 88.1% (95% CI 81.4 to 92.7) and 83.7% (95% CI 74.9 to 89.8), respectively, for CIN2+ and 90.3% (95% CI 83.4 to 94.5) and 85.3% (95% CI 73.1 to 92.5), respectively, for CIN3+, using clinician-collected cervical specimen. The corresponding pooled estimates using self-collected vaginal swabs were 73.6% (95% CI 64.9 to 80.8) and 88.0% (95% CI 79.1 to 93.5) for CIN2+ and 75.2% (95% CI 66.8 to 82.0) and 90.6% (95% CI 83.4 to 94.9) for CIN3+. Two studies using OncoE6 reported sensitivity and specificity ranging from 31.3% to 42.4% and 99.1%-99.4% for CIN2+, and 53.5% and 98.9% for CIN3+ for one study. CONCLUSION: CareHPV has good sensitivity and specificity for the detection of CIN2+ and CIN3+, but sensitivity was lower using self-collected vaginal samples. The specificity is lower in high HPV prevalence populations such as women living with HIV. OncoE6 assay warrants further evaluation.

How patients navigate the diagnostic ecosystem in a fragmented health system: a qualitative study from India.

BACKGROUND: Depending on a country's diagnostic infrastructure, patients and providers play different roles in ensuring that correct and timely diagnosis is made. However, little is known about the work done by patients in accessing diagnostic services and completing the 'test and treat' loop. OBJECTIVE: To address this knowledge gap, we traced the diagnostic journeys of patients with tuberculosis, diabetes, hypertension and typhoid, and examined the work they had to do to arrive at a diagnosis. METHODS: This paper draws on a qualitative study, which included 78 semi-structured interviews and 13 focus group discussions with patients, public and private healthcare providers, community health workers, test manufacturers, laboratory technicians, program managers and policymakers. Data were collected between January and June 2013 in rural and urban Karnataka, South India, as part of a larger project on barriers to point-of-care testing. We reconstructed patient diagnostic processes retrospectively and analyzed emerging themes and patterns. RESULTS: The journey to access diagnostic services requires a high level of involvement and immense work from patients and/or their caretakers. This process entails overcoming cost and distance, negotiating social relations, continuously making sense of their illness and diagnosis, producing and transporting samples, dealing with the social consequences of diagnosis, and returning results to the treating provider. The quality and content of interactions with providers were crucial for completion of test and treat loops. If the tasks became overwhelming, patients opted out, delayed being tested, switched providers and/or reverted to self-testing or self-treatment practices. CONCLUSION: Our study demonstrated how difficult it can be for patients to complete diagnostic journeys and how the health system works as far as diagnostics are concerned. If new point-of-care tests are to be implemented successfully, policymakers, program officers and test developers need to find ways to ease patient navigation through diagnostic services.

Making HIV testing work at the point of care in South Africa: a qualitative study of diagnostic practices.

BACKGROUND: Point of care testing promises to reduce delays in diagnosing and initiating treatment for infectious diseases such as Human Immuno-deficiency Virus (HIV). In South Africa, decentralized HIV testing with rapid tests offers important lessons for point of care testing programs. Yet, little is known about the strategies of providers and clients to make HIV testing successful in settings short of equipment, human resources and space. We aimed at examining these strategies. METHODS: This paper is based on a larger qualitative study of diagnostic practices across major diseases and actors in homes, clinics, communities, hospitals and laboratories in South Africa. We conducted 101 semi-structured interviews and 7 focus group discussions with doctors, nurses, community health workers, patients, laboratory technicians, policymakers, hospital managers and manufacturers between September 2012 and June 2013 in Durban, Cape Town and Eastern Cape. The topics explored included diagnostic processes and challenges, understanding of diagnosis, and visions of ideal tests. For this paper, the data on HIV testing processes in clinics, communities and hospitals was used. RESULTS: Strategies to make HIV testing work at point of care involve overcoming constraints in equipment, spaces, human resources and workload and actively managing diagnostic processes. We grouped these strategies into subthemes: maintaining relationships, adapting testing guidelines and practices to stock-outs, to physical space, and to different clients, turning the test into a tool to reach another aim and turning the testing process into a tool to enhance adherence. These adaptive strategies are locally negotiated solutions, often ad-hoc, depending on personal commitment, relationships, human resources, physical space and referral systems. In the process, testing is redefined and repurposed. Not all of these repurposing acts are successful in ensuring a timely diagnosis. Some lead to disruptions, unnecessary testing or delays with at times unclear implications for quality of diagnosis. CONCLUSION: Tests shape relationships, professional roles and practices of users at point of care. At the same time, testing processes are dynamic and test results and processes take on new meanings for clients and providers. These insights are crucial for understanding the contexts within which diagnostic devices and policies need to function.

Improving the Quality of Diagnostic Studies Evaluating Point of Care Tests for Acute HIV Infections: Problems and Recommendations.

The diagnosis of acute human immunodeficiency virus (HIV) infection (AHI) plays a unique role in preventing the spread of HIV and ending the epidemic. Acutely infected individuals are thought to contribute substantially to forward transmissions of HIV; however, diagnosing AHI in resource-limited settings has proven to be a challenge. While fourth generation antigen-antibody combination assays have been successful in high-resource settings, rapid point of care (POC) versions of these assays have yet to demonstrate high sensitivity to detect AHI. Newer RNA/DNA based POC technologies are being validated, but the challenge to understand the additional value of these devices depends on the quality of study evaluations, in particular choice of study designs and case mix of included populations. In this commentary, we aimed to review the quality of studies evaluating a new fourth generation rapid test for detecting AHI, to identify general methodological limitations and biases in diagnostic accuracy studies, and to recommend strategies for avoiding them in future evaluations. The new studies that were evaluated continued to report the same weaknesses and biases that were seen in previous evaluations of fourth generation rapid tests. We recommend that investigators design future studies carefully, keeping in mind how diagnostic performance may be influenced by prevalence, population, patient case mixes, and reference standards. Care must be taken to avoid biases specific to diagnostic accuracy studies (spectrum, verification, incorporation and reference standard biases). To improve on quality, reporting checklists and guidelines such as Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Standards for Reporting Diagnostic accuracy studies (STARD) should be reviewed prior to conducting studies.

Measures and Metrics for Feasibility of Proof-of-Concept Studies With Human Immunodeficiency Virus Rapid Point-of-Care Technologies: The Evidence and the Framework.

OBJECTIVE: Pilot (feasibility) studies form a vast majority of diagnostic studies with point-of-care technologies but often lack use of clear measures/metrics and a consistent framework for reporting and evaluation. To fill this gap, we systematically reviewed data to (a) catalog feasibility measures/metrics and (b) propose a framework. METHODS: For the period January 2000 to March 2014, 2 reviewers searched 4 databases (MEDLINE, EMBASE, CINAHL, Scopus), retrieved 1441 citations, and abstracted data from 81 studies. We observed 2 major categories of measures, that is, implementation centered and patient centered, and 4 subcategories of measures, that is, feasibility, acceptability, preference, and patient experience. We defined and delineated metrics and measures for a feasibility framework. We documented impact measures for a comparison. FINDINGS: We observed heterogeneity in reporting of metrics as well as misclassification and misuse of metrics within measures. Although we observed poorly defined measures and metrics for feasibility, preference, and patient experience, in contrast, acceptability measure was the best defined. For example, within feasibility, metrics such as consent, completion, new infection, linkage rates, and turnaround times were misclassified and reported. Similarly, patient experience was variously reported as test convenience, comfort, pain, and/or satisfaction. In contrast, within impact measures, all the metrics were well documented, thus serving as a good baseline comparator. With our framework, we classified, delineated, and defined quantitative measures and metrics for feasibility. CONCLUSIONS: Our framework, with its defined measures/metrics, could reduce misclassification and improve the overall quality of reporting for monitoring and evaluation of rapid point-of-care technology strategies and their context-driven optimization.