Blood-based colorectal cancer screening in an integrated health system: a randomised trial of patient adherence.

OBJECTIVE: We evaluated whether people who had not completed a faecal immunochemical test (FIT) for colorectal cancer (CRC) screening would complete a blood-based testing option if offered one during health encounters. Blood-based screening tests for CRC could add to the total number of people screened for CRC by providing another testing alternative. DESIGN: Study participants were patients aged 45-75 years at a large, integrated health system who were offered but did not complete an FIT in the prior 3-9 months and were scheduled for a clinical encounter. Individuals were randomised (1:1) to be offered a commercially available CRC blood test (Shield, Guardant Health) versus usual care. We compared 3-month CRC screening proportions in the two groups. RESULTS: We randomised 2026 patients; 2004 remained eligible following postrandomisation exclusions (1003 to usual care and 1001 to blood draw offer; mean age: 60, 62% female, 80% non-Hispanic white). Of the 1001 allocated to the blood test group, 924 were recruited following chart-review exclusions; 548 (59.3%) were reached via phone, of which 280 (51.1%) scheduled an appointment with the research team. CRC screening proportions were 17.5 percentage points higher in the blood test group versus usual care (30.5% vs 13.0%; OR 2.94, 95% CI 2.34 to 3.70; p<0.001). CONCLUSION: Among adults who had declined prior CRC screening, the offer of a blood-based screening test boosted CRC screening by 17.5 percentage points over usual care. Further research is needed on how to balance the favourable adherence with lower advanced adenoma detection compared with other available tests. TRIAL REGISTRATION NUMBER: NCT05987709.

Clinical accuracy of instrument-based SARS-CoV-2 antigen diagnostic tests: a systematic review and meta-analysis.

BACKGROUND: During the COVID-19 pandemic, antigen diagnostic tests were frequently used for screening, triage, and diagnosis. Novel instrument-based antigen tests (iAg tests) hold the promise of outperforming their instrument-free, visually-read counterparts. Here, we provide a systematic review and meta-analysis of the SARS-CoV-2 iAg tests' clinical accuracy. METHODS: We systematically searched MEDLINE (via PubMed), Web of Science, medRxiv, and bioRxiv for articles published before November 7th, 2022, evaluating the accuracy of iAg tests for SARS-CoV-2 detection. We performed a random effects meta-analysis to estimate sensitivity and specificity and used the QUADAS-2 tool to assess study quality and risk of bias. Sub-group analysis was conducted based on Ct value range, IFU-conformity, age, symptom presence and duration, and the variant of concern. RESULTS: We screened the titles and abstracts of 20,431 articles and included 114 publications that fulfilled the inclusion criteria. Additionally, we incorporated three articles sourced from the FIND website, totaling 117 studies encompassing 95,181 individuals, which evaluated the clinical accuracy of 24 commercial COVID-19 iAg tests. The studies varied in risk of bias but showed high applicability. Of 24 iAg tests from 99 studies assessed in the meta-analysis, the pooled sensitivity and specificity compared to molecular testing of a paired NP swab sample were 76.7% (95% CI 73.5 to 79.7) and 98.4% (95% CI 98.0 to 98.7), respectively. Higher sensitivity was noted in individuals with high viral load (99.6% [95% CI 96.8 to 100] at Ct-level ≤ 20) and within the first week of symptom onset (84.6% [95% CI 78.2 to 89.3]), but did not differ between tests conducted as per manufacturer's instructions and those conducted differently, or between point-of-care and lab-based testing. CONCLUSION: Overall, iAg tests have a high pooled specificity but a moderate pooled sensitivity, according to our analysis. The pooled sensitivity increases with lower Ct-values (a proxy for viral load), or within the first week of symptom onset, enabling reliable identification of most COVID-19 cases and highlighting the importance of context in test selection. The study underscores the need for careful evaluation considering performance variations and operational features of iAg tests.

Accuracy of and preferences for blood-based versus oral-fluid-based HIV self-testing in Malawi: a cross-sectional study.

BACKGROUND: HIV self-testing (HIVST) can use either oral-fluid or blood-based tests. Studies have shown strong preferences for self-testing compared to facility-based services. Despite availability of low-cost blood-based HIVST options, to date, HIVST implementation in sub-Saharan Africa has largely been oral-fluid-based. We investigated whether users preferred blood-based (i.e. using blood sample derived from a finger prick) or oral fluid-based HIVST in rural and urban Malawi. METHODS: At clinics providing HIV testing services (n = 2 urban; n = 2 rural), participants completed a semi-structured questionnaire capturing sociodemographic data before choosing to test using oral-fluid-based HVST, blood-based HIVST or provider-delivered testing. They also completed a self-administered questionnaire afterwards, followed by a confirmatory test using the national algorithm then appropriate referral. We used simple and multivariable logistic regression to identify factors associated with preference for oral-fluid or blood-based HIVST. RESULTS: July to October 2018, N = 691 participants enrolled in this study. Given the choice, 98.4% (680/691) selected HIVST over provider-delivered testing. Of 680 opting for HIVST, 416 (61.2%) chose oral-fluid-based HIVST, 264 (38.8%) chose blood-based HIVST and 99.1% (674/680) reported their results appropriately. Self-testers who opted for blood-based HIVST were more likely to be male (50.3% men vs. 29.6% women, p < 0.001), attending an urban facility (43% urban vs. 34.6% rural, p = 0.025) and regular salary-earners (49.5% regular vs. 36.8% non-regular, p = 0.012). After adjustment, only sex was found to be associated with choice of self-test (adjusted OR 0.43 (95%CI: 0.3-0.61); p-value < 0.001). Among 264 reporting blood-based HIVST results, 11 (4.2%) were HIV-positive. Blood-based HIVST had sensitivity of 100% (95% CI: 71.5-100%) and specificity of 99.6% (95% CI: 97.6-100%), with 20 (7.6%) invalid results. Among 416 reporting oral-fluid-based HIVST results 18 (4.3%) were HIV-positive. Oral-fluid-based HIVST had sensitivity of 88.9% (95% CI: 65.3-98.6%) and specificity of 98.7% (95% CI: 97.1-99.6%), with no invalid results. CONCLUSIONS: Offering both blood-based and oral-fluid-based HIVST resulted in high uptake when compared directly with provider-delivered testing. Both types of self-testing achieved high accuracy among users provided with a pre-test demonstration beforehand. Policymakers and donors need to adequately plan and budget for the sensitisation and support needed to optimise the introduction of new quality-assured blood-based HIVST products.

Costs of distributing HIV self-testing kits in Eswatini through community and workplace models.

BACKGROUND: This study evaluates the implementation and running costs of an HIV self-testing (HIVST) distribution program in Eswatini. HIVST kits were delivered through community-based and workplace models using primary and secondary distribution. Primary clients could self-test onsite or offsite. This study presents total running economic costs of kit distribution per model between April 2019 and March 2020, and estimates average cost per HIVST kit distributed, per client self-tested, per client self-tested reactive, per client confirmed positive, and per client initiating antiretroviral therapy (ART). METHODS: Distribution data and follow-up phone interviews were analysed to estimate implementation outcomes. Results were presented for each step of the care cascade using best-case and worst-case scenarios. A top-down incremental cost-analysis was conducted from the provider perspective using project expenditures. Sensitivity and scenario analyses explored effects of economic and epidemiological parameters on average costs. RESULTS: Nineteen thousand one hundred fifty-five HIVST kits were distributed to 13,031 individuals over a 12-month period, averaging 1.5 kits per recipient. 83% and 17% of kits were distributed via the community and workplace models, respectively. Clients reached via the workplace model were less likely to opt for onsite testing than clients in the community model (8% vs 29%). 6% of onsite workplace testers tested reactive compared to 2% of onsite community testers. Best-case scenario estimated 17,458 (91%) clients self-tested, 633 (4%) received reactive-test results, 606 (96%) linked to confirmatory testing, and 505 (83%) initiated ART. Personnel and HIVST kits represented 60% and 32% of total costs, respectively. Average costs were: per kit distributed US$17.23, per client tested US$18.91, per client with a reactive test US$521.54, per client confirmed positive US$550.83, and per client initiating ART US$708.60. Lower rates for testing, reactivity, and linkage to care in the worst-case scenario resulted in higher average costs along the treatment cascade. CONCLUSION: This study fills a significant evidence gap regarding costs of HIVST provision along the client care cascade in Eswatini. Workplace and community-based distribution of HIVST accompanied with effective linkage to care strategies can support countries to reach cascade objectives.

Experience of social harms among female sex workers following HIV self-test distribution in Malawi: results of a cohort study.

BACKGROUND: In Malawi, female sex workers (FSW) have high HIV incidence and regular testing is suggested. HIV self-testing (HIVST) is a safe and acceptable alternative to standard testing services. This study assessed; whether social harms were more likely to be reported after HIVST distribution to FSW by peer distributors than after facility-based HIV testing and whether FSW regretted HIVST use or experienced associated relationship problems. METHODS: Peer HIVST distributors, who were FSW, were recruited in Blantyre district, Malawi between February and July 2017. Among HIVST recipients a prospective cohort was recruited. Interviews were conducted at baseline and at end-line, 3 months later. Participants completed daily sexual activity diaries. End-line data were analysed using logistic regression to assess whether regret or relationship problems were associated with HIVST use. Sexual activity data were analysed using Generalised Estimating Equations to assess whether HIVST use was temporally associated with an increase in social harms. RESULTS: Of 265 FSW recruited and offered HIVST, 131 completed both interviews. Of these, 31/131(23.7%) reported initial regret after HIVST use, this reduced to 23/131(17.6%) at the 3-month follow-up. Relationship problems were reported by 12/131(9.2%). Regret about HIVST use was less commonly reported in those aged 26-35 years compared to those aged 16-25 years (OR immediate regret-0.40 95% CI 0.16-1.01) (OR current regret-0.22 95% CI 0.07 - 0.71) and was not associated with the HIVST result. There was limited evidence that reports of verbal abuse perpetrated by clients in the week following HIVST use were greater than when there was no testing in the preceding week. There was no evidence for increases in any other social harms. There was some evidence of coercion to test, most commonly initiated by the peer distributor. CONCLUSIONS: Little evidence was found that the peer distribution model was associated with increased levels of social harms, however programmes aimed at reaching FSW need to carefully consider possible unintended consequences of their service delivery approaches, including the potential for peer distributors to coerce individuals to test or disclose their test results and alternative distribution models may need to be considered.

Lessons learned from implementation of four HIV self-testing (HIVST) distribution models in Zambia: applying the Consolidated Framework for Implementation Research to understand impact of contextual factors on implementation.

BACKGROUND: Although Zambia has integrated HIV-self-testing (HIVST) into its Human Immunodeficiency Virus (HIV) regulatory frameworks, few best practices to optimize the use of HIV self-testing to increase testing coverage have been documented. We conducted a prospective case study to understand contextual factors guiding implementation of four HIVST distribution models to inform scale-up in Zambia. METHODS: We used the qualitative case study method to explore user and provider experiences with four HIVST distribution models (two secondary distribution models in Antenatal Care (ANC) and Antiretroviral Therapy (ART) clinics, community-led, and workplace) to understand factors influencing HIVST distribution. Participants were purposefully selected based on their participation in HIVST and on their ability to provide rich contextual experience of the distribution models. Data were collected using observations (n = 31), group discussions (n = 10), and in-depth interviews (n = 77). Data were analyzed using the thematic approach and aligned to the four Consolidated Framework for Implementation Research (CFIR) domains. RESULTS: Implementation of the four distribution models was influenced by an interplay of outer and inner setting factors. Inadequate compensation and incentives for distributors may have contributed to distributor attrition in the community-led and workplace HIVST models. Stockouts, experienced at the start of implementation in the secondary-distribution and community-led distribution models often disrupted distribution. The existence of policy and practices aided integration of HIVST in the workplace. External factors complimented internal factors for successful implementation. For instance, despite distributor attrition leading to excessive workload, distributors often multi-tasked to keep up with demand for kits, even though distribution points were geographically widespread in the workplace, and to a less extent in the community-led models. Use of existing communication platforms such as lunchtime and safety meetings to promote and distribute kits, peers to support distributors, reduction in trips by distributors to replenish stocks, increase in monetary incentives and reorganisation of stakeholder roles proved to be good adaptations. CONCLUSION: HIVST distribution was influenced by a combination of contextual factors in variable ways. Understanding how the factors interacted in real world settings informed adaptations to implementation devised to minimize disruptions to distribution.

A typology of HIV self-testing support systems: a scoping review.

To maximise the benefits of HIV self-testing (HIVST), it is critical to support self-testers in the testing process and ensure that they access appropriate prevention and care. To summarise systems and tools supporting HIVST (hereafter, 'support systems') and categorise them for future analysis, we synthesised the global data on HIVST support systems and proposed a typology. We searched five databases for articles reporting on one or more HIVST support systems and included 314 publications from 224 studies. Across 189 studies, there were 539 reports of systems supporting HIVST use; while across 115 studies, there were 171 reports of systems supporting result interpretation. Most commonly, these were pictorial instructions, followed by in-person demonstrations and in-person assistance while self-testing or reading self-test results. Less commonly, virtual interventions were also identified, including online video conferencing and smartphone apps. Smartphone-based automated result readers have been used in the USA, China, and South Africa. Across 173 studies, there were 987 reports of systems supporting post-test linkage to care; most commonly, these were in-person referrals/counselling, written referrals, and phone helplines. In the USA, Bluetooth beacons have been trialled to monitor self-test use and facilitate follow-up. We found that, globally, HIVST support systems use a range of methods, including static media, virtual tools, and in-person engagement. In-person and printed approaches were more common than virtual tools. Other considerations, such as linguistic and cultural appropriateness, may also be important in the development of effective HIVST programs.

The future of HIV testing in eastern and southern Africa: Broader scope, targeted services.

In this Policy Forum, Anna Grimsrud and colleagues discuss the future of HIV testing in eastern and southern Africa, using insights gleaned from a 2021 expert consultation.

Demand creation for HIV testing services: A systematic review and meta-analysis.

BACKGROUND: HIV testing services (HTS) are the first steps in reaching the UNAIDS 95-95-95 goals to achieve and maintain low HIV incidence. Evaluating the effectiveness of different demand creation interventions to increase uptake of efficient and effective HTS is useful to prioritize limited programmatic resources. This review was undertaken to inform World Health Organization (WHO) 2019 HIV testing guidelines and assessed the research question, "Which demand creation strategies are effective for enhancing uptake of HTS?" focused on populations globally. METHODS AND FINDINGS: The following electronic databases were searched through September 28, 2021: PubMed, PsycInfo, Cochrane CENTRAL, CINAHL Complete, Web of Science Core Collection, EMBASE, and Global Health Database; we searched IAS and AIDS conferences. We systematically searched for randomized controlled trials (RCTs) that compared any demand creation intervention (incentives, mobilization, counseling, tailoring, and digital interventions) to either a control or other demand creation intervention and reported HTS uptake. We pooled trials to evaluate categories of demand creation interventions using random-effects models for meta-analysis and assessed study quality with Cochrane's risk of bias 1 tool. This study was funded by the WHO and registered in Prospero with ID CRD42022296947. We screened 10,583 records and 507 conference abstracts, reviewed 952 full texts, and included 124 RCTs for data extraction. The majority of studies were from the African (N = 53) and Americas (N = 54) regions. We found that mobilization (relative risk [RR]: 2.01, 95% confidence interval [CI]: [1.30, 3.09], p < 0.05; risk difference [RD]: 0.29, 95% CI [0.16, 0.43], p < 0.05, N = 4 RCTs), couple-oriented counseling (RR: 1.98, 95% CI [1.02, 3.86], p < 0.05; RD: 0.12, 95% CI [0.03, 0.21], p < 0.05, N = 4 RCTs), peer-led interventions (RR: 1.57, 95% CI [1.15, 2.15], p < 0.05; RD: 0.18, 95% CI [0.06, 0.31], p < 0.05, N = 10 RCTs), motivation-oriented counseling (RR: 1.53, 95% CI [1.07, 2.20], p < 0.05; RD: 0.17, 95% CI [0.00, 0.34], p < 0.05, N = 4 RCTs), short message service (SMS) (RR: 1.53, 95% CI [1.09, 2.16], p < 0.05; RD: 0.11, 95% CI [0.03, 0.19], p < 0.05, N = 5 RCTs), and conditional fixed value incentives (RR: 1.52, 95% CI [1.21, 1.91], p < 0.05; RD: 0.15, 95% CI [0.07, 0.22], p < 0.05, N = 11 RCTs) all significantly and importantly (≥50% relative increase) increased HTS uptake and had medium risk of bias. Lottery-based incentives and audio-based interventions less importantly (25% to 49% increase) but not significantly increased HTS uptake (medium risk of bias). Personal invitation letters and personalized message content significantly but not importantly (<25% increase) increased HTS uptake (medium risk of bias). Reduced duration counseling had comparable performance to standard duration counseling (low risk of bias) and video-based interventions were comparable or better than in-person counseling (medium risk of bias). Heterogeneity of effect among pooled studies was high. This study was limited in that we restricted to randomized trials, which may be systematically less readily available for key populations; additionally, we compare only pooled estimates for interventions with multiple studies rather than single study estimates, and there was evidence of publication bias for several interventions. CONCLUSIONS: Mobilization, couple- and motivation-oriented counseling, peer-led interventions, conditional fixed value incentives, and SMS are high-impact demand creation interventions and should be prioritized for programmatic consideration. Reduced duration counseling and video-based interventions are an efficient and effective alternative to address staffing shortages. Investment in demand creation activities should prioritize those with undiagnosed HIV or ongoing HIV exposure. Selection of demand creation interventions must consider risks and benefits, context-specific factors, feasibility and sustainability, country ownership, and universal health coverage across disease areas.

Climate-informed forecasts reveal dramatic local habitat shifts and population uncertainty for northern boreal caribou.

Most research on boreal populations of woodland caribou (Rangifer tarandus caribou) has been conducted in areas of high anthropogenic disturbance. However, a large portion of the species' range overlaps relatively pristine areas primarily affected by natural disturbances, such as wildfire. Climate-driven habitat change is a key concern for the conservation of boreal-dependent species, where management decisions have yet to consider knowledge from multiple ecological domains integrated into a cohesive and spatially explicit forecast of species-specific habitat and demography. We used a novel ecological forecasting framework to provide climate-sensitive projections of habitat and demography for five boreal caribou monitoring areas within the Northwest Territories (NWT), Canada, over 90 years. Importantly, we quantify uncertainty around forecasted mean values. Our results suggest habitat suitability may increase in central and southwest regions of the NWT's Taiga Plains ecozone but decrease in southern and northwestern regions driven by conversion of coniferous to deciduous forests. We do not project that boreal caribou population growth rates will change despite forecasted changes to habitat suitability. Our results emphasize the importance of efforts to protect and restore northern boreal caribou habitat despite climate uncertainty while highlighting expected spatial variations that are important considerations for local people who rely on them. An ability to reproduce previous work, and critical thought when incorporating sources of uncertainty, will be important to refine forecasts, derive management decisions, and improve conservation efficacy for northern species at risk.

The Future of Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: A Global Qualitative Consultation on Provider Perspectives on New Products and Differentiated Service Delivery.

Differentiated service delivery and new products, such as long-acting injectable cabotegravir (CAB-LA) and the dapivirine vaginal ring (DVR), could increase uptake and use of pre-exposure prophylaxis (PrEP) for HIV prevention. We explored PrEP provider perspectives on differentiated PrEP service delivery and new PrEP products to inform World Health Organization (WHO) guidelines and programme implementation. 150 PrEP providers who participated in a WHO survey were randomly selected and 67 were invited for interviews based on geographic representation, provider cadre, gender, experience with community-based PrEP service delivery, and familiarity with new PrEP products. Semi-structured interviews were conducted virtually. Key themes were inductively extracted relating to differentiated service delivery and benefits and concerns regarding new PrEP products. 30 PrEP providers from 24 countries were interviewed. Across regions, providers were supportive of differentiated service delivery to respond to clients' needs and preferences, maintain services during COVID-19, and ensure access for priority populations that may face access challenges. Providers welcomed prospects of offering CAB-LA to their clients but had concerns about HIV testing, costs, and the need for clinic-based services, including staff who can administer injections. Providers felt the DVR was potentially important for some cisgender women, especially young clients and female sex workers, and raised fewer concerns compared to injectable PrEP. Providers' views are critical for the development of guidelines and implementing programmes that will best serve PrEP users. Understanding areas where provider capacities and biases may create barriers can define opportunities for training and support to ensure that providers can deliver effective programmes.

Secondary distribution of HIV self-test kits by HIV index and antenatal care clients: implementation and costing results from the STAR Initiative in South Africa.

BACKGROUND: Partner-delivered HIV self-testing kits has previously been highlighted as a safe, acceptable and effective approach to reach men. However, less is known about its real-world implementation in reaching partners of people living with HIV. We evaluated programmatic implementation of partner-delivered self-testing through antenatal care (ANC) attendees and people newly diagnosed with HIV by assessing use, positivity, linkage and cost per kit distributed. METHODS: Between April 2018 and December 2019, antenatal care (ANC) clinic attendees and people or those newly diagnosed with HIV clients across twelve clinics in three cities in South Africa were given HIVST kits (OraQuick Rapid HIV-1/2 Antibody Test, OraSure Technologies) to distribute to their sexual partners. A follow-up telephonic survey was administered to all prior consenting clients who were successfully reached by telephone to assess primary outcomes. Incremental economic costs of the implementation were estimated from the provider's perspective. RESULTS: Fourteen thousand four hundred seventy-three HIVST kits were distributed - 10,319 (71%) to ANC clients for their male partner and 29% to people newly diagnosed with HIV for their partners. Of the 4,235 ANC clients successfully followed-up, 82.1% (3,475) reportedly offered HIVST kits to their male partner with 98.1% (3,409) accepting and 97.6% (3,328) using the kit. Among ANC partners self-testing, 159 (4.8%) reported reactive HIVST results, of which 127 (79.9%) received further testing; 116 (91.3%) were diagnosed with HIV and 114 (98.3%) initiated antiretroviral therapy (ART). Of the 1,649 people newly diagnosed with HIV successfully followed-up; 1,312 (79.6%) reportedly offered HIVST kits to their partners with 95.8% (1,257) of the partners accepting and 95.9% (1,206) reported that their partners used the kit. Among these index partners, 297 (24.6%) reported reactive HIVST results of which 261 (87.9%) received further testing; 260 (99.6%) were diagnosed with HIV and 258 (99.2%) initiated ART. The average cost per HIVST distributed in the three cities was US$7.90, US$11.98, and US$14.81, respectively. CONCLUSIONS: Partner-delivered HIVST in real world implementation was able to affordably reach many male partners of ANC attendees and index partners of people newly diagnosed with HIV in South Africa. Given recent COVID-19 related restrictions, partner-delivered HIVST provides an important strategy to maintain essential testing services.

Do community measures impact the effectiveness of a community led HIV testing intervention. Secondary analysis of an HIV self-testing intervention in rural communities in Zimbabwe.

BACKGROUND: There is a growing body of evidence for the role that communities can have in producing beneficial health outcomes. There is also an increasing recognition of the effectiveness and success of community-led interventions to promote public health efforts. This study investigated whether and how community-level measures facilitate a community-led intervention to achieve improved HIV outcomes. METHODS: This is a secondary analysis of survey data from a cluster randomised trial in 40 rural communities in Zimbabwe. The survey was conducted four months after the intervention was initiated. Communities were randomised 1:1 to either paid distribution arm, where HIV self-test (HIVST) kits were distributed by a paid distributor, or community-led whereby members of the community were responsible for organising and conducting the distribution of HIVST kits. We used mixed effects logistic regression to assess the effect of social cohesion, problem solving, and HIV awareness on HIV testing and prevention. RESULTS: We found no association between community measures and the three HIV outcomes (self-testing, new HIV diagnosis and linkage to VMMC or confirmatory testing). However, the interaction analyses highlighted that in high social cohesion communities, the odds of new HIV diagnosis was greater in the community-led arm than paid distribution arm (OR 2.06 95% CI 1.03-4.19). CONCLUSION: We found some evidence that community-led interventions reached more undiagnosed people living with HIV in places with high social cohesion. Additional research should seek to understand whether the effect of social cohesion is persistent across other community interventions and outcomes. TRIAL REGISTRATION: PACTR201607001701788.

Improved rapid diagnostic tests to detect syphilis and yaws: a systematic review and meta-analysis.

BACKGROUND: Current rapid tests for syphilis and yaws can detect treponemal and non-treponemal antibodies. We aimed to critically appraise the literature for rapid diagnostic tests (RDTs) which can better distinguish an active infection of syphilis or yaws. METHODS: We conducted a systematic review and meta-analysis, searching five databases between January 2010 and October 2021 (with an update in July 2022). A generalised linear mixed model was used to conduct a bivariate meta-analysis for the pooled sensitivity and specificity. Heterogeneity was assessed using the I2 statistic. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) to assess the risk of bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) to evaluate the certainty of evidence. RESULTS: We included 17 studies for meta-analyses. For syphilis, the pooled sensitivity and specificity of the treponemal component were 0.93 (95% CI: 0.86 to 0.97) and 0.98 (95% CI: 0.96 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.90 (95% CI: 0.82 to 0.95) and 0.97 (95% CI: 0.92 to 0.99), respectively. For yaws, the pooled sensitivity and specificity of the treponemal component were 0.86 (95% CI: 0.66 to 0.95) and 0.97 (95% CI: 0.94 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.80 (95% CI: 0.55 to 0.93) and 0.96 (95% CI: 0.92 to 0.98), respectively. CONCLUSIONS: RDTs that can differentiate between active and previously treated infections could optimise management by providing same-day treatment and reducing unnecessary treatment. PROSPERO REGISTRATION NUMBER: CRD42021279587.

Examining the Use of HIV Self-Testing to Support PrEP Delivery: a Systematic Literature Review.

PURPOSE OF REVIEW: HIV self-testing (HIVST) has the potential to expand access to and uptake of HIV pre-exposure prophylaxis (PrEP) delivery. We conducted a systematic literature review to understand the evidence on HIVST use for PrEP delivery. RECENT FINDINGS: After screening 1055 records, we included eight: three randomized trials and five values and preferences studies. None measured PrEP initiation. Most studies occurred in Sub-Saharan Africa (7/8) and included different populations. One trial found that HIVST use between quarterly clinic visits as part of an adherence package with biofeedback slightly increased adherence; the other two trials found that HIVST use between or in lieu of quarterly clinic visits had no significant or non-inferior effects on adherence. HIVST to support PrEP delivery was acceptable, feasible, and preferred. HIVST use for PrEP continuation largely resulted in similar outcomes to standard-of-care delivery and was perceived acceptable and feasible. Further research is needed to optimize HIVST use within PrEP programming.

HIV Testing Uptake According to Opt-In, Opt-Out or Risk-Based Testing Approaches: a Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Improving HIV testing uptake is essential to ending the HIV pandemic. HIV testing approaches can be opt-in, opt-out or risk-based. This systematic review examines and compares the uptake of HIV testing in opt-in, opt-out and risk-based testing approaches. RECENT FINDINGS: There remain missed opportunities for HIV testing in a variety of settings using different approaches: opt-in (a person actively accepts to be tested for HIV), opt-out (a person is informed that HIV testing is routine/standard of care, and they actively decline if they do not wish to be tested for HIV) or risk-based (using risk-based screening tools to focus testing on certain individuals or sub-populations at greater risk of HIV). It is not clear how the approach could impact HIV test uptake when adjusted for other factors (e.g. rapid testing, country-income level, test setting and population tested). We searched four databases for studies reporting on HIV test uptake. In total, 18,238 records were screened, and 150 studies were included in the review. Most studies described an opt-in approach (87 estimates), followed by opt-out (76) and risk-based (19). Opt-out testing was associated with 64.3% test uptake (I2 = 99.9%), opt-in testing with 59.8% (I2 = 99.9%) and risk-based testing with 54.4% (I2 = 99.9%). When adjusted for settings that offered rapid testing, country income level, setting and population tested, opt-out testing had a significantly higher uptake (+ 12% (95% confidence intervals: 3-21), p = 0.007) than opt-in testing. We also found that emergency department patients and hospital outpatients had significantly lower HIV test uptake than other populations.

Did you hear about HIV self-testing? HIV self-testing awareness after community-based HIVST distribution in rural Zimbabwe.

BACKGROUND: Several trials of community-based HIV self-testing (HIVST) provide evidence on the acceptability and feasibility of campaign-style distribution to reach first-time testers, men and adolescents. However, we do not know how many remain unaware of HIVST after distribution campaigns, and who these individuals are. Here we look at factors associated with never having heard of HIVST after community-based campaign-style HIVST distribution in rural Zimbabwe between September 2016 and July 2017. METHODS: Analysis of representative population-based trial survey data collected from 7146 individuals following community-based HIVST distribution to households was conducted. Factors associated with having never heard of HIVST were determined using multivariable mixed-effects logistic regression adjusted for clustered design. RESULTS: Among survey participants, 1308 (18.3%) self-reported having never heard of HIVST. Individuals who were between 20 and 60 years old {20-29 years: [aOR = 0.74, 95% CI (0.58-0.95)], 30-39 years: [aOR = 0.56, 95% CI (0.42-0.74)], 40-49 years: [aOR = 0.50, 95% CI (0.36-0.68)], 50-59 years [aOR = 0.58, 95% CI (0.42-0.82)]}, who had attained at least ordinary level education [aOR = 0.51, 95% CI (0.34-0.76)], and who had an HIV test before [aOR = 0.30, 95% CI (0.25-0.37)] were less likely to have never heard of HIVST compared with individuals who were between 16 and 19 years old, who had a lower educational level and who had never tested for HIV before, respectively. In addition, non-household heads or household head representatives [aOR = 1.21, 95% CI (1.01-1.45)] were more likely to report never having heard of HIVST compared to household head and representatives. CONCLUSIONS: Around one fifth of survey participants remain unaware of HIVST even after an intensive community-based door-to-door HIVST distribution. Of note, those least likely to have heard of self-testing were younger, less educated and less likely to have tested previously. Household heads appear to play an important role in granting or denying access to self-testing to other household members during door-to-door distribution. Differentiated distribution models are needed to ensure access to all. Trial registration PACTR, PACTR201607001701788. Registered 29 June 2016, https://pactr.samrc.ac.za/ PACTR201607001701788.

"You have a self-testing method that preserves privacy so how come you cannot give us treatment that does too?" Exploring the reasoning among young people about linkage to prevention, care and treatment after HIV self-testing in Southern Malawi.

BACKGROUND: Young people, aged 16-24, in southern Malawi have high uptake of HIV self-testing (HIVST) but low rates of linking to services following HIVST, especially in comparison, to older generations. The study aim is to explore the barriers and facilitators to linkage for HIV prevention and care following uptake of HIV self-testing among young Malawians. METHODS: We used qualitative methods. Young people aged 16-24 who had received HIVST; community-based distribution agents (CBDAs) and health care workers from the linked facilities were purposively sampled from two villages in rural southern Malawi. RESULTS: We conducted in-depth interviews with thirteen young people (9 female) and held four focus groups with 28 healthcare workers and CBDAs. Young people strongly felt the social consequences associated with inadvertent disclosure of HIV sero-status were a significant deterrent to linkage at their stage in life. They also felt communication on testing benefits and the referral process after testing was poor. In contrast, they valued encouragement from those they trusted, other's positive treatment experiences and having a "strength of mind". CBDAs were important facilitators for young people as they are able to foster a trusting relationship and had more understanding of the factors which prevented young people from linking following HIVST than the healthcare workers. Young people noted contextual barriers to linkage, for example, being seen on the road to the healthcare centre, but also societal gendered barriers. For example, young females and younger adolescents were less likely to have the financial independence to link to services whilst young males (aged 19-24) had the finances but lacked a supportive network to encourage linkage following testing. Overall, it was felt that the primary "responsibility" for linking to formal healthcare following self-testing is shouldered by the young person and not the healthcare system. CONCLUSIONS: Young people are happy to self-test for HIV but faced barriers to link to services following a self-test. Potential interventions for improving linkage suggested by this analysis include the establishment of youth-friendly linkage services, enhanced lines of communication between young people and healthcare providers and prioritising linkage for future interventions when targeting young people following HIVST.

Usability and acceptability of oral-based HCV self-testing among key populations: a mixed-methods evaluation in Tbilisi, Georgia.

BACKGROUND: Hepatitis C virus self-testing (HCVST) is an additional approach that may expand access to HCV testing. We conducted a mixed-methods cross-sectional observational study to assess the usability and acceptability of HCVST among people who inject drugs (PWID), men who have sex with men (MSM) and transgender (TG) people in Tbilisi, Georgia. METHODS: The study was conducted from December 2019 to June 2020 among PWID at one harm reduction site and among MSM/TG at one community-based organization. We used a convergent parallel mixed-methods design. Usability was assessed by observing errors made and difficulties faced by participants. Acceptability was assessed using an interviewer-administered semi-structured questionnaire. A subset of participants participated in cognitive and in-depth interviews. RESULTS: A total of 90 PWID, 84 MSM and 6 TG were observed performing HCVST. PWID were older (median age 35 vs 24) and had a lower level of education compared to MSM/TG (27% vs 59%). The proportion of participants who completed all steps successfully without assistance was 60% among PWID and 80% among MSM/TG. The most common error was in sample collection and this was observed more often among PWID than MSM/TG (21% vs 6%; p = 0.002). More PWID requested assistance during HCVST compared to MSM/TG (22% vs 8%; p = 0.011). Acceptability was high in both groups (98% vs 96%; p = 0.407). Inter-reader agreement was 97% among PWID and 99% among MSM/TG. Qualitative data from cognitive (n = 20) and in-depth interviews (n = 20) was consistent with the quantitative data confirming a high usability and acceptability. CONCLUSIONS: HCVST was highly acceptable among key populations in Georgia of relatively high educational level, and most participants performed HCVST correctly. A significant difference in usability was observed among PWID compared to MSM/TG, indicating that PWID may benefit from improved messaging and education as well as options to receive direct assistance when self-testing for HCV.

Sensitivity and specificity of OraQuick® HIV self-test compared to a 4th generation laboratory reference standard algorithm in urban and rural Zambia.

BACKGROUND: HIV self-testing (HIVST) has the potential to increase coverage of HIV testing, but concerns exist about intended users' ability to correctly perform and interpret tests, especially in poor communities with low literacy rates. We assessed the clinical performance of the 2016 prototype OraQuick® HIV Self-Test in rural and urban communities in Zambia to assess the sensitivity and specificity of the test compared to the national HIV rapid diagnostic test (RDT) algorithm and a laboratory reference standard using 4th generation enzyme immunoassays and HIV RNA detection. METHODS: Participants were recruited from randomly selected rural and urban households and one urban health facility between May 2016 and June 2017. Participants received a brief demonstration of the self-test, and then self-tested without further assistance. The research team re-read the self-test, repeated the self-test, drew blood for the laboratory reference, and conducted RDTs following the national HIV testing algorithm (Determine™ HIV1/2 (Alere) confirmed using Unigold™ HIV1/2 (Trinity Biotech)). Selected participants (N = 85) were videotaped whilst conducting the testing to observe common errors. RESULTS: Initial piloting showed that written instructions alone were inadequate, and a demonstration of self-test use was required. Of 2,566 self-test users, 2,557 (99.6%) were able to interpret their result. Of participants who were videoed 75/84 (89.3%) completed all steps of the procedure correctly. Agreement between the user-read result and the researcher-read result was 99.1%. Compared to the RDT algorithm, user-conducted HIVST was 94.1% sensitive (95%CI: 90.2-96.7) and 99.7% specific (95%CI: 99.3-99.9). Compared to the laboratory reference, both user-conducted HIVST (sensitivity 87.5%, 95%CI: 82.70-91.3; specificity 99.7%, 95%CI: 99.4-99.9) and the national RDT algorithm (sensitivity 93.4%, 95%CI: 89.7-96.1%; specificity 100% (95%CI: 99.8-100%) had considerably lower sensitivity. CONCLUSIONS: Self-testers in Zambia who used OraQuick® HIV Self-Test achieved reasonable clinical performance compared to the national RDT algorithm. However, sensitivity of the self-test was reduced compared to a laboratory reference standard, as was the national RDT algorithm. In-person demonstration, along with the written manufacturer instructions, was needed to obtain accurate results. Programmes introducing self-care diagnostics should pilot and optimise support materials to ensure they are appropriately adapted to context.