How point-of-care testing could drive innovation in global health

The investment in health services in low- and middle-income countries has increased substantially in recent years.1 Such investment has been led by unprecedented efforts to combat major diseases, enabled by the availability of lower-cost and effective drug regimens for treatment and prophylaxis, along with improved vector control. As health services have expanded, so has the demand for diagnostic tests that are essential in identifying patients, determining prognosis, monitoring treatment, and assessing the efficacy of prevention.

Implementing SARS-CoV-2 antigen testing scale-up in Rwanda: retrospective analysis of national programme data and qualitative findings.

OBJECTIVES: Reverse transcriptase PCR is the most sensitive test for SARS-CoV-2 diagnosis. However, the scale-up of these tests in low-income and middle-income countries (LMICs) has been limited due to infrastructure and cost. Antigen rapid diagnostic tests are an alternative option for diagnosing active infection that may allow for faster, easier, less expensive and more widespread testing. We compared the implementation of antigen and PCR testing programmes in Rwanda. DESIGN: We retrospectively reviewed routinely collected PCR and antigen testing data for all reported tests conducted nationally. We administered semiquantitative surveys to healthcare workers (HCWs) involved in COVID-19 testing and care and clients receiving antigen testing. SETTING: Rwanda, November 2020-July 2021. PARTICIPANTS: National SARS-CoV-2 testing data; 49 HCWs involved in COVID-19 testing and care; 145 clients receiving antigen testing. INTERVENTIONS: None (retrospective analysis of programme data). PRIMARY AND SECONDARY OUTCOME MEASURES: Test volumes, turnaround times, feasibility and acceptability of antigen testing. RESULTS: Data from 906 204 antigen tests and 445 235 PCR tests were included. Antigen testing increased test availability and case identification compared with PCR and had a median results return time of 0 days (IQR: 0-0). In contrast, PCR testing time ranged from 1 to 18 days depending on the sample collection site/district. Both HCWs and clients indicated that antigen testing was feasible and acceptable. Some HCWs identified stockouts and limited healthcare staff as challenges. CONCLUSIONS: Antigen testing facilitated rapid expansion and decentralisation of SARS-CoV-2 testing across lower tier facilities in Rwanda, contributed to increased case identification, reduced test processing times, and was determined to be feasible and acceptable to clients and providers. Antigen testing will be an essential component of SARS-CoV-2 test and treat programmes in LMICs.

Building Integrated Testing Programs for Infectious Diseases.

In the past 2 decades, testing services for diseases such as human immunodeficiency virus (HIV), tuberculosis, and malaria have expanded dramatically. Investments in testing capacity and supportive health systems have often been disease specific, resulting in siloed testing programs with suboptimal capacity, reduced efficiency, and limited ability to introduce additional tests or respond to new outbreaks. Emergency demand for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing overcame these silos and demonstrated the feasibility of integrated testing. Moving forward, an integrated public laboratory infrastructure that services multiple diseases, including SARS-CoV-2, influenza, HIV, tuberculosis, hepatitis, malaria, sexually transmitted diseases, and other infections, will help improve universal healthcare delivery and pandemic preparedness. However, integrated testing faces many barriers including poorly aligned health systems, funding, and policies. Strategies to overcome these include greater implementation of policies that support multidisease testing and treatment systems, diagnostic network optimization, bundled test procurement, and more rapid spread of innovation and best practices across disease programs.

Human papillomavirus testing using existing nucleic acid testing platforms to screen women for cervical cancer: implementation studies from five sub-Saharan African countries.

OBJECTIVES: To demonstrate acceptability and operational feasibility of introducing human papillomavirus (HPV) testing as a principal cervical cancer screening method in public health programmes in sub-Saharan Africa. SETTING: 45 primary and secondary health clinics in Malawi, Nigeria, Senegal, Uganda and Zimbabwe. PARTICIPANTS: 15 766 women aged 25-54 years presenting at outpatient departments (Senegal only, general population) or at antiretroviral therapy clinics (all other countries, HIV-positive women only). Eligibility criteria followed national guidelines for cervical cancer screening. INTERVENTIONS: HPV testing was offered to eligible women as a primary screening for cervical cancer, and HPV-positive women were referred for visual inspection with acetic acid (VIA), and if lesions identified, received treatment or referral. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the proportion of HPV-positive women who received results and linked to VIA and the proportion of HPV-positive and VIA-positive women who received treatment. RESULTS: A total of 15 766 women were screened and tested for HPV, among whom 14 564 (92%) had valid results and 4710/14 564 (32%) were HPV positive. 13 837 (95%) of valid results were returned to the clinic and 3376 (72%) of HPV-positive women received results. Of women receiving VIA (n=2735), 715 (26%) were VIA-positive and 622 (87%) received treatment, 75% on the same day as VIA. CONCLUSIONS: HPV testing was found to be feasible across the five study countries in a public health setting, although attrition was seen at several key points in the cascade of care, namely results return to women and linkage to VIA. Once women received VIA, if eligible, the availability of on-site cryotherapy and thermal ablation allowed for same-day treatment. With sufficient resources and supportive infrastructure to ensure linkage to treatment, use of HPV testing for cervical cancer screening as recommended by WHO is a promising model in low-income and middle-income countries.

The performance of using dried blood spot specimens for HIV-1 viral load testing: A systematic review and meta-analysis.

BACKGROUND: Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While the use of plasma specimens is the standard for viral load testing, its use is restricted by the limited ambient temperature stability of viral load biomarkers in whole blood and plasma during storage and transportation and the limited cold chain available between many health care facilities in resource-limited settings. Alternative specimen types and technologies, such as dried blood spots, may address these issues and increase access to viral load testing; however, their technical performance is unclear. To address this, we conducted a meta-analysis comparing viral load results from paired dried blood spot and plasma specimens analyzed with commonly used viral load testing technologies. METHODS AND FINDINGS: Standard databases, conferences, and gray literature were searched in 2013 and 2018. Nearly all studies identified (60) were conducted between 2007 and 2018. Data from 40 of the 60 studies were included in the meta-analysis, which accounted for a total of 10,871 paired dried blood spot:plasma data points. We used random effects models to determine the bias, accuracy, precision, and misclassification for each viral load technology and to account for between-study variation. Dried blood spot specimens produced consistently higher mean viral loads across all technologies when compared to plasma specimens. However, when used to identify treatment failure, each technology compared best to plasma at a threshold of 1,000 copies/ml, the present World Health Organization recommended treatment failure threshold. Some heterogeneity existed between technologies; however, 5 technologies had a sensitivity greater than 95%. Furthermore, 5 technologies had a specificity greater than 85% yet 2 technologies had a specificity less than 60% using a treatment failure threshold of 1,000 copies/ml. The study's main limitation was the direct applicability of findings as nearly all studies to date used dried blood spot samples prepared in laboratories using precision pipetting that resulted in consistent input volumes. CONCLUSIONS: This analysis provides evidence to support the implementation and scale-up of dried blood spot specimens for viral load testing using the same 1,000 copies/ml treatment failure threshold as used with plasma specimens. This may support improved access to viral load testing in resource-limited settings lacking the required infrastructure and cold chain storage for testing with plasma specimens.

HIV viral load assays when used with whole blood perform well as a diagnostic assay for infants.

OBJECTIVE: Over the past several years, only approximately 50% of HIV-exposed infants received an early infant diagnosis test within the first two months of life. While high attrition and mortality account for some of the shortcomings in identifying HIV-infected infants early and putting them on life-saving treatment, fragmented and challenging laboratory systems are an added barrier. We sought to determine the accuracy of using HIV viral load assays for infant diagnosis of HIV. METHODS: We enrolled 866 Ugandan infants between March-April 2018 for this study after initial laboratory diagnosis. The median age was seven months, while 33% of infants were less than three months of age. Study testing was done using either the Roche or Abbott molecular technologies at the Central Public Health Laboratory. Dried blood spot samples were prepared according to manufacturer-recommended protocols for both the qualitative and quantitative assays. Viral load test samples for the Roche assay were processed using two different buffers: phosphate-buffered saline (PBS: free virus elution viral load protocol [FVE]) and Sample Pre-Extraction Reagent (SPEX: qualitative buffer). Dried blood spot samples were processed for both assays on the Abbott using the manufacturer's standard infant diagnosis protocol. All infants received a qualitative test for clinical management and additional paired quantitative tests. RESULTS: 858 infants were included in the analysis, of which 50% were female. Over 75% of mothers received antiretroviral therapy, while approximately 65% of infants received infant prophylaxis. The Roche SPEX and Abbott technologies had high sensitivity (>95%) and specificity (>98%). The Roche FVE had lower sensitivity (85%) and viral load values. CONCLUSIONS: To simplify and streamline laboratory practices, HIV viral load may be used to diagnose HIV infection in infants, particularly using the Roche SPEX and Abbott technologies.

Nucleic Acid Point-of-Care Testing to Improve Diagnostic Preparedness.

Testing programs for severe acute respiratory syndrome coronavirus 2 have relied on high-throughput polymerase chain reaction laboratory tests and rapid antigen assays to meet diagnostic needs. Both technologies are essential; however, issues of cost, accessibility, manufacturing delays, and performance have limited their use in low-resource settings and contributed to the global inequity in coronavirus disease 2019 testing. Emerging low-cost, multidisease point-of-care nucleic acid tests may address these limitations and strengthen pandemic preparedness, especially within primary healthcare where most cases of disease first present. Widespread deployment of these novel technologies will also help close long-standing test access gaps for other diseases, including tuberculosis, human immunodeficiency virus, cervical cancer, viral hepatitis, and sexually transmitted infections. We propose a more optimized testing framework based on greater use of point-of-care nucleic acid tests together with rapid immunologic assays and high-throughput laboratory molecular tests to improve the diagnosis of priority endemic and epidemic diseases, as well as strengthen the overall delivery of primary healthcare services.

Near-point-of-care viral load testing during pregnancy and viremia at delivery.

OBJECTIVES: Assess whether near-point-of-care (POC) viral load testing at the first antenatal care visit (ANC1) increased the proportion of women taking antiretroviral therapy who were virally suppressed at delivery through expedited clinical action. DESIGN: Difference-in-difference analysis. METHODS: At 20 public sector facilities in Zimbabwe, 10 implemented near-POC viral load testing at ANC1 (August 2019 to November 2020) and 10 used centralized viral load testing at ANC1. Study endpoints included time to result received, clinical action, and unsuppressed viral load (UVL; >1000 copies/ml) at delivery. RESULTS: Of 1782 women, only 46% came for ANC1 before their third trimester. Preimplementation, 28% of women received viral load testing at ANC1, increasing to 86% during implementation. In the near-POC viral load arm, women were more likely to receive their result within 30 days of ANC1 sample collection compared with the centralized laboratory arm [54 versus 14%, relative risk (RR): 4.17, 95% confidence interval (CI) 1.82-9.55], as well as receive clinical action among those with UVL (63 versus 8%, RR 7.88; 95% CI 1.53-40.47). However, we did not observe significant changes in risk of UVL at delivery with near-POC viral load (RR 1.02, 95% CI 0.95-1.10). CONCLUSION: ANC1 viral load coverage was initially low. Near-POC viral load testing at ANC1 dramatically improved the timeliness of result receipt by patients and clinical action for those with an UVL. Although we did not observe a significant impact of provision of near-POC viral load at ANC1 on re-suppression at delivery, potentially because of late presentation for ANC1, continued near-POC viral load testing during pregnancy and delivery may reduce UVL and mother-to-child transmission risk.

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.

Feasibility and impact of near-point-of-care integrated tuberculosis/HIV testing in Malawi and Zimbabwe.

OBJECTIVES: Near-point-of-care (POC) testing for early infant diagnosis (EID) and viral load expedites clinical action and improves outcomes but requires capital investment. We assessed whether excess capacity on existing near-POC devices used for TB diagnosis could be leveraged to increase near-POC HIV molecular testing, termed integrated testing, without compromising TB services. DESIGN: Preimplementation/postimplementation studies in 10 health facilities in Malawi and 8 in Zimbabwe. METHODS: Timeliness of EID and viral load test results and clinical action were compared between centralized and near-POC testing using Somers' D tests (continuous indicators) and risk ratios (RR, binary indicators); TB testing/treatment rates and timeliness were analyzed preintegration/postintegration. RESULTS: With integration, average device utilization increased but did not exceed 55%. Despite the addition of HIV testing, TB test volumes, timeliness, and treatment initiations were maintained. Although few HIV-positive infants were identified, near-POC EID testing improved treatment initiation within 1 month by 57% compared with centralized EID [Malawi RR: 1.57, 95% confidence interval (CI) 0.98-2.52], and near-POC viral load testing significantly increased the proportion of patients with elevated viral load receiving clinical action within 1 month (Zimbabwe RR: 5.26, 95% CI 3.38-8.20; Malawi RR: 3.90, 95% CI 2.58-5.91). CONCLUSION: Integrating TB/HIV testing using existing multidisease platforms is feasible and enables increased access to rapid diagnostics without disrupting existing TB services. Our results serve as an example of a novel, efficient implementation model that can increase access to critical testing services across disease silos and should be considered for additional clinical applications.

Point-of-care testing can achieve same-day diagnosis for infants and rapid ART initiation: results from government programmes across six African countries.

INTRODUCTION: Point-of-care (POC) early infant diagnosis (EID) testing has been shown to dramatically decrease turnaround times from sample collection to caregiver result receipt and time to ART initiation for HIV-positive infants compared to centralized laboratory testing. As governments in sub-Saharan Africa implement POC EID technologies, we report on the feasibility and effectiveness of POC EID testing and the impact of same-day result delivery on rapid ART initiation within national programmes across six countries. METHODS: This pre-/post-evaluation compared centralized laboratory-based (pre) with POC (post) EID testing in 52 facilities across Cameroon, Democratic Republic of Congo, Ethiopia, Kenya, Senegal and Zimbabwe between April 2017 and October 2019 (country-dependent). Data were collected retrospectively from routine records at health facilities for all infants tested under two years of age. Hazard ratios and 95% confidence intervals were calculated to compare time-to-event outcomes, visualized with Kaplan-Meier curves, and the Somers' D test was used to compare continuous outcomes. RESULTS: Data were collected for 2892 EID tests conducted on centralized laboratory-based platforms and 4610 EID tests on POC devices with 127 (4%) and 192 (4%) HIV-positive infants identified, respectively. POC EID significantly reduced the time from sample collection to caregiver result receipt (POC median: 0 days, IQR: 0 to 0 vs. centralized: 35 days, IQR: 26 to 56) and time from sample collection to ART initiation for HIV-positive infants (POC median: 1 day, IQR: 0 to 7 vs. centralized: 39 days, IQR: 26 to 57). With POC testing, 72% of infants received results on the same day as sample collection; HIV-positive infants with a same-day diagnosis had six times the rate of ART initiation compared to those diagnosed one or more days after sample collection (HR: 6.39; 95% CI: 3.44 to 11.85). CONCLUSIONS: Same-day diagnosis and treatment initiation for infants is possible with POC EID within routine government-led and -supported public sector healthcare facilities in resource-limited settings. Given that POC EID allows for rapid ART initiation, aligning to the World Health Organization's recommendation of ART initiation within seven days, its use in public sector programmes has the potential to reduce overall mortality for infants with HIV through early treatment initiation.

Evaluation of near point-of-care viral load implementation in public health facilities across seven countries in sub-Saharan Africa.

INTRODUCTION: In many low- and middle-income countries, HIV viral load (VL) testing occurs at centralized laboratories and time-to-result-delivery is lengthy, preventing timely monitoring of HIV treatment adherence. Near point-of-care (POC) devices, which are placed within health facility laboratories rather than clinics themselves (i.e. "true" POC), can offer VL in conjunction with centralized laboratories to expedite clinical decision making and improve outcomes, especially for patients at high risk of treatment failure. We assessed impacts of near-POC VL testing on result receipt and clinical action in public sector programmes in Cameroon, Democratic Republic of Congo, Kenya, Malawi, Senegal, Tanzania and Zimbabwe. METHODS: Routine health data were collected retrospectively after introducing near-POC VL testing at 57 public sector health facilities (2017 to 2019, country-dependent). Where possible, key indicators were compared to data from patients receiving centralized laboratory testing using hazard ratios and the Somers' D test. RESULTS: Data were collected from 6795 tests conducted on near-POC and 17614 tests on centralized laboratory-based platforms. Thirty-one percent (2062/6694) of near-POC tests were conducted for high-risk populations: pregnant and breastfeeding women, children and those with suspected failure. Compared to conventional testing, near-POC improved the median time from sample collection to return of results to patient [six vs. sixty-eight days, effect size: -32.2%; 95% CI: -41.0% to -23.4%] and to clinical action for individuals with an elevated HIV VL [three vs. fourty-nine days, effect size: -35.4%; 95% CI: -46.0% to -24.8%]. Near-POC VL results were two times more likely to be returned to the patient within 90 days compared to centralized tests [50% (1781/3594) vs. 27% (4172/15271); aHR: 2.22, 95% CI: 2.05 to 2.39]. Thirty-seven percent (340/925) of patients with an elevated near-POC HIV VL result had documented clinical follow-up actions within 30 days compared to 7% (167/2276) for centralized testing. CONCLUSIONS: Near-POC VL testing enabled rapid test result delivery for high-risk populations and led to significant improvements in the timeliness of patient result receipt compared to centralized testing. While there was some improvement in time-to-clinical action with near-POC VL testing, major gaps remained. Strengthening of systems supporting the utilization of results for patient management are needed to truly capitalize on the benefits of decentralized testing.

Modern diagnostic technologies for HIV.

Novel diagnostic technologies, including nanotechnology, microfluidics, -omics science, next-generation sequencing, genomics big data, and machine learning, could contribute to meeting the UNAIDS 95-95-95 targets to end the HIV epidemic by 2030. Novel technologies include multiplexed technologies (including biomarker-based point-of-care tests and molecular platform technologies), biomarker-based combination antibody and antigen technologies, dried-blood-spot testing, and self-testing. Although biomarker-based rapid tests, in particular antibody-based tests, have dominated HIV diagnostics since the development of the first HIV test in the mid-1980s, targets such as nucleic acids and genes are now used in nanomedicine, biosensors, microfluidics, and -omics to enable early diagnosis of HIV. These novel technologies show promise as they are associated with ease of use, high diagnostic accuracy, rapid detection, and the ability to detect HIV-specific markers. Additional clinical and implementation research is needed to generate evidence for use of novel technologies and a public health approach will be required to address clinical and operational challenges to optimise their global deployment.

Building and Sustaining Optimized Diagnostic Networks to Scale-up HIV Viral Load and Early Infant Diagnosis.

BACKGROUND: Progress toward meeting the UNAIDS 2014 HIV treatment (90-90-90) targets has been slow in some countries because of gaps in access to HIV diagnostic tests. Emerging point-of-care (POC) molecular diagnostic technologies for HIV viral load (VL) and early infant diagnosis (EID) may help reduce diagnostic gaps. However, these technologies need to be implemented in a complementary and strategic manner with laboratory-based instruments to ensure optimization. METHOD: Between May 2019 and February 2020, a systemic literature search was conducted in PubMed, the Cochrane Library, MEDLINE, conference abstracts, and other sources such as Unitaid, UNAIDS, WHO, and UNICEF websites to determine factors that would affect VL and EID scale-up. Data relevant to the search themes were reviewed for accuracy and were included. RESULTS: Collaborations among countries, implementing partners, and donors have identified a set of framework for the effective use of both POC-based and laboratory-based technologies in large-scale VL and EID testing programs. These frameworks include (1) updated testing policies on the operational utility of POC and laboratory-based technologies, (2) expanded integrated testing using multidisease diagnostic platforms, (3) laboratory network mapping, (4) use of more efficient procurement and supply chain approaches such as all-inclusive pricing and reagent rental, and (5) addressing systemic issues such as test turnaround time, sample referral, data management, and quality systems. CONCLUSIONS: Achieving and sustaining optimal VL and EID scale-up within tiered diagnostic networks would require better coordination among the ministries of health of countries, donors, implementing partners, diagnostic manufacturers, and strong national laboratory and clinical technical working groups.

Proportions of CD4 test results indicating advanced HIV disease remain consistently high at primary health care facilities across four high HIV burden countries.

BACKGROUND: Globally, nearly 22 million HIV-infected patients are currently accessing antiretroviral treatment; however, almost one million people living with HIV died of AIDS-related illnesses in 2018. Advanced HIV disease remains a significant issue to curb HIV-related mortality. METHODS: We analyzed 864,389 CD4 testing records collected by 1,016 Alere Pima Analyzers implemented at a variety of facilities, including peripheral facilities, between January 2012 and December 2016 across four countries in sub-Saharan Africa. Routinely collected data and programmatic records were used to analyze the median CD4 counts and proportions of patients with advanced HIV disease by country, facility type, and year. RESULTS: Median CD4 counts were between 409-444 cells/ul each year since 2012 with a median in 2016 of 444 cells/ul (n = 319,829). The proportion of test results returning CD4 counts above 500 cells/ul has increased slowly each year with 41.8% (95% CI: 41.6-41.9%) of tests having a CD4 count above 500 cells/ul in 2016. Median CD4 counts were similar across facility types. The proportion of test results indicating advanced HIV disease has remained fairly consistent: 19.4% (95% CI: 18.8-20.1%) in 2012 compared to 16.1% (95% CI: 16.0-16.3%) in 2016. The proportion of test results indicating advanced HIV disease annually ranged from 14.5% in Uganda to 29.8% in Cameroon. 6.9% (95% CI: 6.8-7.0%) of test results showed very advanced HIV disease (CD4<100 cells/ul) in 2016. CONCLUSIONS: The proportion of CD4 test results indicating advanced disease was relatively high and consistent across four high HIV burden countries.

Point-of-care CD4 technology invalid result rates in public health care settings across five countries.

BACKGROUND: Since 2010, point-of-care (POC) CD4 testing platforms have been introduced in both urban and rural settings to expand access to testing by bringing diagnostic services closer to patients. We conducted an analysis of routinely collected CD4 testing data to determine the invalid result rates associated with POC CD4 testing. METHODS: We analyzed 981,152 CD4 testing records collected from Alere Pima Analyzers between January 2011 and December 2016 across five countries in sub-Saharan Africa. Routinely collected data and programmatic records were used to determine the rate of invalid test results per month, by facility type, and by operator based on cumulative usage during the study period. In addition, frequency of invalid test types and utilization of control beads were assessed. RESULTS: Across the five countries, 75,530 invalid messages were returned, resulting in an overall invalid result rate of 7.7%. The invalid result rate by country ranged from 6.6% to 11.2%. Invalid result rates were consistent across facility types. Invalid result rates were inversely correlated with operator usage: low volume operators (<50 tests over study period) experienced an invalid result rate of 10.2%, while high volume operators (>500 tests over study period) experienced an invalid result rate of 5.5%. Two invalid result types (exposure position control and reagent control) accounted for nearly 50% of invalid results. Routine data showed that control beads were run on 88.3% of days that the device was used. CONCLUSIONS: Our analysis found that the rate of invalid results was consistent across all types of health facilities, indicating that decentralization of POC CD4 testing to lower level health facilities did not exhibit high invalid result rates or increase cartridge wastage. Additionally, invalid result rates were inversely correlated to operator usage, with high-volume operators experiencing lower invalid result rates than low-volume operators. POC CD4 testing can, therefore, be performed in decentralized national testing programs; however, adequate training, quality assurance, routine monitoring, and ongoing mentorship should also be implemented for success.

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.

Performance of Cepheid Xpert HIV-1 viral load plasma assay to accurately detect treatment failure.

BACKGROUND: Coverage of viral load testing remains low with only half of the patients in need having adequate access. Alternative technologies to high throughput centralized machines can be used to support viral load scale-up; however, clinical performance data are lacking. We conducted a meta-analysis comparing the Cepheid Xpert HIV-1 viral load plasma assay to traditional laboratory-based technologies. METHODS: Cepheid Xpert HIV-1 and comparator laboratory technology plasma viral load results were provided from 13 of the 19 eligible studies, which accounted for a total of 3790 paired data points. We used random effects models to determine the accuracy and misclassification at various treatment failure thresholds (detectable, 200, 400, 500, 600, 800 and 1000 copies/ml). RESULTS: Thirty percent of viral load test results were undetectable, while 45% were between detectable and 10 000 copies/ml and the remaining 25% were above 10 000 copies/ml. The median Xpert viral load was 119 copies/ml and the median comparator viral load was 157 copies/ml, while the log10 bias was 0.04 (0.02-0.07). The sensitivity and specificity to detect treatment failure were above 95% at all treatment failure thresholds, except for detectable, at which the sensitivity was 93.33% (95% confidence interval: 88.2-96.3) and specificity was 80.56% (95% CI: 64.6-90.4). CONCLUSION: The Cepheid Xpert HIV-1 viral load plasma assay results were highly comparable to laboratory-based technologies with limited bias and high sensitivity and specificity to detect treatment failure. Alternative specimen types and technologies that enable decentralized testing services can be considered to expand access to viral load.