Impact of HIV self-testing for oral pre-exposure prophylaxis scale-up on drug resistance and HIV outcomes in western Kenya: a modelling study.

BACKGROUND: Community-based oral pre-exposure prophylaxis (PrEP) provision has the potential to expand PrEP coverage. HIV self-testing can facilitate PrEP community-based delivery but might have lower sensitivity than facility-based HIV testing, potentially leading to inappropriate PrEP use among people with HIV and subsequent development of drug resistance. We aimed to evaluate the impact of HIV self-testing use for PrEP scale-up. METHODS: We parameterised an agent-based network model, EMOD-HIV, to simulate generic tenofovir disoproxil fumarate and emtricitabine PrEP scale-up in western Kenya using four testing scenarios: provider-administered nucleic acid testing, provider-administered rapid diagnostic tests detecting antibodies, blood-based HIV self-testing, or oral fluid HIV self-testing. Scenarios were compared with a no PrEP counterfactual. Individuals aged 18-49 years with one or more heterosexual partners who screened HIV-negative were eligible for PrEP. We assessed the cost and health impact of rapid PrEP scale-up with high coverage over 20 years, and the budget impact over 5 years, using various HIV testing modalities. FINDINGS: PrEP coverage of 29% was projected to avert approximately 54% of HIV infections and 17% of HIV-related deaths among adults aged 18-49 years over 20 years; health impacts were similar across HIV testing modalities used to deliver PrEP. The percentage of HIV infections with PrEP-associated nucleoside reverse transcriptase inhibitor (NRTI) drug resistance was 0·6% (95% uncertainty intervals 0·4-0·9) in the blood HIV self-testing scenario and 0·8% (0·6-1·0) in the oral HIV self-testing scenario, compared with 0·3% (0·2-0·3) in the antibody rapid diagnostic testing scenario and 0·2% (0·1-0·2) in the nucleic acid testing scenario. Accounting for background NRTI resistance, we found similarly low proportions of drug resistance across scenarios. The budget impact of implementing PrEP using HIV self-testing and provider-administered rapid diagnostic tests were similar, while nucleic acid testing was approximately 50% more costly. INTERPRETATION: Scaling up PrEP using HIV self-testing has similar health impacts, costs, and low risk of drug resistance as provider-administered rapid diagnostic tests. Policy makers should consider leveraging HIV self-testing to expand PrEP access among those at HIV risk. FUNDING: The Bill and Melinda Gates Foundation.

Country adoption of WHO 2019 guidance on HIV testing strategies and algorithms: a policy review across the WHO African region.

OBJECTIVES: In 2019, the WHO released guidelines on HIV testing service (HTS). We aim to assess the adoption of six of these recommendations on HIV testing strategies among African countries. DESIGN: Policy review. SETTING: 47 countries within the WHO African region. PARTICIPANTS: National HTS policies from the WHO African region as of December 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: Uptake of WHO recommendations across national HTS policies including the standard three-test strategy; discontinuation of a tiebreaker test to rule in HIV infection; discontinuation of western blotting (WB) for HIV diagnosis; retesting prior to antiretroviral treatment (ART) initiation and the use of dual HIV/syphilis rapid diagnostic tests (RDTs) in antenatal care. Country policy adoption was assessed on a continuum, based on varying levels of complete adoption. RESULTS: National policies were reviewed for 96% (n=45/47) of countries in the WHO African region, 38% (n=18) were published before 2019 and 60% (n=28) adopted WHO guidance. Among countries that had not fully adopted WHO guidance, not yet adopting a three-test strategy was the most common reason for misalignment (45%, 21/47); of which 31% and 22% were in low-prevalence (<5%) and high-prevalence (≥5%) countries, respectively. Ten policies (21%) recommended the use of WB and 49% (n=23) recommended retesting before ART initiation. Dual HIV/syphilis RDTs were recommended in 45% (n=21/47) of policies. CONCLUSIONS: Many countries in the African region have adopted WHO-recommended HIV testing strategies; however, efforts are still needed to fully adopt WHO guidance. Countries should accelerate their efforts to adopt and implement a three-test strategy, retesting prior to ART initiation and the use of dual HIV/syphilis RDTs.

Country adherence to WHO recommendations to improve the quality of HIV diagnosis: a global policy review.

INTRODUCTION: Ensuring a correct and timely HIV diagnosis is critical. WHO publishes guidelines on HIV testing strategies that maximise the likelihood of correctly determining one's HIV status. A review of national HIV testing policies in 2014 found low adherence to WHO guidelines. We updated this review to determine adherence to current recommendations. METHODS: We conducted a comprehensive policy review through April 2018. We extracted data on HIV testing strategies, recommendations on HIV retesting prior to antiretroviral therapy (ART) initiation and pre-exposure prophylaxis (PrEP)-related HIV testing information. Descriptive analyses disaggregated by region were conducted to ascertain adherence to recommendations and to describe testing strategy characteristics. RESULTS: Of 91 policies included, 26% (n=24/91) adhered to WHO recommendations. Having a two-assay testing strategy to rule-in HIV infection as opposed to the recommended three-assay testing strategy was a major reason for non-adherence. Of 72 country policies providing sufficient information, 31% (n=22) recommended retesting for HIV prior to initiating ART. Of 25 countries and two regions reporting PrEP-related HIV testing guidelines, almost all recommended testing prior to initiating PrEP and every 3 months during PrEP use. CONCLUSIONS: Global adherence to WHO recommendations for HIV testing strategies have improved since 2014 but remain low. We found adherence existed on a continuum. Such a system provides insights into how countries can move towards adherence by making relatively minor changes to testing strategies. Guidance from WHO on the role of new HIV testing technologies within testing algorithms and identifying ways to simplify testing guidance is warranted.

Optimizing HIV testing services in sub-Saharan Africa: cost and performance of verification testing with HIV self-tests and tests for triage.

INTRODUCTION: Strategies employing a single rapid diagnostic test (RDT) such as HIV self-testing (HIVST) or "test for triage" (T4T) are proposed to increase HIV testing programme impact. Current guidelines recommend serial testing with two or three RDTs for HIV diagnosis, followed by retesting with the same algorithm to verify HIV-positive status before anti-retroviral therapy (ART) initiation. We investigated whether clients presenting to HIV testing services (HTS) following a single reactive RDT must undergo the diagnostic algorithm twice to diagnose and verify HIV-positive status, or whether a diagnosis with the setting-specific algorithm is adequate for ART initiation. METHODS: We calculated (1) expected number of false-positive (FP) misclassifications per 10,000 HIV negative persons tested, (2) positive predictive value (PPV) of the overall HIV testing strategy compared to the WHO recommended PPV ≥99%, and (3) expected cost per FP misclassified person identified by additional verification testing in a typical low-/middle-income setting, compared to the expected lifetime ART cost of $3000. Scenarios considered were as follows: 10% prevalence using two serial RDTs for diagnosis, 1% prevalence using three serial RDTs, and calibration using programmatic data from Malawi in 2017 where the proportion of people testing HIV positive in facilities was 4%. RESULTS: In the 10% HIV prevalence setting with a triage test, the expected number of FP misclassifications was 0.86 per 10,000 tested without verification testing and the PPV was 99.9%. In the 1% prevalence setting, expected FP misclassifications were 0.19 with 99.8% PPV, and in the Malawi 2017 calibrated setting the expected misclassifications were 0.08 with 99.98% PPV. The cost per FP identified by verification testing was $5879, $3770, and $24,259 respectively. Results were sensitive to assumptions about accuracy of self-reported reactive results and whether reactive triage test results influenced biased interpretation of subsequent RDT results by the HTS provider. CONCLUSIONS: Diagnosis with the full algorithm following presentation with a reactive triage test is expected to achieve PPV above the 99% threshold. Continuing verification testing prior to ART initiation remains recommended, but HIV testing strategies involving HIVST and T4T may provide opportunities to maintain quality while increasing efficiency as part of broader restructuring of HIV testing service delivery.

Laboratory evaluation of four HIV/syphilis rapid diagnostic tests.

BACKGROUND: Sexually transmitted infections, such as HIV and syphilis, are one of the major health care problems worldwide, especially in low- and middle income countries. HIV screening programmes have been widely used for many years. The introduction of rapid point-of-care tests (RDTs) that can detect both HIV and syphilis, using one single blood specimen, would be a promising tool to integrate the detection of syphilis into HIV programmes and so improve the accessibility of syphilis testing and treatment. METHODS: As part of the World Health Organization pre-qualification of in vitro diagnostics assessment, the laboratory performance of four dual HIV-Syphilis rapid diagnostic tests (SD Bioline HIV/Syphilis Duo, DPP HIV-Syphilis Assay, Multiplo Rapid TP/HIV Antibody Test and Insti Multiplex HIV-1/HIV-2/Syphilis Antibody Test) was assessed using a well characterized multiregional panel of stored sera specimens. RESULTS: In total 400 specimens were tested with each assay, resulting in excellent sensitivities and specificities for HIV, ranging from 99.5 to 100% and from 93.5 to 99.5%, respectively. Results obtained for the Treponema pallidum antibodies were lower, with the lowest sensitivity of 73.5% for Multiplo and the highest of 87% for SD Bioline. Specificities ranged from 99.0 to 100%. CONCLUSION: Although these results suggest that the tests could further improve in accuracy in detection of treponemal antibodies, their introduction into screening programmes to increase the accessibility of HIV/Syphilis diagnosis and treatment for difficult to reach populations in the world is promising.

Reliability of HIV rapid diagnostic tests for self-testing compared with testing by health-care workers: a systematic review and meta-analysis.

BACKGROUND: The ability of individuals to use HIV self-tests correctly is debated. To inform the 2016 WHO recommendation on HIV self-testing, we assessed the reliability and performance of HIV rapid diagnostic tests when used by self-testers. METHODS: In this systematic review and meta-analysis, we searched PubMed, PopLine, and Embase, conference abstracts, and additional grey literature between Jan 1, 1995, and April 30, 2016, for observational and experimental studies reporting on HIV self-testing performance. We excluded studies evaluating home specimen collection because patients did not interpret their own test results. We extracted data independently, using standardised extraction forms. Outcomes of interest were agreement between self-testers and health-care workers, sensitivity, and specificity. We calculated κ to establish the level of agreement and pooled κ estimates using a random-effects model, by approach (directly assisted or unassisted) and type of specimen (blood or oral fluid). We examined heterogeneity with the I2 statistic. FINDINGS: 25 studies met inclusion criteria (22 to 5662 participants). Quality assessment with QUADAS-2 showed studies had low risk of bias and incomplete reporting in accordance with the STARD checklist. Raw proportion of agreement ranged from 85·4% to 100%, and reported κ ranged from fair (κ 0·277, p<0·001) to almost perfect (κ 0·99, n=25). Pooled κ suggested almost perfect agreement for both types of approaches (directly assisted 0·98, 95% CI 0·96-0·99 and unassisted 0·97, 0·96-0·98; I2=34·5%, 0-97·8). Excluding two outliers, sensitivity and specificity was higher for blood-based rapid diagnostic tests (4/16) compared with oral fluid rapid diagnostic tests (13/16). The most common error that affected test performance was incorrect specimen collection (oral swab or finger prick). Study limitations included the use of different reference standards and no disaggregation of results by individuals taking antiretrovirals. INTERPRETATION: Self-testers can reliably and accurately do HIV rapid diagnostic tests, as compared with trained health-care workers. Errors in performance might be reduced through the improvement of rapid diagnostic tests for self-testing, particularly to make sample collection easier and to simplify instructions for use. FUNDING: The Bill & Melinda Gates Foundation and Unitaid.

One or two serological assay testing strategy for diagnosis of HBV and HCV infection? The use of predictive modelling.

BACKGROUND: Initial serological testing for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is conducted using either rapid diagnostic tests (RDT) or laboratory-based enzyme immunoassays (EIA)s for detection of hepatitis B surface antigen (HBsAg) or antibodies to HCV (anti-HCV), typically on serum or plasma specimens and, for certain RDTs, capillary whole blood. WHO recommends the use of standardized testing strategies - defined as a sequence of one or more assays to maximize testing accuracy while simplifying the testing process and ideally minimizing cost. Our objective was to examine the diagnostic outcomes of a one- versus two-assay serological testing strategy. These data were used to inform recommendations in the 2017 WHO Guidelines on hepatitis B and C testing. METHODS: Few published studies have compared diagnostic outcomes for one-assay versus two-assay serological testing strategies for HBsAg and anti-HCV. Therefore, the principles of Bayesian statistics were used to conduct a modelling exercise to examine the outcomes of a one-assay versus two-assay testing strategy when applied to a hypothetical population of 10,000 individuals. The resulting model examined the diagnostic outcomes (true and false positive diagnoses; true and false negative diagnoses; positive and negative predictive values as a function of prevalence; and total tests required) for both one-assay and two-assay testing strategies. The performance characteristics assumed for assays used within the testing strategies were informed by WHO prequalification assessment findings and systematic reviews for diagnostic accuracy studies. Each of the presumptive testing strategies (one-assay or two-assay) was modelled at varying prevalences of HBsAg (10%, 2% and 0.4%) and of anti-HCV (40%, 10%, 2% and 0.4%), aimed at representing the range of testing populations typically encountered in WHO Member States. When the two-assay testing strategy was considered, the model assumed the independence of the two assays. RESULTS: Modeling demonstrated that applying a single assay (HBsAg or anti-HCV), even with high specificity (99%), may result in considerable numbers of false positive diagnoses and low positive predictive values (PPV), particularly in lower prevalence settings. Even at very low prevalences shifting to a two-assay testing strategy would result in a PPV approaching 1.0. When test sensitivity is high (>99%) false negative reactions are rare at all but the highest prevalences; but a two-test strategy might yield more false negative diagnoses. The order in which the tests are used has no impact on the overall accuracy of a two-assay strategy though it may impact the total number of tests needed to complete the diagnostic strategy, incurring added cost and complexity. HBsAg assays may have a low sensitivity (<90%), and result in large numbers of false negative diagnoses, particularly in high prevalence settings, which would be exacerbated in the two-assay testing strategy. In contrast, most anti-HCV assays have high sensitivity and lead to fewer false negative results, both in the one-assay and two-assay testing strategies. At prevalences ≤2% the number of tests needed using a second assay was nearly always small, at <300 per 10,000 individuals tested, making sustainability of a second assay uncertain in such a setting. CONCLUSIONS: A key public health objective of an effective testing strategy is to identify all individuals who would benefit from treatment. Therefore, a strategy that prioritizes a high NPV (minimal false negatives) may be acceptable even if the PPV is suboptimal (some false positives) as the implementation of such a public health programme must also take account of other factors such as costs, feasibility, impact on testing uptake and linkage to care, and consequences of a false-positive test. This rationale informed the development of the WHO Viral Hepatitis Testing Guidelines, with a conditional recommendation for a one-assay serological testing strategy in most testing settings and populations (≥0.4% prevalence in population tested). A one-test strategy results in few failures to diagnose infection and, although it is associated under most assumptions with a sub-optimal PPV, benefits include greater simplicity, easier implementation, lower costs and better feasibility, uptake and linkage to care. Furthermore, prior to antiviral therapy all those diagnosed either HBsAg or anti-HCV positive will require confirmation of viræmia, preventing unnecessary treatment of those who may be false positive on serology. For HBsAg, in low-prevalence settings (≤0.4%), a second recommendation was made to consider a two-assay testing strategy, using a confirmatory neutralization step or a second different HBsAg assay.

The cost and cost-effectiveness of rapid testing strategies for yaws diagnosis and surveillance.

BACKGROUND: Yaws is a non-venereal treponemal infection caused by Treponema pallidum subspecies pertenue. The disease is targeted by WHO for eradication by 2020. Rapid diagnostic tests (RDTs) are envisaged for confirmation of clinical cases during treatment campaigns and for certification of the interruption of transmission. Yaws testing requires both treponemal (trep) and non-treponemal (non-trep) assays for diagnosis of current infection. We evaluate a sequential testing strategy (using a treponemal RDT before a trep/non-trep RDT) in terms of cost and cost-effectiveness, relative to a single-assay combined testing strategy (using the trep/non-trep RDT alone), for two use cases: individual diagnosis and community surveillance. METHODS: We use cohort decision analysis to examine the diagnostic and cost outcomes. We estimate cost and cost-effectiveness of the alternative testing strategies at different levels of prevalence of past/current infection and current infection under each use case. We take the perspective of the global yaws eradication programme. We calculate the total number of correct diagnoses for each strategy over a range of plausible prevalences. We employ probabilistic sensitivity analysis (PSA) to account for uncertainty and report 95% intervals. RESULTS: At current prices of the treponemal and trep/non-trep RDTs, the sequential strategy is cost-saving for individual diagnosis at prevalence of past/current infection less than 85% (81-90); it is cost-saving for surveillance at less than 100%. The threshold price of the trep/non-trep RDT (below which the sequential strategy would no longer be cost-saving) is US$ 1.08 (1.02-1.14) for individual diagnosis at high prevalence of past/current infection (51%) and US$ 0.54 (0.52-0.56) for community surveillance at low prevalence (15%). DISCUSSION: We find that the sequential strategy is cost-saving for both diagnosis and surveillance in most relevant settings. In the absence of evidence assessing relative performance (sensitivity and specificity), cost-effectiveness is uncertain. However, the conditions under which the combined test only strategy might be more cost-effective than the sequential strategy are limited. A cheaper trep/non-trep RDT is needed, costing no more than US$ 0.50-1.00, depending on the use case. Our results will help enhance the cost-effectiveness of yaws programmes in the 13 countries known to be currently endemic. It will also inform efforts in the much larger group of 71 countries with a history of yaws, many of which will have to undertake surveillance to confirm the interruption of transmission.

To err is human, to correct is public health: a systematic review examining poor quality testing and misdiagnosis of HIV status.

INTRODUCTION: In accordance with global testing and treatment targets, many countries are seeking ways to reach the "90-90-90" goals, starting with diagnosing 90% of all people with HIV. Quality HIV testing services are needed to enable people with HIV to be diagnosed and linked to treatment as early as possible. It is essential that opportunities to reach people with undiagnosed HIV are not missed, diagnoses are correct and HIV-negative individuals are not inadvertently initiated on life-long treatment. We conducted this systematic review to assess the magnitude of misdiagnosis and to describe poor HIV testing practices using rapid diagnostic tests. METHODS: We systematically searched peer-reviewed articles, abstracts and grey literature published from 1 January 1990 to 19 April 2017. Studies were included if they used at least two rapid diagnostic tests and reported on HIV misdiagnosis, factors related to potential misdiagnosis or described quality issues and errors related to HIV testing. RESULTS: Sixty-four studies were included in this review. A small proportion of false positive (median 3.1%, interquartile range (IQR): 0.4-5.2%) and false negative (median: 0.4%, IQR: 0-3.9%) diagnoses were identified. Suboptimal testing strategies were the most common factor in studies reporting misdiagnoses, particularly false positive diagnoses due to using a "tiebreaker" test to resolve discrepant test results. A substantial proportion of false negative diagnoses were related to retesting among people on antiretroviral therapy. Conclusions HIV testing errors and poor practices, particularly those resulting in false positive or false negative diagnoses, do occur but are preventable. Efforts to accelerate HIV diagnosis and linkage to treatment should be complemented by efforts to improve the quality of HIV testing services and strengthen the quality management systems, particularly the use of validated testing algorithms and strategies, retesting people diagnosed with HIV before initiating treatment and providing clear messages to people with HIV on treatment on the risk of a "false negative" test result.

Examining the effects of HIV self-testing compared to standard HIV testing services: a systematic review and meta-analysis.

INTRODUCTION: HIV self-testing (HIVST) is a discreet and convenient way to reach people with HIV who do not know their status, including many who may not otherwise test. To inform World Health Organization (WHO) guidance, we assessed the effect of HIVST on uptake and frequency of testing, as well as identification of HIV-positive persons, linkage to care, social harm, and risk behaviour. METHODS: We systematically searched for studies comparing HIVST to standard HIV testing until 1 June 2016. Meta-analyses of studies reporting comparable outcomes were conducted using a random-effects model for relative risks (RR) and 95% confidence intervals. The quality of evidence was evaluated using GRADE. RESULTS: After screening 638 citations, we identified five randomized controlled trials (RCTs) comparing HIVST to standard HIV testing services among 4,145 total participants from four countries. All offered free oral-fluid rapid tests for HIVST and were among men. Meta-analysis of three RCTs showed HIVST doubled uptake of testing among men (RR = 2.12; 95% CI: 1.51, 2.98). Meta-analysis of two RCTs among men who have sex with men showed frequency of testing nearly doubled (Rate ratio = 1.88; 95% CI: 1.17; 3.01), resulting in two more tests in a 12-15-month period (Mean difference = 2.13; 95% CI: 1.59, 2.66). Meta-analysis of two RCTs showed HIVST also doubled the likelihood of an HIV-positive diagnosis (RR = 2.02; 95% CI: 0.37, 10.76, 5.32). Across all RCTs, there was no indication of harm attributable to HIVST and potential increases in risk-taking behaviour appeared to be minimal. CONCLUSIONS: HIVST is associated with increased uptake and frequency of testing in RCTs. Such increases, particularly among those at risk who may not otherwise test, will likely identify more HIV-positive individuals as compared to standard testing services alone. However, further research on how to support linkage to confirmatory testing, prevention, treatment and care services is needed. WHO now recommends HIVST as an additional HIV testing approach.

Diagnosis of viral hepatitis.

PURPOSE OF REVIEW: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and HIV-HBV and HCV coinfection are major causes of chronic liver disease worldwide. Testing and diagnosis is the gateway for access to both treatment and prevention services, but there remains a large burden of undiagnosed infection globally. We review the global epidemiology, key challenges in the current hepatitis testing response, new tools to support the hepatitis global response (2016-2020 Global Hepatitis Health Sector strategy, and 2017 WHO guidelines on hepatitis testing) and future directions and innovations in hepatitis diagnostics. RECENT FINDINGS: Key challenges in the current hepatitis testing response include lack of quality-assured serological and low-cost virological in-vitro diagnostics, limited facilities for testing, inadequate data to guide country-specific hepatitis testing approaches, stigmatization of those with or at risk of viral hepatitis and lack of guidelines on hepatitis testing for resource-limited settings. The new Global Hepatitis Health Sector strategy sets out goals for elimination of viral hepatitis as a public health threat by 2030 and gives outcome targets for reductions in new infections and mortality, as well as service delivery targets that include testing, diagnosis and treatment. The 2017 WHO hepatitis testing guidelines for adults, adolescents and children in low-income and middle-income countries outline the public health approach to strengthen and expand current testing practices for viral hepatitis and addresses who to test (testing approaches), which serological and virological assays to use (testing strategies) as well as interventions to promote linkage to prevention and care. SUMMARY: Future directions and innovations in hepatitis testing include strategies to improve access such as through use of existing facility and community-based testing opportunities for hepatitis testing, near-patient or point-of-care assays for virological markers (nucleic acid testing and HCV core antigen), dried blood spot specimens used with different serological and nucleic acid test assays, multiplex and multi-disease platforms to enable testing for multiple analytes/pathogens and potential self-testing for viral hepatitis.

Can trained lay providers perform HIV testing services? A review of national HIV testing policies.

BACKGROUND: Only an estimated 54% of people living with HIV are aware of their status. Despite progress scaling up HIV testing services (HTS), a testing gap remains. Delivery of HTS by lay providers may help close this testing gap, while also increasing uptake and acceptability of HIV testing among key populations and other priority groups. METHODS: 50 National HIV testing policies were collated from WHO country intelligence databases, contacts and testing program websites. Data regarding lay provider use for HTS was extracted and collated. Our search had no geographical or language restrictions. This data was then compared with reported data from the Global AIDS Response Progress Reporting (GARPR) from July 2015. RESULTS: Forty-two percent of countries permit lay providers to perform HIV testing and 56% permit lay providers to administer pre-and post-test counseling. Comparative analysis with GARPR found that less than half (46%) of reported data from countries were consistent with their corresponding national HIV testing policy. CONCLUSIONS: Given the low uptake of lay provider use globally and their proven use in increasing HIV testing, countries should consider revising policies to support lay provider testing using rapid diagnostic tests.

Availability and Use of HIV Monitoring and Early Infant Diagnosis Technologies in WHO Member States in 2011-2013: Analysis of Annual Surveys at the Facility Level.

BACKGROUND: The Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 targets have reinforced the importance of functioning laboratory services to ensure prompt diagnosis and to assess treatment efficacy. We surveyed the availability and utilization of technologies for HIV treatment monitoring and early infant diagnosis (EID) in World Health Organization (WHO) Member States. METHODS AND FINDINGS: The survey questionnaire included 14 structured questions focusing on HIV testing, cluster of differentiation 4 (CD4) testing, HIV viral load (VL) testing, and EID and was administered annually from 2012 to 2014 through WHO country offices, with each survey covering the previous 12-mo period. Across 127 targeted countries, survey response rates were 60% in 2012, 67% in 2013, and 78% in 2014. There were encouraging trends towards increased procurement of CD4 and VL/EID instruments in reporting countries. Globally, the capacity of available CD4 instruments was sufficient to meet the demand of all people living with HIV/AIDS (PLWHA), irrespective of treatment status (4.62 theoretical tests per PLWHA in 2013 [median 7.33; interquartile range (IQR) 3.44-17.75; median absolute deviation (MAD) 4.35]). The capacity of VL instruments was inadequate to cover all PLWHA in many reporting countries (0.44 tests per PLWHA in 2013 [median 0.90; IQR 0.30-2.40; MAD 0.74]). Of concern, only 13.7% of existing CD4 capacity (median 4.3%; IQR 1.1%-12.1%; MAD 3.8%) and only 36.5% of existing VL capacity (median 9.4%; IQR 2.3%-28.9%; MAD 8.2%) was being utilized across reporting countries in 2013. By the end of 2013, 7.4% of all CD4 instruments (5.8% CD4 conventional instruments and 11.0% of CD4 point of care [POC]) and 10% of VL/EID instruments were reportedly not in use because of lack of reagents, the equipment not being installed or deployed, maintenance, and staff training requirements. Major limitations of this survey included under-reporting and/or incomplete reporting in some national programmes and noncoverage of the private sector. CONCLUSION: This is the first attempt to comprehensively gather information on HIV testing technology coverage in WHO Member States. The survey results suggest that major operational changes will need to be implemented, particularly in low- and middle-income countries, if the 90-90-90 targets are to be met.

Field accuracy of fourth-generation rapid diagnostic tests for acute HIV-1: a systematic review.

INTRODUCTION: Fourth-generation HIV-1 rapid diagnostic tests (RDTs) detect HIV-1 p24 antigen to screen for acute HIV-1. However, diagnostic accuracy during clinical use may be suboptimal. METHODS: Clinical sensitivity and specificity of fourth-generation RDTs for acute HIV-1 were collated from field evaluation studies in adults identified by a systematic literature search. RESULTS: Four studies with 17 381 participants from Australia, Swaziland, the United Kingdom and Malawi were identified. All reported 0% sensitivity of the HIV-1 p24 component for acute HIV-1 diagnosis; 26 acute infections were missed. Specificity ranged from 98.3 to 99.9%. CONCLUSION: Fourth-generation RDTs are currently unsuitable for the detection of acute HIV-1.

HIV self-testing in resource-limited settings: regulatory and policy considerations.

HIV self-testing (HIVST) is an emerging HIV testing strategy intended to address challenges of increasing access to preliminary knowledge of serostatus. It offers the potential for tests and testing to reach more people than previously possible, including those who do not seek testing in facilities. With approval of an HIV self-test kit in the USA, increasing evidence from public pilot programs in sub-Saharan Africa showing high acceptability and feasibility, and evidence of the informal sale of rapid HIV test kits in the private sector, options for individuals to access HIV self-testing, as well as consumer-demand, appear to be increasing. More recently WHO and UNAIDS have explored self-testing as an option to achieving greater HIV testing coverage to support global treatment targets. However, for resource-limited settings, technological development, diagnostic device regulation and quality assurance policies are lagging behind. This commentary will examine regulatory and policy issues with HIVST, given its increased prominence as a potential part of the global HIV/AIDS response.

Challenges and priorities in the management of HIV/HBV and HIV/HCV coinfection in resource-limited settings.

Liver disease due to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is now emerging as an increasing cause of morbidity and mortality in human immunodeficiency virus- (HIV-) infected persons in resource-limited settings (RLS). Existing management guidelines have generally focused on care in tertiary level facilities in developed countries. Less than half of low-income countries have guidance, and in those that do, there are important omissions or disparities in recommendations. There are multiple challenges to delivery of effective hepatitis care in RLS, but the most important remains the limited access to antiviral drugs and diagnostic tests. In 2010, the World Health Assembly adopted a resolution calling for a comprehensive approach for the prevention, control, and management of viral hepatitis. We describe activities at the World Health Organization (WHO) in three key areas: the establishment of a global hepatitis Program and interim strategy; steps toward the development of global guidance on management of coinfection for RLS; and the WHO prequalification program of HBV and HCV diagnostic assays. We highlight key research gaps and the importance of applying the lessons learned from the public health scale-up of ART to hepatitis care.

WHO comparative evaluation of serologic assays for Chagas disease.

BACKGROUND: Evaluation of commercially available test kits for Chagas disease for use in blood bank screening is difficult due to a lack of large and well-characterized specimen panels. This study presents a collaborative effort of Latin American blood centers and the World Health Organization (WHO) to establish such a panel. STUDY DESIGN: A total of 437 specimens, from 10 countries were collected and sent to the WHO Collaborating Center in São Paulo and used to evaluate 19 screening assays during 2001 through 2005. Specimens were assigned a positive or negative status based on concordant results in at least three of the four confirmatory assays (indirect immunofluorescence, Western blot, radioimmunoprecipitation assay, and recombinant immunoblot). RESULTS: Of the 437 specimens, 168 (39%) were characterized as positive, 262 (61%) were characterized as negative, and 7 (2%) were judged inconclusive and excluded from the analysis. Sensitivity and specificity varied considerably: 88 to 100 and 60 to 100 percent, respectively. Overall, enzyme immunoassays (EIAs) performed better than the other screening assays. Four EIAs had both parameters higher than 99 percent. Of the four confirmatory assays, only the RIPA gave a 100 percent agreement with the final serologic status of the specimens. CONCLUSION: The sensitivities and specificities of at least four of the commercially available EIAs for Chagas disease are probably high enough to justify their use for single-assay screening of blood donations. Our data suggest that the majority of commercially available indirect hemagglutination assays should not be used for blood donor screening and that the RIPA could be considered a gold standard for evaluating the performance of other assays.