HIV Diagnostics Research Articles

The Role of Voluntary Counselling and Testing Points (VCTs) in HIV Diagnostics – Analysis of VCTs Activity in Poland in the Context of Local and European Epidemiology

Abstract Screening tests are now readily accessible, quick and highly sensitive. Diagnostics of HIV infections involves serological testing followed by confirmation tests by molecular biology methods (NAAT). Fast, accurate, anonymous and free HIV testing has been provided by Voluntary Counselling and Testing Points (VCTs) for over 20 years to any adult in Poland, regardless of nationality. Additionally, the educational activities are conducted aimed at informing people from various social backgrounds about HIV prevention and diagnostic possibilities, as well as other sexually transmitted infections (STIs). The aim of the article was to present the procedures for the operation of VCTs in Poland, their location, testing scheme and a summary of the activities that promote such points in the medical community. Between 2019 and 2023, 157,833 people registered for HIV testing in VCTs in Poland, of which 10,177 (6.45%) were foreigners. In the analyzed period, the number of tests among foreigners visiting VCTs in Poland almost doubled, from 1,552 in 2019 to 2,827 in 2023. In addition, a higher percentage of positive results was recorded among foreigners – 5.08% compared to Poles – 1.24%. The frequency analysis of positive results detection reported in VCTs vs. National Institute of Public Health NIH – National Research Institute showed that, on average 26% (2,342/8,891) of positive results in Poland from 2019–2023 were detected in the framework of tests carried out in VCTs. The operation of VCT points in Poland enables the reaching of a larger group of people, especially key adult populations. It is a valuable complement to routine diagnostics outside the health care system.

HIV Diagnostics and Vaccines: It Takes Two to Tango.

Current serologic tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests are needed that are agnostic to the vaccination status of tested individuals (ie, positive only for true HIV-1 infection). Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serologic HIV tests for concurrent deployment with HIV vaccines.

Recent advances in HIV diagnostics: Point-of-care CD4 + T-cell count & viral load assays.

Recent advances in HIV diagnostics: Point-of-care CD4 + T-cell count & viral load assays.

The 35th anniversary of the North-Western District center for AIDS prevention and control at the Saint Petersburg Pasteur Institute

The organization of the North-Western District Center for AIDS Prevention and Control (AIDS Center) originates from the onset of the HIV epidemic in the Russian Federation. Over the 35 years of work, the staff of the AIDS Center has made an invaluable contribution to the development of HIV diagnostics, the introduction of new clinical and preventive technologies, patient counseling, and training of qualified personnel. The anniversary article highlights the main stages regarding establishment of the AIDS Center as a structural unit of the Saint Petersburg Pasteur Research Institute. The versatile naturally multidisciplinary functions and tasks related to the AIDS Center organization, its major Russia-wide and global achievements are considered. Special attention is paid to the long-term international cooperation, the results of diverse implemented programs and projects supported by the World Health Organization (WHO) as well as the Joint United Nations Programme on HIV/AIDS. The AIDS Center continues to cooperate with the main scientific facilities such as the Pavlov First Saint Petersburg State Medical University, Institute of Experimental Medicine, N.P. Bekhtereva Institute of the Human Brain of the Russian Academy of Sciences, etc. The ongoing joint research invariably contributes to assessing the epidemiology and clinical course of various viral infections and comorbid conditions. The knowledge acquired becomes regularly summarized and published in a series of monographs, journal articles being presented demonstrated at conferences of various levels. Currently, the AIDS Center is represented by several structural divisions continuing to conduct practical and scientific activities on investigating HIV and viral hepatitis.

Towards Novel HIV-1 Serodiagnostic Tests without Vaccine-Induced Seroreactivity.

Vaccine-induced seroreactivity/positivity (VISR/P) poses a significant and common challenge to HIV vaccine implementation, as up to 95% of vaccine recipients may be misclassified as having HIV infection by current HIV screening and confirmatory serological assays. We investigated whether internal HIV proteins could be used to overcome VISR and discovered a set of 4 antigens (gp41 endodomain, p31 integrase, p17 matrix protein, and Nef) that are recognized by antibodies produced in individuals with HIV infection but not in vaccinated individuals. When evaluated in a multiplex double-antigen bridging ELISA, this antigen combination had specificities of 98.1% prevaccination and 97.1% postvaccination, demonstrating the assay is minimally impacted by vaccine-induced antibodies. The sensitivity was 98.5%, further increasing to 99.7% when p24 antigen testing was included. Results were similar across HIV-1 clades. Although more technical advancements will be desired, this research provides the groundwork for the development of new fourth-generation HIV tests unaffected by VISR. IMPORTANCE While the detection of HIV infection is accomplished by several methods, the most common are serological tests that detect host antibodies produced in response to viral infection. However, the use of current serological tests may present a significant challenge to the adoption of an HIV vaccine in the future because the antibodies to HIV antigens detected in currently available tests also tend to be included as antigens in the HIV vaccines in development. The use of these serological tests may thus result in the misclassification of vaccinated HIV-negative individuals, which can have potential for significant harms for individuals and could prevent the widespread adoption and implementation of HIV vaccines. Our study aimed to identify and evaluate target antigens for inclusion in new serological tests that can be used to identify HIV infections without interference from vaccine-induced antibodies but also fit within existing platforms for HIV diagnostics.

The feasibility and acceptability of integrating hepatitis C and HIV diagnostic testing on centralized molecular laboratory platforms in Myanmar.

In Myanmar, 1.3 million people have been exposed to hepatitis C (HCV). However, public sector access to viral load (VL) testing for HCV diagnosis remains limited; ten near-point-of-care (POC) devices are available nationally. Myanmar's National Health Laboratory (NHL) has surplus capacity on centralized molecular testing platforms used for HIV diagnostics, presenting an opportunity for integrating HCV testing to expand overall testing capacity. This pilot assessed the operational feasibility and acceptability of HCV/HIV integrated testing implemented with a comprehensive package of supportive interventions. HCV VL samples were collected prospectively from consenting participants at five treatment clinics and tested at Myanmar's NHL (October 2019-February 2020) on the Abbott m2000. To optimize integration, laboratory human resources were bolstered, staff trainings were offered, and existing laboratory equipment was serviced/repaired as needed. Diagnostics data during the intervention period were compared against HIV diagnostics data in the seven months prior. We conducted three time and motion analyses at the laboratory and semi-structured interviews with laboratory staff to assess time needs and program acceptability. 715 HCV samples were processed during the intervention period with an average test processing time of 18 days (IQR: 8-28). Despite adding HCV testing, average monthly test volumes were 2,331 for HIV VL and 232 for early infant diagnosis (EID), comparable to the pre-intervention period. Processing times were 7 days for HIV VL and 17 days for EID, also comparable to the pre-intervention period. HCV test error rate was 4.3%. Platforms utilization increased from 18.4% to 24.6%. All staff interviewed were supportive of HCV and HIV diagnostics integration; suggestions were made for broader implementation and expansion. With a package of supportive interventions, integration of HCV and HIV diagnostics on a centralized platform was operationally feasible, did not adversely impact HIV testing, and was acceptable to laboratory staff. In Myanmar, integrated HCV VL diagnostic testing on centralized platforms may be an important addition to existing near-POC testing in expanding national testing capacity for HCV elimination.

Diagnosis of HIV infection using mass community rapid testing in Santiago, Chile

BackgroundChile has had the highest increase in new HIV infections in Latin America in the last ten years. Therefore, Chile should follow the WHO recommends on the use of rapid testing in the community to reduce the enormous barriers to diagnosis that exist until today. The objective of this study was to evaluate the performance of rapid tests prior diagnosis of HIV infection in the general population using mass testing in the community. Study designSix HIV rapid tests were evaluated using positive and negative plasma panels. Moreover, the Ag/Ab assays were revaluated using whole blood obtained from HIV-positive and seronegative individuals. After evaluation, we selected an Ag/Ab test to determine the prevalence of HIV infection in the study participants. A total of 3,102 people were included. ResultsIn the evaluation with plasma and whole blood the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) was 100% for the tests. In the 3102 study participants, we found a total of 41 reactive individuals. After adjustments, a total of 32 people who participated in the study were diagnosed with HIV infection. These results indicate that the Ag/ab assay had a high sensitivity, specificity, NPV, and PPV. ConclusionsWe validated available rapid tests and demonstrated the feasibility of mass testing in the community. Confidentiality was guaranteed with a link to healthcare. After adjustments, we found an HIV infection prevalence of 1.03%. This is twice the estimate of official sources. Therefore, rapid tests have adequate sensitivity and specificity for use in HIV diagnostics.

Adolescents and Young Adults: The Pediatrician's Role in HIV Testing and Pre- and Postexposure HIV Prophylaxis.

Most sexually active youth in the United States do not believe that they are at risk for contracting HIV and have never been tested. Creating safe environments that promote confidentiality and respect, obtaining an accurate sexual and reproductive health assessment, and providing nonstigmatizing risk counseling are key components of any youth encounters. Pediatricians can play a key role in preventing and controlling HIV infection by promoting risk-reduction counseling and offering routine HIV testing and prophylaxis to adolescent and young adult (youth) patients. In light of persistently high numbers of people living with HIV in the United States and documented missed opportunities for HIV testing, the Centers for Disease Control and Prevention and the US Preventive Services Task Force recommend universal and routine HIV screening among US populations, including youth. Recent advances in HIV diagnostics, treatment, and prevention help support this recommendation. This clinical report reviews epidemiological data and recommends that routine HIV screening be offered to all youth 15 years or older, at least once, in health care settings. After initial screening, youth at increased risk, including those who are sexually active, should be rescreened at least annually, and potentially as frequently as every 3 to 6 months if at high risk (male youth reporting male sexual contact, active injection drug users, transgender youth; youth having sexual partners who are HIV-infected, of both genders, or injection drug users; youth exchanging sex for drugs or money; or youth who have had a diagnosis of or have requested testing for other sexually transmitted infections). Youth at substantial risk for HIV acquisition should be routinely offered HIV preexposure prophylaxis, and HIV postexposure prophylaxis is also indicated after high-risk exposures. This clinical report also addresses consent, confidentiality, and coverage issues that pediatricians face in promoting routine HIV testing and HIV prophylaxis for their patients.

Stratifying Sepsis in Uganda Using Rapid Pathogen Diagnostics and Clinical Data: A Prospective Cohort Study.

The global burden of sepsis is concentrated in sub-Saharan Africa, where extensive pathogen diversity and limited laboratory capacity challenge targeted antimicrobial management of life-threatening infections. In this context, established and emerging rapid pathogen diagnostics may stratify sepsis patients into subgroups with prognostic and therapeutic relevance. In a prospective cohort of adults (age ≥18 years) hospitalized with suspected sepsis in Uganda, we stratified patients using rapid diagnostics for HIV, tuberculosis (TB), malaria, and influenza, and compared clinical characteristics and 30-day outcomes across these pathogen-driven subgroups. From April 2017 to August 2019, 301 adults were enrolled (median age, 32 years [interquartile range, 26-42 years]; female, n = 178 [59%]). A total of 157 patients (53%) were HIV infected. Sixty-one patients (20%) tested positive for malaria, 52 (17%), for TB (including 49 of 157 [31%] HIV-infected patients), and 17 (6%), for influenza. Co-infection was identified in 33 (11%) patients. The frequency of multi-organ failure, including shock and acute respiratory failure, was greatest among patients with HIV-associated TB. Mortality at 30 days was 19% among patients with malaria, 40% among patients with HIV-associated TB, 32% among HIV-infected patients without microbiological evidence of TB, 6% among patients with influenza, and 11% among patients without a pathogen identified. Despite improvements in anti-retroviral delivery, the burden of sepsis in Uganda remains concentrated among young, HIV-infected adults, with a high incidence of severe HIV-associated TB. In parallel with improvements in acute-care capacity, use of rapid pathogen diagnostics may enhance triage and antimicrobial management during emergency care for sepsis in sub-Saharan Africa, and could be used to enrich study populations when trialing pathogen-specific treatment strategies in the region.

Identification, Genetic Characterization and Validation of Highly Diverse HIV-1 Viruses for Reference Panel Development.

The continued diversification of HIV poses potentially significant challenges to HIV diagnostics and therapeutics. The dynamic evolution of emerging variants is highlighted in countries such as Cameroon in West Central Africa, where all known subtypes and circulating recombinant forms (CRFs) have been shown to be prevalent. We obtained several hundred HIV-positive plasma and viruses from this region for characterization and identification of highly divergent HIV strains. A total of 163 viral strains were cultured to high titers and high volumes using donor peripheral blood mononuclear cells (PBMCs). Initially, 101 viruses representing 59 strains were well characterized and categorized. Results showed that the viral load (VL) range was 0.36–398.9 × 107 copies/mL, p24 values was 0.2–1134 ng/mL. Phylogenetic analysis of thirty-six near full-length HIV-1 genomic sequences demonstrated that most recombinants were highly diverse CRF02 containing unique recombinant forms (URFs). There were seven viral isolates identified as pure subtype/sub-subtypes (F2, A1, G, and D), six as CRFs (CRF06, CRF18, and CRF22), and ten as URFs. These extensively characterized reagents reflect the current dynamic and complex HIV epidemic in Cameroon and provide valuable insights into the potential phylogenetic evolutionary trend of global HIV molecular epidemiology in the future. These materials may be useful for development of HIV validation and reference panels to evaluate the performance of serologic antigen and nucleic acid assays for their ability to detect and quantitate highly divergent HIV strains.

Robin Shattock: novel vaccine developer

Robin Shattock: novel vaccine developer

Current status of HIV self-testing application

HIV self-testing is a key measure and strategy to expand the coverage of HIV testing in key populations, which has great value in application and high acceptance in key populations. The World Health Organization (WHO) issued the Guidelines on HIV self-testing and partner notification in 2016 to support the application of HIV self-testing and provide specific guidance for countries and organizations to develop corresponding public health policies for the purpose of improving the accessibility and utilization of HIV diagnostics. HIV self-testing has been promoted in many countries and has achieved great results. This article provides an overview of the current domestic and international HIV self-testing policies, intervention models, the use of self-testing kits, the accuracy of self-testing kits, and the application of pre- and post-testing counseling services to provide reference for the further improvement of HIV self-testing in China.

Aligning diagnostics to the point-of-care: lessons for innovators, evaluators and decision-makers from tuberculosis and HIV

Diagnostics, including those that work at point-of-care, are an essential part of successful public health responses to infectious diseases and pandemics. Yet, they are not always used or fit intended...

Automated HIV screening in the emergency department –earlier diagnosis, improved clinical outcomes

Abstract Background HIV/AIDS is a public health problem worldwide because undiagnosed patients maintain onward transmission. To stop viral transmission an upscale in diagnostics is needed so that more patients start treatment; patients on treatment and with undetectable viral load do not transmit the virus to other persons (“Treatment as Prevention”). Objectives We aimed at identifying more HIV infections in the emergency Department (ED) and at doing so earlier in the course of disease. Methods we designed an automated and clinician independent HIV screening project in the ED. Electronic Medical Record (EMR) automatically generates a request for HIV antibody (HIV Ab) test when a patient: a) is 18-65 years of age and has a request for any blood test; b) is not identified in the EMR as being HIV infected; c) does not have an HIV Ab in the EMR in the previous year. Nursing staff receive a visual warning of patients' eligibility for screening and an extra tube label is printed out for HIV testing. The patient is informed of screening at the moment of blood drawing and an <<opt-out >> strategy is applied (optional verbal informed consent or <<opt-out >> of screening). Results In 16 months, a total of 21.487 people were eligible for screening. 18.072 HIV Ab screening tests were done. The opt-out rate was 6.3% and there were 44 new HIV diagnostics (prevalence rate 0.24%). Late presenting patients (baseline CD4 counts <350) dropped from an average of 56% in the previous 6 years at our institution to 36.3%. Median CD4 count at diagnostics went up from 192 to 388 cells/mm³. Conclusions An automated and clinician independent HIV screening program in the ED proved to be successful at identifying more HIV patients and at tackling the problem of late presentation. Diagnosing early in the course of infection is beneficial for the individual patient, but also represents a gain in general public health because onward transmission is stopped by starting antiretroviral treatment. Key messages Early diagnosis through universal screening. Treatment as prevention.

COVID-19 complications in South Africa

Coronavirus South Africa has been developing control measures to tackle prevalent infectious diseases, particularly tuberculosis and HIV. However, with the onset of coronavirus disease 2019 (COVID-19), those resources, particularly those for diagnostics and community health care provision, were rerouted. In a Perspective, Abdool Karim and Abdool Karim discuss the possible implications of underresourcing tuberculosis and HIV diagnostics, health care, and research while the focus is on COVID-19. In particular, there are questions about whether progress in controlling tuberculosis and HIV will be reversed and if these and other prevalent infectious diseases alter the behavior of COVID-19, and vice versa. Science , this issue p. [366][1] [1]: /lookup/doi/10.1126/science.abd1072

Valuing Simplicity: Developing a Good Point of Care Diagnostic.

Point-of-care testing promises laboratory-based precision in settings that do not have easy access to laboratories or where processing tests takes too long or is too costly. Developers and global health actors stress values and norms such as simplicity, rapidity and accuracy for realizing diagnostic innovations that work at point of care and are aligned to the specific requirements of point-of-care settings. This paper uses fieldwork among diagnostic manufacturers, scientists, donors, members of civil society, industry consultants, international organizations, regulators, policymakers, programme officers, lab technicians, and clinicians involved in development and implementation of tuberculosis and HIV diagnostics, to examine how norms and values of what constitutes a good point-of-care diagnostic are operating in practice through both top-down and bottom-up dynamics. It draws the link between design, evidence and adoption of diagnostics and how the different actors interpret the values underpinning the new practice. The analysis draws on literature on valuation practices, evidence-making and technology design in science and technology studies and medical sociology. The findings reveal how these values constitute innovation, implementation, and evaluation practices across global and local (India) sites, with important consequences for funding of health infrastructure, capacity, and training resources for addressing some of the existing structural inequalities. Dominant values currently defining point of care diagnostics risk exacerbating health inequalities between those who do and do not have the necessary social and financial resources to access better equipped and functioning healthcare facilities, especially in resource constrained settings.

An immunoassay cassette with a handheld reader for HIV urine testing in point-of-care diagnostics.

Currently, most HIV tests are performed with blood samples, or alternatively saliva samples are used for HIV testing. Simple HIV tests need to be performed in hospitals or other medical agencies instead of more invasive HIV blood tests. To enable point-of-care (POC) HIV diagnostics, based on a recently developed lateral flow strip for HIV urine testing, a microfluidic immunoassay cassette with a handheld optical reader is developed. Based on lateral flow strip with gold colloid reporter, the integrated immunoassay cassette can perform sample introduction, metering, discharging, applying and detection which simplifies HIV testing. An indicator is incorporated into the cassette to guide sample introduction based on color change, and further, the excess test sample is stored inside the sealed cassette to avoid any contamination. The low-cost handheld optical reader can provide a test result within a few seconds, which is useful for simple, sensitive and affordable HIV onsite detection. Instead of using normal white LEDs, a customized back light module embedded with green LEDs is adopted to illuminate the lateral flow strip with an appropriate working current to achieve optimal performance. Compared to the standard lateral flow strips using a benchtop reader, with the disposable immunoassay cassette assisted by the handheld optical reader, more convenient, easier-to-operate, and more affordable HIV urine testing can be achieved in POC diagnostics.

Highlights From the 2019 HIV Diagnostics Conference: Optimizing Testing for HIV, STIs, and HCV.

Highlights From the 2019 HIV Diagnostics Conference: Optimizing Testing for HIV, STIs, and HCV.

Aligning in the dark: Variable and shifting (user-) settings in developing point-of-care diagnostics for tuberculosis and HIV.

To be effective, healthcare technologies should be attuned to particular contexts of use. This article examines how such attuning is articulated in global innovation practices for tuberculosis and HIV diagnostics, and to what effect. It examines the development of point-of-care (POC) diagnostics - promised to be designed for users outside laboratories or in resource constrained settings - to study what developers and implementers do to align diagnostic technologies to the POC. Fieldwork among global health actors involved in diagnostic development, including manufacturers, donors, industry consultants, international organizations, policymakers, regulators and researchers, is combined with fieldwork among users of diagnostics in India, including decision-makers, NGOs, program officers, laboratory technicians and nurses. The article adds to STS's theory of alignment and user interaction, where the setting and user to which developers and implementers of global health diagnostics align are multiple, varied, emerging and keep shifting. The characteristics of a local user setting include multiple engaged and imagined user settings, but also the settings of developers, of global intermediaries, competitors and diseases. As such, alignment is happening across multiple dimensions and scales and has an important temporal dimension. The results reveal how alignment happens to some extent in the dark, characterized by uncertainty about the elements that should align. Standardizing elements, politics and scarce resources cause frictions in the temporalities of aligning and over what constitutes a well-aligned diagnostic.

Estimated dates of detectable infection (EDDIs) as an improvement upon Fiebig staging for HIV infection dating.

Accurate methods for determining the duration of HIV infection at the individual level are valuable in many settings, including many critical research studies and in clinical practice (especially for acute infection). Since first published in 2003, the 'Fiebig staging system' has been used as the primary way of classifying early HIV infection into five sequential stages based on HIV test result patterns in newly diagnosed individuals. However, Fiebig stages can only be assigned to individuals who produce both a negative and a positive test result on the same day, on specific pairs of tests of varying 'sensitivity'. Further, in the past 16 years HIV-testing technology has evolved substantially, and three of the five key assays used to define Fiebig stages are no longer widely used. To address these limitations, we developed an improved and more general framework for estimating the duration of HIV infection by interpreting any combination of diagnostic test results, whether obtained on single or multiple days, into an estimated date of detectable infection, or EDDI. A key advantage of the EDDI method over Fiebig staging is that it allows for the generation of a point estimate, as well as an associated credibility interval for the date of first detectable infection, for any person who has at least one positive and one negative HIV test of any kind. The tests do not have to be run on the same day; they do not have to be run during the acute phase of infection and the method does not rely on any special pairing of tests to define 'stages' of infection. The size of the interval surrounding the EDDI (and therefore the precision of the estimate itself) depends largely on the length of time between negative and positive tests. The EDDI approach is also flexible, seamlessly incorporating any assay for which there is a reasonable diagnostic delay estimate. An open-source, free online tool includes a user-updatable curated database of published diagnostic delays. HIV diagnostics have evolved tremendously since that original publication more than 15 years ago, and it is time to similarly evolve the methods used to estimate timing of infection. The EDDI method is a flexible and rigorous way to estimate the timing of HIV infection in a continuously evolving diagnostic landscape.