Fig 1 - uploaded by Darrel Cook
Content may be subject to copyright.
HIV testing algorithm. Abbreviations: gen: generation; EIA: enzyme immunoassay; NAT: nucleic acid test; neg: negative; indet: indeterminate; pos: positive.
Source publication
Objectives
We compared a 3rd generation (gen) and two 4th gen HIV enzyme immunoassays (EIAs) to pooled nucleic acid testing (PNAT) for the identification of pre- and early seroconversion acute HIV infection (AHI).
Study design
9550 specimens from males >18 years from clinics attended by men who have sex with men were tested by Siemens ADVIA Centau...
Contexts in source publication
Context 1
... serum specimens were screened by a 3rd gen (Siemens ADVIA Centaur 1 HIV-1/O/2; Siemens, Mississauga, Ontario, Canada) and two 4th gen HIV EIAs (Siemens ADVIA Centaur 1 HIV Combo and Abbott ARCHITECT 1 HIV Ag/Ab Combo; Abbott Diagnostics, Mississuaga, Ontario, Canada) (Fig. 1). The Centaur 1 instrument uses a single disposable pipette tip for each sample tested, whereas the ARCHITECT 1 uses a single probe with washing between specimens. To reduce the possibility of RNA cross- contamination following serological screening of samples on the Centaur 1 , aliquots were removed for subsequent testing by ARCHITECT ...
Context 2
... used to trigger additional testing for AHI. However, among the NAT negative, HIV EIA non-reactive subjects, 457 specimens had Siemens 4th gen s/c values in the equivocal range (Supplementary Fig. S1). Thus, a considerable number of individual NATs would need to be performed for equivocal EIA results for this assay to provide one additional AHI diagnosis. ...
Similar publications
Citations
... the assumption that the number of nonzero (defective in the context of group testing) components in the variables to be estimated is sufficiently small. The reduction in the number of tests reduces the testing costs; hence, the application of group testing to various diseases such as HIV [4] and hepatitis virus [5], [6] has been discussed. In addition, the need to detect elements in heterogeneous states from a large population is common not only in medical tests but also in various other fields. ...
We study the inference problem in the noisy group testing to identify defective items from the perspective of the decision theory. We introduce Bayesian inference and consider the Bayesian optimal setting in which the true generative process of the test results is known. We demonstrate the adequacy of the posterior marginal probability in the Bayesian optimal setting as a diagnostic variable based on the area under the curve (AUC). Using the posterior marginal probability, we derive the general expression of the optimal cutoff value that yields the minimum expected risk function. Furthermore, we evaluate the performance of the Bayesian group testing without knowing the true states of the items: defective or non-defective. By introducing an analytical method from statistical physics, we derive the receiver operating characteristics curve, and quantify the corresponding AUC under the Bayesian optimal setting. The obtained analytical results precisely describes the actual performance of the belief propagation algorithm defined for single samples when the number of items is sufficiently large.
... It is expected that when the prevalence (fraction of the defective items) is sufficiently small, the defective items can be accurately identified using an appropriate inference method, as with sparse estimation [2], [3], wherein an underdetermined problem is solved under the assumption that the number of nonzero (defective in the context of group testing) components in the variables to be estimated is sufficiently small. The reduction in the number of tests reduces the testing costs; hence, the application of group testing to various diseases such as HIV [4] and hepatitis virus [5], [6] has been discussed. In addition, the need to detect elements in heterogeneous states from a large population is common not only in medical tests but also in various other fields. ...
We study the inference problem in the group testing to identify defective items from the perspective of the decision theory. We introduce Bayesian inference and consider the Bayesian optimal setting in which the true generative process of the test results is known. We demonstrate the adequacy of the posterior marginal probability in the Bayesian optimal setting as a diagnostic variable based on the area under the curve (AUC). Using the posterior marginal probability, we derive the general expression of the optimal cutoff value that yields the minimum expected risk function. Furthermore, we evaluate the performance of the Bayesian group testing without knowing the true states of the items: defective or non-defective. By introducing an analytical method from statistical physics, we derive the receiver operating characteristics curve, and quantify the corresponding AUC under the Bayesian optimal setting. The obtained analytical results precisely describes the actual performance of the belief propagation algorithm defined for single samples when the number of items is sufficiently large.
... In addition, innovative testing approaches, akin to those currently available for HIV, have also emerged including rapid tests, saliva-based tests, selftesting, and home-based testing approaches 33,34 . New methods of specimen collection that is less invasive are currently under development as well as novel approaches such as micropooling, which is done for acute HIV screening in select areas 35 . ...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, was first detected in China in December 2019 and has rapidly spread throughout the world. Globally, the impact of COVID-19 has been severe with more than half a million deaths over 6 months; in contrast, the HIV pandemic has resulted in over 32 million deaths worldwide over 40 years. This paper reviews the current epidemiology of COVID-19, summarizes its relationship to HIV, identifies synergies in our response, and suggests actions that can be taken to curtail the spread of COVID-19 among persons living with HIV (PLWH). Our understanding of the epidemiology, clinical presentation, prevention, and treatment of COVID-19 has evolved rapidly as they did with HIV. Epidemiologically, there are similarities between the two viruses including asymptomatic spread, disproportionate impact on persons of color, need for rapid diagnostic testing, and lack of a cure or vaccine. PLWH do not appear generally to have an increased incidence of COVID-19 infection or a more severe course of disease. Clinical trials to identify potential treatment and prevention options for COVID-19 have included antiretrovirals used to treat HIV that have not been efficacious. Public health responses overlap between the two pandemics including the need for behavior change and containment strategies such as contact tracing. As the SARS-CoV-2 pandemic evolves, the path forward to controlling, preventing, and treating COVID-19 can be informed by lessons learned from HIV as we seek to control the spread of both viral pandemics.
... Band-based HIV antibody confirmatory assays such as WB and RIBA remained to be the mostly used strategy worldwide [20]. They are able to detect HIV specific antibodies in most subjects, but acute HIV infection and late-stage HIV infection maybe negative or indeterminate for HIV antibody tests [3, [21][22][23]. Previous studies have proven that the sequential emergence of HIV-1 antibodies associates with the progress of HIV-1 infection [11,12,[24][25][26], therefore the laboratory diagnosis of HIV infection is helpful for understanding the local epidemic and may partly reflect the effectiveness of HIV/AIDS intervention. ...
The number, intensity and order of emergence of HIV-1 specific antibodies in serum or plasma were associated with the stage of HIV-1 infection. In this study, we retrospectively analyzed the HIV-1 confirmatory results tested by western blot (WB) or recombination immunoblot assay (RIBA) in Wuhan, 2012-2018, to access the profiles of HIV-1 specific antibodies. A total of 14432 HIV-suspected serum or plasma samples collected from local hospitals and other HIV screening laboratories were further screened by two 4th generation enzyme-linked immunosorbent assay (ELISA) kits in our laboratory, of which 11068 specimens (76.69%) had at least one positive ELISA result and thereby were finally confirmed with WB or RIBA. RIBA had identified 652 (81.09%) positive and 13 (1.62%) indeterminate cases from July 1, 2014 to January 7, 2015, while WB had identified 8358 (81.43%) positive and 643 (6.26%) indeterminate cases in the other times during 2012-2018. The indeterminate rate of WB was significant higher than that of RIBA (p<0.001). Although the number of HIV-1 infected subjects increased significantly from 2012 (n = 911) to 2018 (n = 1578), the positive rate of HIV-1 antibodies decreased markedly from 70.08% in 2012 to 58.79% in 2018 (p<0.001). The most commonly observed antibody profile was gp160+gp120+p66+(p55+)p51+gp41+p31+p24+p17+ (4131, 49.43%) for WB-MP and gp160+gp120+gp41+p31+p24+p17+ (382, 58.59%) for RIBA-WANTAI, and the absence of reactivity to three possible serologic markers for recent HIV-1 infection, p31, p66, and p51, increased significantly from 2012 to 2018, with the overall rate of 17.03%, 9.40%, and 15.15%, respectively. The suspected acute HIV-1 infection was also observed to be increased in recent years, with an overall rate of 1.00%. Our results indicated the detection rate had decreased for HIV-1 infection, but increased for suspected recent and acute HIV-1 infection during 2012-2018, reflecting the efforts of intervention among high risk population.
... Therefore, until more appropriate point-of-care diagnostics for acute HIV infection detection are introduced, laboratory HIV Ag/Ab immunoassay or pooled nucleic acid test may be the dependable approach to detect acute HIV infection among Africans living in settings with high HIV incidence. 22 ...
Detection of acute HIV infection is a unique problem that fourth-generation HIV assays were expected to alleviate. In this commentary, we draw attention to the limitations and challenges with use of currently available rapid antigen-antibody (Ag/Ab) combination tests for detection of acute HIV infection in sub-Saharan Africa. Laboratory-based HIV-1 Ag/Ab immunoassays are complex, requiring specialized equipment and handling that are currently not affordable in many settings in Africa. The point-of-care Ag/Ab platform on the other hand is easier to deploy and potentially more accessible in resource-limited settings. However, available fourth-generation HIV-1 rapid diagnostic tests have demonstrated poor performance characteristics in field studies where non-B subtypes of HIV-1 dominate. The potential for point-of-care HIV-1 Ag/Ab diagnostics to significantly improve detection of acute HIV infection remains yet to be realized in sub-Saharan Africa. Assay platforms need to be optimized to identify local circulating subtypes, and optimal algorithms need to be determined.
... Mit der Vergleichbarkeit von venösem Blut und Blut aus der Fingerbeere ist zudem eine Vereinfachung der Probengewinnung möglich, die nun mit einfachsten Methoden erfolgen kann. Pooling-Methoden wurden ebenfalls 2014 bei einer Studie aus Kanada angewandt, bei der Pooling die Detektion frischer HIV-Infektionen in einer risikoreichen Bevölkerungsgruppe im Vergleich zu 3. und 4. Generations-Enzymtestungen verbessern konnten[75]. Bei einer Studie in Süd-Korea von 2013 konnte die Minipool-Methode erfolgreich beim Therapiemonitoring eingesetzt werden[76].Ebenfalls 2013 wurde in Kenia nachgewiesen, dass Pooling auch beim Therapiemonitoring von Kindern erfolgreich angewendet werden kann[77]. ...
Hintergrund: Um eine optimale Einstellung einer HIV-Therapie gewährleisten zu können, sind die regelmäßige Kontrolle der Viruslast und der CD4-Zellzahl notwendig. Die hohen Kosten, die das Monitoring der Viruslast bei einer steigenden Anzahl von Patienten, die eine HIV-Therapie erhalten, hervorruft, sind jedoch für viele Länder nicht zu bewältigen. Pooling-Strategien konnten bei einem festgesetzten und klinisch sinnvollen Viruslast-Grenzwert die Kosten des Monitorings effizient reduzieren. Dies galt jedoch bei einer niedrigen Rate an Patienten, die über dem Viruslast-Grenzwert lagen. In ärmeren Ländern ist die HIV-Infektionsrate oft besonders hoch und die Rate an Patienten mit hohen Viruslasten erscheint höher. Methoden: Es wurden Informationen von Testanforderungsbögen ausgewertet, um Selektionskriterien zu finden, die die Wahrscheinlichkeit erhöhten, eventuelle Therapieversager zu erkennen. Anschließend wurde Blutplasma von 300 Patientenproben, die die gefundenen Selektionskriterien erfüllten, in drei 10x10 Matrices gepoolt. Zur Auswertung der Pools wurde ein bereits vorher entwickelter Algorithmus verwendet. Ergebnisse: Als Selektionskriterien wurden gefunden, dass nur Patienten, die mindestens 16 Jahre alt waren und eine auf einem nicht-nukleosidischen Reverse-Transkriptase-Inhibitor beruhende Therapie erhielten (first-line Therapie), für das Pooling geeignet waren. Die Rate an Patienten mit einer Viruslast von mindestens 1.000 HIV-1 RNA Kopien pro Milliliter unter den 300 Patientenproben betrug 11,0%. Durch die Anwendung der Matrix-Pooling-Methode konnten insgesamt 41% der Tests eingespart werden, was in einer durchschnittlichen Kostenreduktion von 1.640 US$ pro 100 Patientenproben resultierte. Dabei lag der negative prädiktive Wert bei 98% und der positive prädiktive Wert bei 100% bei einer Sensitivität von 81% und einer Spezifität von 100%. Diskussion: Pooling-Methoden sind eine Möglichkeit, bei den bisher zur Verfügung stehenden kommerziell angebotenen Viruslasttestungen Kosten einzusparen und somit die Viruslasttestung in Ländern zu ermöglichen, die bisher die Kosten dafür nicht tragen konnten.
... Persons with two positive results were considered HIVseropositive. Fingerstick specimens were tested for HIV RNA using a previously validated 9:1 pooling algorithm (14)(15)(16). ...
Background
Persons with acute HIV infection (AHI) have heightened transmission risk. We evaluated potential transmission reduction using behavioral and biomedical interventions in a randomized controlled pilot study in Malawi.
Methods
Persons were randomized 1:2:2 to standard counseling (SC), five-session behavioral intervention (BI), or behavioral intervention plus 12-weeks of antiretrovirals (ARVs; BIA). All were followed for 26–52 weeks; and, regardless of arm, referred for treatment according to Malawi-ARV guidelines. Participants were asked to refer partners for testing.
Results
Among 46 persons (9 SC, 18 BI, 19 BIA), average age was 28; 61% were male. Median viral load (VL) was 5.9 log copies/ml at enrollment: 67% (10/15) of BIA participants were suppressed (<1000 copies/ml) at week 12 vs 25% BI and 50% SC (p=0.07). Although mean number of reported condomless sexual acts in past week decreased from baseline across all arms (1.5 vs 0.3 acts), 36% experienced incident STI by 52-weeks (12% SC; 28% BI; 18% BIA). 41% (19/46) of participants referred partners (44% SC; 44% BI; 37% BIA); 15 of the partners were HIV-infected.
Conclusions
Diagnosis of AHI facilitates behavioral and biomedical risk-reduction strategies during a high-transmission period that begins years before people are typically identified and started on ARVs. Sexually transmitted infection incidence in this cohort suggests ongoing risk behaviors, reinforcing the importance of early intervention with ARVs to reduce transmission. Early diagnosis coupled with standard AHI counseling and early ARV referral quickly suppresses viremia, may effectively change behavior, and could have tremendous public health benefit in reducing onward transmission.
... Group testing is becoming a popular cost-saving alternative to individual-level testing in applications from infectious disease testing (Lewis et al., 2012;Krajden et al., 2014) to environmental monitoring (Heffernan et al., 2014). For example, the State Hygienic Laboratory (SHL) in Iowa City saved approximately $3.1 million during 2009-2014 after adopting group testing to screen female subjects for chlamydia (Jeffrey Benfer, SHL, personal communication). ...
... Extending earlier works, several authors have proposed parametric (Farrington, 1992;Vansteelandt et al., 2000;Huang, 2009;Chen et al., 2009;McMahan et al., 2012) and nonparametric (Delaigle and Meister, 2011;Delaigle et al., 2014;Wang et al., 2014;Delaigle and Hall, 2015) regression methodologies for group testing data. A drawback to the aforementioned methodologies is that they were designed only for analyzing test results obtained from assaying non-overlapping master pools; i.e., they cannot incorporate data from resolving positive master pools, testing procedures with overlapping pools, or data from quality control testing (Gastwirth and Johnson, 1994;Kim et al., 2007;Krajden et al., 2014). ...
For disease screening, group (pooled) testing can be a cost‐saving alternative to one‐at‐a‐time testing, with savings realized through assaying pooled biospecimen (e.g. urine, blood, saliva). In many group testing settings, practitioners are faced with the task of conducting disease surveillance. That is, it is often of interest to relate individuals' true disease statuses to covariate information via binary regression. Several authors have developed regression methods for group testing data, which is challenging due to the effects of imperfect testing. That is, all testing outcomes (on pools and individuals) are subject to misclassification, and individuals' true statuses are never observed. To further complicate matters, individuals may be involved in several testing outcomes. For analyzing such data, we provide a novel regression methodology which generalizes and extends the aforementioned regression techniques and which incorporates regularization. Specifically, for model fitting and variable selection, we propose an adaptive elastic net estimator under the logistic regression model which can be used to analyze data from any group testing strategy. We provide an efficient algorithm for computing the estimator along with guidance on tuning parameter selection. Moreover, we establish the asymptotic properties of the proposed estimator and show that it possesses “oracle” properties. We evaluate the performance of the estimator through Monte Carlo studies and illustrate the methodology on a chlamydia data set from the State Hygienic Laboratory in Iowa City. This article is protected by copyright. All rights reserved
... Both pooled NAT and fourth-generation HIV EIAs provide an increase yield for AHI diagnosis [54,55]. However, these assays are laboratory-based and not feasible at large scale in SSA [39]. ...
... Nucleic acid amplification test (NAT) has been used to check the primary infection. This method was a very sensitive method for detection of HIV antibodies in high risk population [10]. Among the test assays, EIA or ELISA is the best sensitive and specific assay used by several laboratories and clinics in the world to detect HIV infection. ...
In Acquired Immunodeficiency Syndrome (AIDS) routine surveillance system, it is required to identify the persons infected with Human Immunodeficiency Virus (HIV) recently or showing the clinical stages of AIDS. The sensitive and specific of the assay is essential to detect the HIV infections in early period. Human Immunodeficiency Virus (HIV) screening assay is a type of enzyme immunoassay (EIA) has gone through improvement in several generations effectively narrow the window period. The HIV specific antibodies, viral antigens are produced up to detectable level. The time is variable in different individuals to produce the HIV antibodies in the presence of the host’s immune pressure. This assay was developed from first generation to fifth generation based on its sensitivity and specificity. Due to the false positive reactivity, the accurate sensitive assay is required in field validations and routine testing of HIV infected samples. This EIA is generally used as a screening assay for blood donors and individuals those are at a risk in Acquired Immunodeficiency Syndromes (AIDS). At present, the several types of EIA are the most widely used in serological test for HIV antibodies detection.
