Low Specificity of Determine HIV1/2 RDT Using Whole Blood in South West Tanzania

Kroidl, Inge; Clowes, Petra; Mwalongo, Wolfram; Maganga, Lucas; Maboko, Leonard; Kroidl, Arne; Geldmacher, Christof; Machibya, Harun; Höelscher, Michael; Saathoff, Elmar

doi:10.1371/journal.pone.0039529

Cited by 28 publications

(30 citation statements)

References 20 publications

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“…There is evidence of Determine, STAT-PAK®, and Unigold™ showing this phenomenon in multiple countries which suggests this is a class effect rather than one specific to a particular RDT or geographic location [ 4 , 5 , 8 , 10 - 13 ]. One report suggests that weak positive results are more frequent with plasma versus whole blood [ 11 ]. Our results do not support this finding.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of HIV testing algorithms in Ethiopia: the role of the tie-breaker algorithm and weakly reacting test lines in contributing to a high rate of false positive HIV diagnoses

et al. 2015

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BackgroundIn Ethiopia a tiebreaker algorithm using 3 rapid diagnostic tests (RDTs) in series is used to diagnose HIV. Discordant results between the first 2 RDTs are resolved by a third ‘tiebreaker’ RDT. Médecins Sans Frontières uses an alternate serial algorithm of 2 RDTs followed by a confirmation test for all double positive RDT results. The primary objective was to compare the performance of the tiebreaker algorithm with a serial algorithm, and to evaluate the addition of a confirmation test to both algorithms. A secondary objective looked at the positive predictive value (PPV) of weakly reactive test lines.MethodsThe study was conducted in two HIV testing sites in Ethiopia. Study participants were recruited sequentially until 200 positive samples were reached. Each sample was re-tested in the laboratory on the 3 RDTs and on a simple to use confirmation test, the Orgenics Immunocomb Combfirm® (OIC). The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing.Results2620 subjects were included with a HIV prevalence of 7.7%. Each of the 3 RDTs had an individual specificity of at least 99%. The serial algorithm with 2 RDTs had a single false positive result (1 out of 204) to give a PPV of 99.5% (95% CI 97.3%-100%). The tiebreaker algorithm resulted in 16 false positive results (PPV 92.7%, 95% CI: 88.4%-95.8%). Adding the OIC confirmation test to either algorithm eliminated the false positives. All the false positives had at least one weakly reactive test line in the algorithm. The PPV of weakly reacting RDTs was significantly lower than those with strongly positive test lines.ConclusionThe risk of false positive HIV diagnosis in a tiebreaker algorithm is significant. We recommend abandoning the tie-breaker algorithm in favour of WHO recommended serial or parallel algorithms, interpreting weakly reactive test lines as indeterminate results requiring further testing except in the setting of blood transfusion, and most importantly, adding a confirmation test to the RDT algorithm. It is now time to focus research efforts on how best to translate this knowledge into practice at the field level.Trial registrationClinical Trial registration #: NCT01716299

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Section: Discussionmentioning

confidence: 99%

Evaluation of HIV testing algorithms in Ethiopia: the role of the tie-breaker algorithm and weakly reacting test lines in contributing to a high rate of false positive HIV diagnoses

et al. 2015

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“…Negative RDTs from the fi rst annual surveys that were confi rmed by another negative RDT in the following survey were regarded as confi rmed and not further tested. For all HIV incident cases in survey 2, negative results of the previous round were confi rmed by the testing algorithm described above [8].…”

Section: Methodsmentioning

confidence: 99%

Reasons for false-positive lipoarabinomannan ELISA results in a Tanzanian population

Kroidl¹,

Clowes²,

Mwakyelu³

et al. 2013

Scandinavian Journal of Infectious Diseases

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Lipoarabinomannan (LAM), a cell wall component of mycobacteria, can be detected in the urine of tuberculosis (TB) patients. Advantages of this diagnostic include the ease of sample collection and test methods. However, as with most new TB diagnostics, LAM tests have been evaluated in well-controlled laboratory settings and subsequently need assessment under real working conditions. Our experience showed that the diagnosis of TB using the detection of LAM in urine under fi eld conditions is prone to false-positive results due to contamination. Dust and soil, but also stool, seemed to lead to increased OD values and thus false-positive results of the enzyme-linked immunosorbent assay (ELISA) for LAM; however, contamination with blood, as well as bacterial or fungal organisms, had no infl uence. The collection of urine for the detection of LAM should therefore follow strict collection criteria in order to avoid contamination.

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“…used plasma samples that had been frozen, shipped and stored, whereas RDTs, while often validated for serum and plasma, are designed to be used with fresh specimens, typically capillary whole blood. While the limited data available do not indicate clear discordance with the testing results from previously frozen samples, as noted by the authors, “some studies have shown differences in sensitivity and specificity when using plasma/serum compared to capillary whole blood,” which could be postulated to have had an impact on the results seen .…”

Section: Discussionmentioning

confidence: 93%

A Commitment to HIV Diagnostic Accuracy – a comment on “Towards more accurate HIV testing in sub‐Saharan Africa: a multi‐site evaluation of HIV RDTs and risk factors for false positives” and “HIV misdiagnosis in sub‐Saharan Africa: a performance of diagnostic algorithms at six testing sites”

et al. 2018

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As part of the global response to the HIV/AIDS epidemic, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) is committed to the provision of high‐quality services and ensuring testing accuracy. Two recently published papers focusing on HIV testing and misdiagnosis in sub‐Saharan Africa by Kosack et al. report on evaluations of HIV rapid diagnostic tests (RDTs) and found lower than expected specificity and sensitivity on some tests when used in certain geographic locations. The magnitude of PEPFAR's global HIV response has been possible due to the extensive use of RDTs, which have made HIV diagnosis accessible all over the world. We take the opportunity to address concerns raised about the potential implications that these findings could have on real‐world HIV testing accuracy. PEPFAR supported countries adhere to the normative guidance by World Health Organization (WHO) supporting algorithms which require sequential positive tests for diagnostic accuracy. An analysis of Médecins Sans Frontières (MSF) RDT site‐specific data applied to PEPFAR in‐country protocols demonstrate a variation in the diagnostic accuracy of the testing algorithms, but with a very small population‐level effect. The data demonstrate, with the use of these algorithms, that the RDT outcomes found in the study by Kosack et al. would be largely mitigated and would not be expected to have a significant impact on diagnostic accuracy and overall programming in most countries. Avoiding any misdiagnosis is a priority for PEPFAR, and it remains vital to gain a deeper understanding of the causes and the extent of diagnostic errors and any misclassification. Extensive quality control mechanisms and continued research are essential. With a focus on epidemic control and ensuring diagnostic accuracy, PEPFAR recommends that all countries use WHO pre‐qualified RDTs within the recommended strategies and algorithms for HIV testing. We also support validation of HIV testing algorithms using in‐country specimens to determine optimal performance, and the reverification testing of all people diagnosed with HIV prior to starting treatment as an essential quality assurance measure.

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Low Specificity of Determine HIV1/2 RDT Using Whole Blood in South West Tanzania

Cited by 28 publications

References 20 publications

Evaluation of HIV testing algorithms in Ethiopia: the role of the tie-breaker algorithm and weakly reacting test lines in contributing to a high rate of false positive HIV diagnoses

Evaluation of HIV testing algorithms in Ethiopia: the role of the tie-breaker algorithm and weakly reacting test lines in contributing to a high rate of false positive HIV diagnoses

Reasons for false-positive lipoarabinomannan ELISA results in a Tanzanian population

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