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”

Abstract

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.

Cost implications of HIV retesting for verification in Africa

“…And, retesting can rule out possible technical or clerical errors, including specimen mix-up through mislabeling and transcription errors, as well as random error by either the provider or the test device, though retesting for verification will not exclude misdiagnosis related to poor choice of a testing algorithm or cross-reactivity[18]. However, this risk should be reduced assuming the testing algorithm used is validated[20, 69, 70]. The WHO recommends following the approved national HIV testing algorithm and ensuring adherence to a quality-testing program with continuous quality assurance.…”

Rapid Diagnostic Tests for Trypanosoma cruzi Infection: Field Evaluation of Two Registered Kits in a Region of Endemicity and a Region of Nonendemicity in Argentina

“…Analytical validation of the manufacturers is usually performed with serum panels from people that do not always coincide with the target population. These serum panels are from populations who may not have diversity in the antigenic exposure ( T. cruzi strains), variations in population genetic bases of immune response, cross-reactivity with other prevalent infections, or differences in the samples used ( 28 , 29 ). For this reason, prior to the implementation of an RDT in the routine protocols, it is recommended to perform a verification study of the parameters indicated by the manufacturer in the target population.…”

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

“…The recommendation for verification of HIV status before ART initiation has been increasingly adopted to ensure the fidelity of the HIV testing and ART programmes and avoid future costs and ramifications associated with inadvertently initiating HIV‐negative persons on lifelong ART. Previous studies have highlighted that retesting may be particularly important considering reports of poor quality testing and low uptake of WHO‐recommended HIV testing strategies and algorithms . Policy analysis from 2015 suggested fewer than 20% of reporting countries had a national testing strategy and algorithm that was in full alignment with WHO guidelines .…”

“…These efforts combined with updated guidelines and re‐training of testers, decreased HIV‐negative test results following an initial HIV‐positive diagnosis from 7% to 1% between 2014 and 2016 . Additional studies have highlighted the role of retesting, alongside validation of national algorithms, to ensure quality .…”