This article is available in: PDF HTML EPUB XML

Alert, but not alarmed - 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 (Kosack et al. 2017)”

Letter to the editor

Alert, but not alarmed - 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 (Kosack et al. 2017)”

Cheryl C. Johnson1,§, Anita Sands2, Willy Urassa2 and Rachel Baggaley1

§Corresponding author: Cheryl C Johnson, Department of HIV, World Health Organization, 20 Avenue Appia, Geneva 1201, Switzerland. Tel: +41 22 791 4335. (

Keywords HIV; diagnostic; test; quality; misdiagnosis; false positive; Africa

Received 28 April 2017; Accepted 2 June 2017; Published 19 June 2017

Copyright: © 2017 Johnson CC et al; licensee International AIDS Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Johnson CC et al. Journal of the International AIDS Society 2017, 20:22042 |

Dear Editors,

We read with interest Kosack and colleagues’ article [1], which evaluated eight HIV rapid diagnostic tests (RDTs) using specimens collected from Médecins Sans Frontières (MSF) sites, between 2011 and 2015, in five African countries. Authors state that RDT accuracy differed from previous evaluations conducted by the World Health Organization (WHO), concluding only one HIV RDT achieved WHO prequalification performance criteria and none met WHO performance thresholds when using the “lower end of the 95% CI”. Authors attributed such “poor performance”, primarily poor specificity, to the RDTs and possible non-specific geographical and population-level interferrents.

Overall, we agree with the author’s findings and their conclusions, which affirm WHO recommendations to use a validated testing algorithm. However, we do not agree with the author’s discussion, which is at odds with WHO’s data and suggests misdiagnosis of HIV occurred and can be attributed to WHO-prequalified RDTs. Given the limitations of the evidence presented, we find their discussion to be potentially misleading.

The authors report that they found a substantial number of false reactive test results resulting in poor positive predictive values. This finding is based on the result of a single HIV RDT. A single reactive test result is never sufficient to make an HIV-positive diagnosis. To provide a definitive HIV diagnosis, WHO recommends countries use a high (≥5%) or low (<5%) prevalence testing strategy comprised of up to three RDTs as part of a validated testing algorithm [2]. Thus, it is incorrect for the authors to discuss these findings in the context of “misdiagnosis”, as no evidence of actual misdiagnosis (false positive or false negative diagnoses) is presented. In fact, while not noted by the authors, if all study sites used the data from Table 2 and adhered to WHO recommendations, all settings could construct a highly accurate testing algorithm and thereby provide highly accurate HIV diagnoses.

While the authors acknowledge that some studies have found HIV RDT performance, particularly specificity, to vary across populations and settings due to cross-reacting antibodies [39], they state that their study relied on self-reported morbidities and did not find a significant association with false reactive results. However, Table 7 suggests that self-reported “malaria” was associated with false reactive test results on one RDT (2.62, 95% confidence interval [CI]: 1.215.6). In the absence of a review of clinical records and patient information, it is not known what other morbidities or factors may have contributed to these results. Authors also did not provide details on the sites where the specimens were collected, or the testing algorithms used at each site. Without knowing the testing algorithms, it is not known if the specimens were characterized correctly.

Between 2011 and 2015 it is known that some of the study countries utilized a “tiebreaker” approach to resolve discrepant test results and rule in HIV infection, instead of considering these results as “inconclusive” and retesting patients in 14 days as recommended by WHO [2]. Previous studies have demonstrated this to be a possible cause of false positive results and misdiagnoses [1018]. Thus, if these suboptimal testing strategies were used at site level, the study may have included “inconclusive” specimens that were misclassified as “HIV-positive” specimens. This could explain the high proportion of false reactive results observed.

Lastly, although the authors report this as a systematic head-to-head evaluation, it should be clarified that this study did not conduct a systematic head-to-head comparison of MSF and WHO evaluations. Authors do not discuss methodological differences between WHO performance evaluations and those presented by the authors; namely that WHO evaluations are conducted using specimens collected worldwide. WHO performance criteria are based on RDTs achieving ≥99% sensitivity and ≥98% specificity as a fixed proportion because characterized HIV-positive and HIV-negative specimens are used [19]. Using a 95% CI is only relevant if one is making an inference to the population where the specimens originated and the true HIV status of the specimens is unknown. Therefore, using the lower end of the 95% CI as a point of comparison between WHO and MSF evaluations is irrelevant and misleading.

This study presents important results and affirms the importance of using a validated testing algorithm, as recommended by WHO. While we concur with their conclusion, the author’s discussion points are not supported by the evidence in this article. Authors should reconsider their remarks or provide evidence indicating actual misdiagnosis, attributable to RDT performance alone.

This evidence should be viewed in the broader context of HIV diagnosis. Countries must be advised that WHO-prequalified HIV RDTs are accurate and can be used to provide a reliable HIV diagnosis. Nevertheless, countries and programmes need to ensure that they are following WHO-recommended HIV testing strategies and use a validated testing algorithm.

Authors affiliations

1Department of HIV, World Health Organization, Geneva, Switzerland; 2Department of Essential Medicines and Health Products, World Health Organization, Geneva, Switzerland

Competing interests

We declare no competing interests. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.

Authors contribution

CJ and RB conceived of the letter. CJ drafted the initial letter with input from RB, WU and AS. All authors have contributed to developing the letter.


We would like to thank Buhle Ncube, Christine Kisia, Rita Nalwadda, Gottfried Hirnschall, Deusdedit Mubangizi, Suzanne Hill and Emer Cooke for their review and input into developing this letter.



Kosack CS, Page A-L, Beelaert G, Benson T, Savane A, Ng’ang’a A, et al. Towards more accurate HIV testing in sub-Saharan Africa: a multi-site evaluation of HIV RDTs and risk factors for false positives. J Int AIDS Soc. 2017;19(1):12.


World Health Organization (WHO). Consolidated guidelines on HIV testing services. Geneva: World Health Organization; 2015. Available from:


Lejon V, Ngoyi DM, Ilunga M, Beelaert G, Maes I, Buscher P, et al. Low specificities of HIV diagnostic tests caused by Trypanosoma brucei gambiense sleeping sickness. J Clin Mic. 2010;48(8):28369.


Esteva MH, Blasini AM, Ogly D, Rodriguez MA. False positive results for antibody to HIV in two men with systemic lupus erythematosus. Ann Rheum. 1992;51(9):10713.


Riberio T, Brites C, Moreira EJ, Siller K, Silva NJ, Johnson WD Jr, et al. Serologic validation of HIV infection in a tropical area. JAIDS. 1993;6(3):31922.


Everett DB, Baisely KJ, McNerney R, Hambleton I, Chirwa T, Ross DA, et al. Association of schistosomiasis with false-positive HIV test results in an African adolescent population. J Clin Mic. 2010;48(5):15707.


Salinas A, Górgolas M, Fernández-Guerrero M. Refrain from telling bad news: patients with leishmaniasis can have false-positive HIV test results. Clin Inf Dis. 2007;45(1):13940.


Klarkowski D, Glass K, O’Brien D, Lokuge K, Piriou E, Shanks L. Variation in specificity of HIV rapid diagnostic tests over place and time: an analysis of discordancy data using a Bayesian approach. PLoS ONE. 2013;8(11):e81656.


Klarkowski D, O’Brien DP, Shanks L, Singh KP. Causes of false-positive HIV rapid diagnostic test results. Expert Rev Anti Infect Ther. 2014;12(1):4962.


World Health Organization (WHO). Annex 14. A report on the misdiagnosis of HIV status. Geneva: World Health Organization; 2015. Available from:


Shanks L, Ritmeijer K, Piriou E, Siddiqui MR, Kliescikova J, Pearce N, et al. Accounting for false positive HIV tests: is visceral leishmaniasis responsible? PLoS ONE. 2015;10(7):e0132422.


Baveewo S, Kamya MR, Mayanja-Kizza H, Fatch R, Bangsberg DR, Coates T, et al. Potential for false positive HIV test results with the serial rapid HIV testing algorithm. BMC Res Notes. 2012;5:154.


da Costa Ferreira Junior O, Ferreira C, Riedel M, Visinoni W, Sasazawa I, Westman S, et al. Field evaluation of an HIV rapid test algorithm for the rapid diagnosis of HIV infection in Brazil. Presented at: HIV Pathogenesis, Treatment and Prevention; 2007 July 2225; Sydney, Australia.


Eller LA, Eller MA, Ouma BJ, Kataaha P, Bagaya BS, Olemukan RL, et al. Large-scale human immunodeficiency virus rapid test evaluation in a low-prevalence Ugandan blood bank population. J Clin Mic. 2007;45(10):32815.


Jentsch U, Lunga P, Lacey C, Weber J, Cairns J, Pinheiro G, et al. The implementation and appraisal of a novel confirmatory HIV-1 testing algorithm in the microbicides development programme 301 trial (MDP301). PLoS ONE. 2012;7(9):e42322.


Boeras DI, Luisi N, Karita E, McKinney S, Sharkey T, Keeling M, et al. Indeterminate and discrepant rapid HIV test results in couples’ HIV testing and counselling centres in Africa. J Int AIDS Soc. 2011;14(1):18.


Crucitti T, Taylor D, Beelaert G, Fransen K, Van Damme L. Performance of a rapid and simple HIV testing algorithm in a multicenter phase III microbicide clinical trial. Clin Vaccine Immunol. 2011;18(9):14805.


Shanks L, Siddiqui MR, Kliescikova J, Pearce N, Ariti C, Muluneh L, et al. 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. BMC Infect Dis. 2015;15(1):39.


World Health Organization (WHO). Selecting and purchasing HIV, HBsAg and HCV in vitro diagnostics. Geneva: World Health Organization. [cited 2017 Apr 22]. Available from:

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Journal of the International AIDS Society | eISSN 1758-2652 | Editors-in-Chief: Susan Kippax and Kenneth Mayer

*2016 Journal Citation Reports® Science Edition - a Clarivate Analytics product.

Disclaimer: The Journal of the International AIDS Society is an official journal of and is published by the International AIDS Society. The costs of the Journal of the International AIDS Society are secured by the International AIDS Society. This support does not in any way affect the editorial independency of the Journal of the International AIDS Society. Material published in the journal is entirely independent of the opinion of external sponsors and the society.