Dilution testing using rapid diagnostic tests in a HIV diagnostic algorithm: a novel alternative for confirmation testing in resource limited settings

Leslie Shanks, M Ruby Siddiqui, Almaz Abebe, Erwan Piriou, Neil Pearce, Cono Ariti, Johnson Masiga, Libsework Muluneh, Joseph Wazome, Koert Ritmeijer, Derryck Klarkowski, Leslie Shanks, M Ruby Siddiqui, Almaz Abebe, Erwan Piriou, Neil Pearce, Cono Ariti, Johnson Masiga, Libsework Muluneh, Joseph Wazome, Koert Ritmeijer, Derryck Klarkowski

Abstract

Background: Current WHO testing guidelines for resource limited settings diagnose HIV on the basis of screening tests without a confirmation test due to cost constraints. This leads to a potential risk of false positive HIV diagnosis. In this paper, we evaluate the dilution test, a novel method for confirmation testing, which is simple, rapid, and low cost. The principle of the dilution test is to alter the sensitivity of a rapid diagnostic test (RDT) by dilution of the sample, in order to screen out the cross reacting antibodies responsible for falsely positive RDT results.

Methods: Participants were recruited from two testing centres in Ethiopia where a tiebreaker algorithm using 3 different RDTs in series is used to diagnose HIV. All samples positive on the initial screening RDT and every 10th negative sample underwent testing with the gold standard and dilution test. Dilution testing was performed using Determine™ rapid diagnostic test at 6 different dilutions. Results were compared to the gold standard of Western Blot; where Western Blot was indeterminate, PCR testing determined the final result.

Results: 2895 samples were recruited to the study. 247 were positive for a prevalence of 8.5 % (247/2895). A total of 495 samples underwent dilution testing. The RDT diagnostic algorithm misclassified 18 samples as positive. Dilution at the level of 1/160 was able to correctly identify all these 18 false positives, but at a cost of a single false negative result (sensitivity 99.6 %, 95 % CI 97.8-100; specificity 100 %, 95 % CI: 98.5-100). Concordance between the gold standard and the 1/160 dilution strength was 99.8 %.

Conclusion: This study provides proof of concept for a new, low cost method of confirming HIV diagnosis in resource-limited settings. It has potential for use as a supplementary test in a confirmatory algorithm, whereby double positive RDT results undergo dilution testing, with positive results confirming HIV infection. Negative results require nucleic acid testing to rule out false negative results due to seroconversion or misclassification by the lower sensitivity dilution test. Further research is needed to determine if these results can be replicated in other settings.

Trial registration: ClinicalTrials.gov, NCT01716299 .

References

    1. World Health Organization . Service delivery approaches to HIV testing and Counselling (HTC) Geneva: WHO; 2012.
    1. Gray RH, Makumbi F, Serwadda D, Lutalo T, Nalugoda F, Opendi P, et al. Limitations of rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study. BMJ. 2007;335(7612):188. doi: 10.1136/.
    1. Klarkowski DB, Wazome JM, Lokuge KM, Shanks L, Mills CF, O’Brien DP. The evaluation of a rapid in situ HIV confirmation test in a programme with a high failure rate of the WHO HIV two-test diagnostic algorithm. PLoS One. 2009;4(2):e4351. doi: 10.1371/journal.pone.0004351.
    1. Galiwango RM, Musoke R, Lubyayi L, Ssekubugu R, Kalibbala S, Ssekweyama V, et al. Evaluation of current rapid HIV test algorithms in Rakai, Uganda. J Virol Methods. 2013;192:25–7. doi: 10.1016/j.jviromet.2013.04.003.
    1. Aghokeng AF, Mpoudi-Ngole E, Dimodi H, Atem-Tambe A, Tongo M, Butel C, et al. Inaccurate diagnosis of HIV-1 Group M and O is a key challenge for ongoing universal access to antiretroviral treatment and HIV prevention in Cameroon. PLoS One. 2009;4(11) doi: 10.1371/journal.pone.0007702.
    1. Klarkowski D, O’Brien DP, Shanks L, Singh KP. Causes of false positive HIV rapid diagnostic test results. Expert Rev Anti Infect Ther. 2013;12(1):49–62. doi: 10.1586/14787210.2014.866516.
    1. Clinical and Laboratory Standards Institute (CLSI). Criteria for Laboratory Test-ing and Diagnosis of Human Immunodeficiency Virus Infection; Approved Guideline. CLSI document M53-A (ISBN 1-56238-757-X [Print]; ISBN 1-56238-758-8 [Electronic]); 2011.
    1. Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. Available at . Published June 27, 2014. Accessed [August 14, 2014].
    1. 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;15:39. doi: 10.1186/s12879-015-0769-3.
    1. Shanks L, Klarkowski D, O'Brien DP. False positive HIV diagnoses in resource limited settings: operational lessons learned for HIV programmes. PLoS One. 2013;8:e59906. doi: 10.1371/journal.pone.0059906.
    1. Department of Health and Human Services/Centre for Disease Control and Prevention/African Regional Office of the World Health Organization. Guidelines for Appropriate Evaluations of HIV Testing Technologies in Africa. 2002.
    1. Sandler SG, Dodd RY, Fang CT. Diagnostic tests for HIV infection: serology. In: De Vita VT, Hellman S, Rosenberg SA, editors. AIDS: etiology, treatment, and prevention. 2. Philadelphia: J.B. Lippincott; 1988. pp. 121–6.
    1. Pandori MW, Westheimer E, Gay C, Moss N, Fu J, Hightow-Weidman LB, et al. The Multispot rapid HIV-1/HIV-2 differentiation assay is comparable with the Western blot and an immunofluorescence assay at confirming HIV infection in a prospective study in three regions of theUnited States. J Clin Virol. 2013;58(Suppl 1):e92–6. doi: 10.1016/j.jcv.2013.10.006.
    1. Malloch L, Kadivara K, Putzb J, Levett PN, Tang J, Hatchette TF, et al. Comparative evaluation of the Bio-Rad Geenius HIV-1/2 ConfirmatoryAssay and the Bio-Rad Multispot HIV-1/2 Rapid Test as an alternative differentiation assay for CLSI M53 algorithm-I. J Clin Virol. 2013;58S:e85–91. doi: 10.1016/j.jcv.2013.08.008.
    1. World Health Organization Technical Working Group on HIV Incidence Assays . When and how to use assays for recent infection to estimate HIV incidence at a population level. Geneva: WHO; 2011.
    1. Constantine NT, Sill AM, Jack N, Kreisel K, Edwards J, Cafarella T, et al. Improved classification of recent HIV-1 infection by employing a two-stage sensitive/less-sensitive test strategy. J Acquir Immune Defic Syndr. 2003;32:94–103. doi: 10.1097/00126334-200301010-00014.
    1. Soroka SD, Granade TC, Candal D, Parekh BS. Modification of rapid human immunodeficiency virus (HIV) antibody assay protocols for detecting recent HIV seroconversion. Clin Diagn Lab Immunol. 2005;12:918–21.
    1. Girardi SB, Egydio de Carvalho Barretob AM, Barretob CC, Proietti AB, Farias de Carvalhof SM, Loureiro P, et al. Evaluation of rapid tests for human immunodeficiency virus as a tool to detect recent seroconversion. Braz J Infect Dis. 2012;16(5):452–6. doi: 10.1016/j.bjid.2012.08.013.
    1. Kshatriya R, Cachafeiro AA, Kerr RJS, Nelson JAE, Fiscus SA. Comparison of two rapid Human Immunodeficiency Virus (HIV) assays, determine™ HIV-1/2 and OraQuick advance rapid HIV-1/2, for detection of recent HIV Seroconversion. J Clin Microbiol. 2008;46(10):3482–3. doi: 10.1128/JCM.00665-08.
    1. Bouillon M, Aubin E, Roberge C, Bazin R, Lemieux R. Reduced frequency of blood donors with false-positive HIV-1 and −2 antibody EIA reactivity after elution of low-affinity nonspecific natural antibodies. Transfusion. 2002;42(8):1046–52. doi: 10.1046/j.1537-2995.2002.00164.x.
    1. Urwijitaroon Y, Barusrux S, Romphruk A, Puapairoj C, Thongkrajai P. Anti-HIV antibody titer: an alternative supplementary test for diagnosis of HIV-1 infection. Asian Pac J Allergy Immunol. 1997;15:193–8.
    1. Duedu KO, Hayford AA, Sagoe KW. Misclassification of recent HIV-1 seroconversion in sub-Saharan Africa using the sensitive/less sensitive technique. Virol J. 2011;8:176. doi: 10.1186/1743-422X-8-176.
    1. Hahn JA, Wanyenze RK. Potential for false positive HIV test results with the serial rapid HIV testing algorithm. BMC Res Notes. 2012;5:154. doi: 10.1186/1756-0500-5-154.
    1. Boeras D, 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;14:18. doi: 10.1186/1758-2652-14-18.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj