Misdiagnosis of HIV infection during a South African community‐based survey: implications for rapid HIV testing

Abstract

Introduction: We describe the overall accuracy and performance of a serial rapid HIV testing algorithm used in community-based HIV testing in the context of a population-based household survey conducted in two sub-districts of uMgungundlovu district, KwaZulu-Natal, South Africa, against reference fourth-generation HIV-1/2 antibody and p24 antigen combination immunoassays. We discuss implications of the findings on rapid HIV testing programmes. Methods: Cross-sectional design: Following enrolment into the survey, questionnaires were administered to eligible and consenting participants in order to obtain demographic and HIV-related data. Peripheral blood samples were collected for HIV-related testing. Participants were offered community-based HIV testing in the home by trained field workers using a serial algorithm with two rapid diagnostic tests (RDTs) in series. In the laboratory, reference HIV testing was conducted using two fourth-generation immunoassays with all positives in the confirmatory test considered true positives. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value and false-positive and false-negative rates were determined. Results: Of 10,236 individuals enrolled in the survey, 3740 were tested in the home (median age 24 years (interquartile range 19–31 years), 42.1% males and HIV positivity on RDT algorithm 8.0%). From those tested, 3729 (99.7%) had a definitive RDT result as well as a laboratory immunoassay result. The overall accuracy of the RDT when compared to the fourth-generation immunoassays was 98.8% (95% confidence interval (CI) 98.5–99.2). The sensitivity, specificity, positive predictive value and negative predictive value were 91.1% (95% CI 87.5–93.7), 99.9% (95% CI 99.8–100), 99.3% (95% CI 97.4–99.8) and 99.1% (95% CI 98.8–99.4) respectively. The false-positive and false-negative rates were 0.06% (95% CI 0.01–0.24) and 8.9% (95% CI 6.3–12.53). Compared to true positives, false negatives were more likely to be recently infected on limited antigen avidity assay and to report antiretroviral therapy (ART) use. Conclusions: The overall accuracy of the RDT algorithm was high. However, there were few false positives, and the sensitivity was lower than expected with high false negatives, despite implementation of quality assurance measures. False negatives were associated with recent (early) infection and ART exposure. The RDT algorithm was able to correctly identify the majority of HIV infections in community-based HIV testing. Messaging on the potential for false positives and false negatives should be included in these programmes.

To err is human, to correct is public health: a systematic review examining poor quality testing and misdiagnosis of HIV status

“…Most studies were carried out in Africa ( n  = 48) [5,7,10–14,16,22–25,29,30,32–34,36,37,39,41,43,44,46,47,49,51,52,54–59,61–65,67–72,74,75], followed by in the Americas ( n  = 7) [28,31,42,50,53,60,66], Asia ( n  = 4) [8,35,45,73] and Europe ( n  = 1) [48]. There were also four multi-country/regional studies [26,27,38,40].…”

“…Nine studies reported more than one unit of measure, and three studies did not specify sample size (see supplementary information). The majority of studies occurred in a facility-based setting; studies carried out in community settings included the workplace ( n  = 1) [57], home-based testing ( n  = 2) [14,39] and a mobile setting ( n  = 1) [32]. …”

“…Thirty-seven studies reported using a suboptimal testing strategy that differed from the WHO recommendations [5,8,11–14,16,22–30,32–34,36–39,42–44,49,51,53,59,62,64–66,68,72,75]. Suboptimal testing strategies included using a highly specific first-line test and highly sensitive second-line test [14,33,39,55], using a single RDT for HIV-positive diagnoses [11,66,72], using a high prevalence testing strategy in a low prevalence setting [16,49], using a parallel testing algorithms and a tiebreaker testing strategy (where a third assay is used to resolve discrepant test results and rule in HIV infection) [5,12,13,16,24,25,27–30,32,34,36,37,68].…”

“…Additionally, six studies reported that a proportion of false negative diagnoses were among people with a known HIV status who were on ART [14,16,39,44,47,58]; one of these studies was among children on ART retested using an oral fluid-based HIV RDT [58]. And three studies reported false negative results were due to patients testing in the window period [45] or with acute or early infection [16,44].…”

“…In general, error rates were small (median: 3.1%; IQR: 0.4%-5.2%) with the exception of a few studies where a tiebreaker test was used to resolve discrepant results [10–14,23,32,33,37,39,41,44,46,47,75] (Figure 2). Of these, six studies (eight reports) exclusively among people with HIV enrolled in care or ART reported that between 0.1% (95% CI: 0–0.3) and 6.6% (95% CI: 4.5–9.6) of people were misdiagnosed (median: 1.6%, IQR: 0.3–4.7%) [10–13,33,37,39,41,47] (Table 3).

Figure 2.Rates of false positive diagnostic error rates diagnosis ( n  = 30 studies, 43 reports).LP: low prevalence; HP: high prevalence; ZAM: Zambia; VL: visceral Leishmaniasis; Data reported include reports of misdiagnosis of HIV-positive statuses.

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