Accuracy of serological assays for detection of recent infection with HIV and estimation of population incidence: a systematic review

Guy, Rebecca; Gold, Judy; Calleja, Jesus Maria Garcia; Kim, Andrea A; Parekh, Bharat; Busch, Michael P.; Rehle, T.; Hargrove, John W.; Remis, Robert S.; Kaldor, John

doi:10.1016/s1473-3099(09)70300-7

Cited by 118 publications

(128 citation statements)

References 42 publications

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“…[24][25][26][27][28][29][30] As would be appropriate in the more familiar diagnostic applications, values close to 100% have been regarded as realistic targets, with these two measures summarized into, for example, receiver operating characteristic (ROC) curves and the overall classification accuracy. This line of thinking runs into three major obstacles.…”

Section: Optimal Tests For Recent Infectionmentioning

confidence: 99%

Short Communication: Defining Optimality of a Test for Recent Infection for HIV Incidence Surveillance

Kassanjee

McWalter²,

Welte³

2014

AIDS Research and Human Retroviruses

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The estimation of HIV incidence from cross-sectional surveys using tests for recent infection has attracted much interest. It is increasingly recognized that the lack of high performance recent infection tests is hindering the implementation of this surveillance approach. With growing funding opportunities, test developers are currently trying to fill this gap. However, there is a lack of consensus and clear guidance for developers on the evaluation and optimization of candidate tests. A fundamental shift from conventional thinking about test performance is needed: away from metrics relevant in typical public health settings where the detection of a condition in individuals is of primary interest (sensitivity, specificity, and predictive values) and toward metrics that are appropriate when estimating a population-level parameter such as incidence (accuracy and precision). The inappropriate use of individual-level diagnostics performance measures could lead to spurious assessments and suboptimal designs of tests for incidence estimation. In some contexts, such as population-level application to HIV incidence, bias of estimates is essentially negligible, and all that remains is the maximization of precision. The maximization of the precision of incidence estimates provides a completely general criterion for test developers to assess and optimize test designs. Summarizing the test dynamics into the properties relevant for incidence estimation, high precision estimates are obtained when (1) the mean duration of recent infection is large, and (2) the false-recent rate is small. The optimal trade-off between these two test properties will produce the highest precision, and therefore the most epidemiologically useful incidence estimates. T he measurement of HIV incidence, the rate of new infections, is essential in most surveillance and intervention contexts. Recognizing the practical challenges presented by longitudinal studies, the estimation of incidence from cross-sectional surveys using tests for recent infection has attracted considerable interest.1-7 However, the performance, characterization, and optimization of a test that aims to categorize infections as ''recent'' or ''nonrecent,'' specifically for population-level surveillance, requires a shift from conventional diagnostic thinking about test performance.When individual-level detection of a condition is of primary interest, sensitivity, specificity, and predictive values are appropriate metrics of performance. These metrics improve as intersubject variability decreases. However, when estimating a population-level summary parameter, such as incidence, the appropriate performance metrics are accuracy and precision of the statistic measured. Biomarker-based cross-sectional incidence estimation utilizes information on the average behavior of biomarkers, and is relatively insensitive to the variability underlying this averaging. While the appropriate optimization of tests for recent infection has been noted in passing, [3][4][5][6][7] there is neither co...

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Section: Optimal Tests For Recent Infectionmentioning

confidence: 99%

Short Communication: Defining Optimality of a Test for Recent Infection for HIV Incidence Surveillance

Kassanjee

McWalter²,

Welte³

2014

AIDS Research and Human Retroviruses

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“…Consequently, there is always a certain degree of uncertainty associated with these assays. When the accuracy of incidence tests were systematically reviewed from published reports, sensitivity estimates ranged from 42 to 100% (89% overall median) for incident infections and specificity estimates ranged from 35 to 100% (98% overall median) for long-standing, nonincident infections [54].…”

Section: Estimating Incident Infection Ratesmentioning

confidence: 99%

“…future science group HIV diagnostics: challenges & opportunities | PersPective Furthermore, when assay-derived population incidence estimates were aggregated and compared with reference estimates, the differences ranged from 0 to 483% (median difference of 26%) [54]. Although these data do suggest that, at present, incidence testing may not be very accurate, especially in regions with diverse HIV populations such as Africa [55], STARHS methodologies can produce more reliable data if stakeholders take the opportunity to work together to establish standards for calculating cut-off values, algorithms for using multiple assays in concert to improve accuracy, and a framework for comparing different assays.…”

Section: Estimating Incident Infection Ratesmentioning

confidence: 99%

HIV Diagnostics: Challenges and Opportunities

Wong

Hewlett

2010

HIV Ther.

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Accurate HIV diagnostic testing continues to pose challenges, but there are also opportunities for assay performance improvements in key areas for specific intended-use settings. The genetic diversity of HIV can result in false and discordant results in assays that fail to detect new variant strains. The use of antiretroviral therapies has resulted in drug-resistant variants that require monitoring by sequencing and genotyping methods. Nucleic acid testing is the most sensitive and reliable platform for detection, but it is costly and limited to centralized testing facilities, making implementation difficult in resource-limited settings where HIV has hit the hardest. Rapid antibody tests suitable for point-of-care use are becoming more accessible in resource-limited settings, but these tests may not detect HIV during the acute infection stage. Emerging antigen/antibody combination assays are viable alternatives to nucleic acid testing for diagnosis of recent infections. Although patient monitoring (e.g., via CD4+ T-cell count and viral load determination) and infant diagnoses still rely on clinical laboratory-based testing, point-of-care options are being developed. There are other technical challenges to HIV diagnostic testing and emerging biodetection technologies that may be able to address them, but they are not yet proven.

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“…However, since the first assay-based method for estimating HIV incidence was proposed in 1995 (4), numerous serologic approaches based on the characteristics of HIV-specific antibody response maturation have not been satisfactory (5)(6)(7)(8). It has been reported that the serologic assays were overly dependent on the infecting virus subtype and displayed a substantial false-recency rate, which resulted in the overestimation of HIV incidence (2,3,7,9). Overall, the sensitivity-the proportion of incident infections correctly classified as incident-was 89% and the specificity-the proportion of chronic infections correctly identified as chronic-was 87% across 13 serologic assays (9).…”

mentioning

confidence: 99%

“…It has been reported that the serologic assays were overly dependent on the infecting virus subtype and displayed a substantial false-recency rate, which resulted in the overestimation of HIV incidence (2,3,7,9). Overall, the sensitivity-the proportion of incident infections correctly classified as incident-was 89% and the specificity-the proportion of chronic infections correctly identified as chronic-was 87% across 13 serologic assays (9). Recently, a new limiting antigen avidity assay has demonstrated a significantly lower false-recency rate than the current standard, the BED assay (10), among individuals with AIDS (0.2% versus 2.9%) (11).…”

mentioning

confidence: 99%

Developing High-Throughput HIV Incidence Assay with Pyrosequencing Platform

Park

Goeken

Lee

et al. 2014

J Virol

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Human immunodeficiency virus (HIV) incidence is an important measure for monitoring the epidemic and evaluating the efficacy of intervention and prevention trials. This study developed a high-throughput, single-measure incidence assay by implementing a pyrosequencing platform. We devised a signal-masking bioinformatics pipeline, which yielded a process error rate of 5.8 ؋ 10 ؊4 per base. The pipeline was then applied to analyze 18,434 envelope gene segments (HXB2 7212 to 7601) obtained from 12 incident and 24 chronic patients who had documented HIV-negative and/or -positive tests. The pyrosequencing data were cross-checked by using the single-genome-amplification (SGA) method to independently obtain 302 sequences from 13 patients. Using two genomic biomarkers that probe for the presence of similar sequences, the pyrosequencing platform correctly classified all 12 incident subjects (100% sensitivity) and 23 of 24 chronic subjects (96% specificity). One misclassified subject's chronic infection was correctly classified by conducting the same analysis with SGA data. The biomarkers were statistically associated across the two platforms, suggesting the assay's reproducibility and robustness. Sampling simulations showed that the biomarkers were tolerant of sequencing errors and template resampling, two factors most likely to affect the accuracy of pyrosequencing results. We observed comparable biomarker scores between AIDS and non-AIDS chronic patients (multivariate analysis of variance [MANOVA], P ‫؍‬ 0.12), indicating that the stage of HIV disease itself does not affect the classification scheme. The highthroughput genomic HIV incidence marks a significant step toward determining incidence from a single measure in cross-sectional surveys. IMPORTANCEAnnual HIV incidence, the number of newly infected individuals within a year, is the key measure of monitoring the epidemic's rise and decline. Developing reliable assays differentiating recent from chronic infections has been a long-standing quest in the HIV community. Over the past 15 years, these assays have traditionally measured various HIV-specific antibodies, but recent technological advancements have expanded the diversity of proposed accurate, user-friendly, and financially viable tools. Here we designed a high-throughput genomic HIV incidence assay based on the signature imprinted in the HIV gene sequence population. By combining next-generation sequencing techniques with bioinformatics analysis, we demonstrated that genomic fingerprints are capable of distinguishing recently infected patients from chronically infected patients with high precision. Our high-throughput platform is expected to allow us to process many patients' samples from a single experiment, permitting the assay to be cost-effective for routine surveillance.

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Accuracy of serological assays for detection of recent infection with HIV and estimation of population incidence: a systematic review

Cited by 118 publications

References 42 publications

Short Communication: Defining Optimality of a Test for Recent Infection for HIV Incidence Surveillance

Short Communication: Defining Optimality of a Test for Recent Infection for HIV Incidence Surveillance

HIV Diagnostics: Challenges and Opportunities

Developing High-Throughput HIV Incidence Assay with Pyrosequencing Platform

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