Improving the Quality of Diagnostic Studies Evaluating Point of Care Tests for Acute HIV Infections: Problems and Recommendations

Abstract

The diagnosis of acute human immunodeficiency virus (HIV) infection (AHI) plays a unique role in preventing the spread of HIV and ending the epidemic. Acutely infected individuals are thought to contribute substantially to forward transmissions of HIV; however, diagnosing AHI in resource-limited settings has proven to be a challenge. While fourth generation antigen-antibody combination assays have been successful in high-resource settings, rapid point of care (POC) versions of these assays have yet to demonstrate high sensitivity to detect AHI. Newer RNA/DNA based POC technologies are being validated, but the challenge to understand the additional value of these devices depends on the quality of study evaluations, in particular choice of study designs and case mix of included populations. In this commentary, we aimed to review the quality of studies evaluating a new fourth generation rapid test for detecting AHI, to identify general methodological limitations and biases in diagnostic accuracy studies, and to recommend strategies for avoiding them in future evaluations. The new studies that were evaluated continued to report the same weaknesses and biases that were seen in previous evaluations of fourth generation rapid tests. We recommend that investigators design future studies carefully, keeping in mind how diagnostic performance may be influenced by prevalence, population, patient case mixes, and reference standards. Care must be taken to avoid biases specific to diagnostic accuracy studies (spectrum, verification, incorporation and reference standard biases). To improve on quality, reporting checklists and guidelines such as Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Standards for Reporting Diagnostic accuracy studies (STARD) should be reviewed prior to conducting studies.

Development of an approach to monitor the manufacturing consistency of HIV rapid diagnostic tests: Panel qualification and potential impact on country programs

“…Rapid diagnostic tests (RDTs), also commonly referred to as rapid test kits (RTKs), for HIV diagnosis are vital to public health programs that commonly rely on multi-product algorithms, where a patient is tested with different products brands for confirmation [1][2][3][4][5]. Diagnostic accuracy is critical to ensure the resources for treatment are appropriately applied to all patients in need, thus emphasizing the importance for overall quality assurance of country programs [6] and for implementing improvements in existing programs [7]. Inaccurate or discordant results can occur for a variety of reasons.…”

Clinical signs and symptoms associated with acute HIV infection from an intensely monitored cohort on 2 continents

“…[3,13] The cost of individual testing of all at-risk individuals, especially with newer fourth generation tests, is prohibitively expensive in resource-limited settings. [14] The diagnosis of AHI is even delayed in settings that are not as constrained by finances, including highrisk patient populations. [15] Consequently, a better understanding of the clinical presentation of AHI and subsequent development of a scoring algorithm, particularly in high-risk groups in resource limited areas could assist in improving utilization of testing and earlier identification of cases.…”

“…Although nucleic acid amplification testing is a fundamental diagnostic tool for AHI, the technique remains expensive and the optimal use of these tests in an appropriate diagnostic strategy has yet to be defined [3,13] . The cost of individual testing of all at-risk individuals, especially with newer fourth generation tests, is prohibitively expensive in resource-limited settings [14] . The diagnosis of AHI is even delayed in settings that are not as constrained by finances, including high-risk patient populations [15] .…”