Point-of-Care Diagnostics for Acute HIV Infection: An Important Public Health Priority

Abstract

To the Editor—We appreciate the correspondence in this issue of the Journal by Jones et al and Laperche et al evaluating the performance of the Alere Determine HIV-1/2 Ag/Ab Combo test (Combo point-of-care test [POCT]) for the detection of antibodies for established human immunodeficiency virus (HIV) infection and p24 antigen for acute HIV infection (AHI) [1, 2]. We believe that the earliest stages of HIV infection, including AHI, are critical for both individual health and HIV prevention. During AHI, establishment of latency currently renders HIV infection incurable. Persons with AHI also have high viral loads, making them highly contagious for a brief period. AHI therefore represents an important time for intervention [3]. Identification of subjects with AHI is critical, yet challenging. Since persons are antibody-negative during AHI, HIV rapid tests, which detect HIV antibodies, cannot detect AHI. AHI can be detected only with diagnostics capable of identifying HIV RNA, DNA or p24 antigen. To date, most of these diagnostics have been laboratory-based. In a recent issue of the Journal, we evaluated the Combo POCT, a test designed to concomitantly detect HIV antibodies and p24 antigen in separate reading frames at the point of care [4]. Our study was conducted among persons attending a sexually transmitted infection clinic and an HIV testing and counseling center in Lilongwe, Malawi. We found that the antibody portion of the test had excellent sensitivity and specificity for detecting established HIV infection. However, the antigen portion of the test had zero sensitivity and inadequate specificity for detecting AHI. The antigen portion of the test was unable to identify any of the 8 persons with true AHI, and it falsely classified 6 HIV-uninfected persons as having AHI. Such incorrect results could cause considerable mental anguish, confusion, and cost. Jones et al report similar findings among high-risk persons in the United Kingdom [1]. The antibody portion of the Combo POCT had excellent sensitivity and specificity, but the antigen portion of the test had poor sensitivity and specificity. It did not identify the 2 persons with AHI, and it incorrectly classified 2 HIV-uninfected and 1 antibody-positive person as having AHI. They also noted several invalid tests and implementation challenges owing to a narrow reading interval. Laperche et al assess the sensitivity of the Combo POCT at different p24 concentrations and among different clades in archived plasma and stored supernatants [2]. Even in these laboratory settings, the Combo POCT was unable to detect p24 consistently, especially with non-B subtypes. Although laboratory testing can be an important early step for gauging when a test may or may not perform adequately, it simply cannot replace field testing, which is required to determine ultimate utility. This is especially important for a test like the Combo POCT, which is designed to be used at the point of care on finger-stick whole blood. Laperche et al note the difficulty of field testing for AHI. However, we and others have demonstrated the feasibility of this approach. We have reported elsewhere that AHI can be detected routinely in the sexually transmitted infection setting where we conducted our analysis [5], allowing us to conduct ongoing studies related to this stage of HIV disease [6–7]. Although the performance of the antigen portion of the Combo POCT has been disappointing, the goal of identifying persons during AHI is important [8]. Investigators and industry should work together toward designing sensitive and specific diagnostics that can detect AHI at the point of care. These diagnostics must then be field tested before clinical use, regardless of the degree of difficulty involved.