Real-world performance of the new US HIV testing algorithm in medical settings

Abstract

Background Our medical center laboratory recently adapted its 24/7, two-hourly testing program to use an ARCHITECT-Multispot-viral load (AR-MS-VL) algorithm in place of a previous rapid test-immunofluorescence (RT-IF) algorithm. Objectives We evaluated screening test performance, acute case detection, turnaround time and ability to resolve HIV status under the new algorithm. Study Design We considered consecutive HIV tests from January-November 2015. AR-MS-VL results at Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG) were compared with RT-IF results at ZSFG and also with AR-MS-VL results in the recently completed CDC Screening Targeted Populations to Interrupt On-going Chains of HIV Transmission with Enhanced Partner Notification (STOP) Study for targeted testing of MSM at publicly funded testing sites in San Francisco. Results Among 21,985 HIV tests performed at ZSFG, 16,467 were tested by RT-IF and 5,518 by AR-MS-VL. There were 321 HIV infections detected, of which 274 (84%) were known HIV+ cases, and 47 were newly identified HIV infections (prevalence 0.22%). Under the AR-MS-VL algorithm, turnaround times for screening and full algorithm results were 3 and 21 hours; status-unresolved cases were reduced (from 47% to 22%) compared with the RT-IF algorithm. The positive predictive value (PPV) of a new-positive AR screening test was low (0.44) at ZSFG, where no acute infections were detected. At STOP Study sites where acute infection was more common, the AR PPV was higher (0.93). All 24 false-positive AR screening tests at ZSFG had a signal/cutoff (S/CO) ratio of <15 and all 88 true-positive tests had S/CO ratio >15. Of 62 acute infections in the STOP Study, 23 (37%) had an S/CO<15. Discussion An AR-MS-VL algorithm is feasible and can return rapid results in a large medical center. In this setting, reactive 4th generation assay tests that are negative for HIV antibodies are typically false-positive with low S/CO ratios.

Clinical Utility of the Signal-to-Cutoff Ratio of Reactive HIV Antigen/Antibody Screening Tests in Guiding Emergency Physician Management

“…Although no single S/CO ratio can reliably distinguish a true-positive from a false-positive HIV antigen/antibody test, the S/CO ratio can serve as a valuable diagnostic tool, informing posttest probability of disease and influencing medical decision-making. 12,14,19–22 In fact, based on the S/CO ratio alone, 82% of the 1035 ED patients in our study with a reactive HIV antigen/antibody test could be classified with a high degree of diagnostic certainty: with 9% classified as being very unlikely to have HIV (S/CO < 1.58) and 73% classified as being very likely to have HIV (S/CO ≥ 20.7). This left only 18% of ED patients with a reactive HIV antigen/antibody test in a diagnostic grey area (those with S/CO ratios between 1.58 and 20.7) whose posttest probability of being HIV-positive was approximately 30%.…”

“…We demonstrated that ED patients with acute HIV infection, compared with those with chronic infection, tend to have lower S/CO ratios and that S/CO ratios in these lower ranges likely represent more recent HIV infection, a finding previously described in non-ED testing sites. 12,14,15,19,22 The S/CO ratio, however, cannot accurately distinguish between acute and chronic infections. Practically, this means EPs must consider acute HIV infection in every patient with a reactive HIV antigen/antibody test and pay particular attention to those with lower S/CO ratios by performing a focused clinical evaluation looking for signs and symptoms of acute HIV infection and recent HIV exposure.…”

“…11 The results of the Architect HIV antigen/ antibody test are expressed in units of chemiluminescence, defined as a signal-to-cutoff (S/CO) ratio, which is reported in the health record as either nonreactive (S/CO , 1.0) or reactive (S/CO $ 1.0). Several studies have suggested that the magnitude of a reactive S/CO ratio may be helpful in discriminating true-positive from false-positive HIV antigen/ antibody screening tests [12][13][14] and may be used clinically to guide the initiation of antiretroviral therapy (ART) in patients suspected of experiencing acute HIV infection, before the results of confirmatory tests are available. 15…”

A case of a false positive HIV antigen/antibody screen in a pregnant woman at delivery and the clinical importance of reviewing signal-to-cutoff ratio values

“…Many studies include a PPV for the screening test as well as a suggested S/Co ratio for optimal screening test performance. Study N = PPV Median S/Co ratio of True Positives (Range) Median S/Co ratio of False Positives (Range) Optimal S/Co ratio (100 % sensitivity maintained unless otherwise stated) Significance of difference in S/Co ratios Marson et al [12] 5518 44 % 15 (Low risk setting) Jensen et al [9] 138,911 69 % 328.3 (1.1–1493.6) 1.9 (1.0–151.17) P < 0.0001 Baltaro et al [4] 61,666 5 (100 when WBC > 6.5) Alonso et al [3] 69,471 91 % 660.74 (2.91–1392.12) 2.31 (1.02–130.36) 2.5 (ROC) P < 0.0001 Hodgson et al [8] 11,987 46 % 826 (199–1094) 2 (1–39) Ramos et al [15] 21,317 87 % 794 ≈ 2 Chavez et al [5] 10,995 411.9 2.9 Zhang et al [26] 692,155 79 % overall (46 % for female samples) 352.17 1.77 Males: 8.96 (ROC) Females: 26.97 (ROC) P < 0.05 White et al [21] 1035 reactive screens 78 % 539.2 (1.58–1867.6) 1.93 (1.0–363) 20.7 by ROC (sensitivity 93.2 %) P < 0.001 Cui et al ...…”

Risks of requiring a dedicated molecular specimen for HIV diagnosis and a potential strategy for mitigation

“…This builds upon the existing HIV testing algorithm to stratify patients as "presumptive HIV positive" versus "likely false-positive fourth-generation screening test" based upon the S/CO ratio generated by the fourth-generation test. Multiple studies, including ours, have demonstrated high sensitivity and specificity when a S/CO ratio of >10-15 is useful to predict true HIV positivity [5][6][7][8][9]. Our study is unique in that we examined this cutoff in the specific patient population in which follow-up testing is challenging, those with positive fourth generation tests and negative supplemental tests.…”