Alternative algorithms for human immunodeficiency virus infection diagnosis using tests that are licensed in the United States

Abstract

Serodiagnosis of human immunodeficiency virus (HIV) infection in the United States has traditionally relied on a sequential two-test algorithm: an initial screen with an enzyme immunoassay (EIA) and reflex testing of EIA-reactive specimens with a more specific supplemental test such as Western blotting or immunofluorescence. The supplemental tests are tedious, subjective, and expensive. In addition, there have been major improvements in the performance and accuracy of the EIA tests as well as the introduction of rapid serologic tests (RT) and HIV nucleic acid amplification tests (NAAT). Related to these improvements is the possibility that alternative algorithms using combinations of currently approved HIV tests may function as well as if not better than the current algorithm, with more flexibility, improved accuracy, and lower cost. To this end, we evaluated the performance of 12 currently licensed tests and 1 in-house HIV test (6 EIA, 4 RT, and 3 NAAT) on panels of plasma samples from HIV-infected (n = 621 HIV type 1 [HIV-1] and 34 HIV-2) and uninfected (n = 513) people and of sequential specimens from people early in seroconversion (183 specimens from 15 patients). Test combinations were analyzed in two dual-test (sensitivity-optimized and specificity-optimized) algorithms and in a three-test (tie-breaking) algorithm, and performance was compared to the conventional algorithm. The results indicate that alternative algorithm strategies with currently licensed tests compare favorably with the conventional algorithm in detecting and confirming established HIV infection. Furthermore, there was a lower frequency of discordant or indeterminate results that require follow-up testing, and there was improved detection of early infection.

FIG. 1.

Evolution of test reactivity during early HIV-1 infection. (a) Cumulative frequency of positive test results relative to the number of days before the Western blot was first positive. Serial specimens (n = 183) were collected during seroconversion from 15 donors and tested by the following tests: Procleix (▪), GS HIV-1/2 (□), Abbott (•), Reveal (○), indeterminate Western blotting (×), Multispot (▴), GS rLAV (▵), Oraquick (+), positive Western blotting (—-), Uni-Gold (⋄), and Vir HIV-1 (♦). (b) Sequence along timeline in which the indicated tests registered 50% of specimens positive. WB, Western blot.