HIV testing in a high-incidence population: is antibody testing alone good enough?

Abstract

Background: The Centers for Disease Control and Prevention recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing. However, antibody tests have longer "window periods" after HIV acquisition than do nucleic acid amplification tests (NAATs).

Methods: Public Health-Seattle & King County offered HIV antibody testing to men who have sex with men (MSM) using the OraQuick Advance Rapid HIV-1/2 Antibody Test (OraQuick; OraSure Technologies) on oral fluid or finger-stick blood specimens or using a first- or second-generation enzyme immunoassay. The enzyme immunoassay was also used to confirm reactive rapid test results and to screen specimens from OraQuick-negative MSM prior to pooling for HIV NAAT. Serum specimens obtained from subsets of HIV-infected persons were retrospectively evaluated by use of other HIV tests, including a fourth-generation antigen-antibody combination assay.

Results: From September 2003 through June 2008, a total of 328 (2.3%) of 14,005 specimens were HIV antibody positive, and 36 (0.3%) of 13,677 antibody-negative specimens were NAAT positive (indicating acute HIV infection). Among 6811 specimens obtained from MSM who were initially screened by rapid testing, OraQuick detected only 153 (91%) of 169 antibody-positive MSM and 80% of the 192 HIV-infected MSM detected by the HIV NAAT program. HIV was detected in serum samples obtained from 15 of 16 MSM with acute HIV infection that were retrospectively tested using the antigen-antibody combination assay.

Conclusions: OraQuick may be less sensitive than enzyme immunoassays during early HIV infection. NAAT should be integrated into HIV testing programs that serve populations that undergo frequent testing and that have high rates of HIV acquisition, particularly if rapid HIV antibody testing is employed. Antigen-antibody combination assays may be a reasonably sensitive alternative to HIV NAAT.

Figure 1

Testing algorithm for men who have sex with men (MSM) who sought human immunodeficiency virus (HIV) testing through Public Health–Seattle & King County (PHSKC)–funded sites. MSM who sought HIV testing through PHSKC-funded testing sites underwent different testing algorithms, depending on the location and calendar year. At the PHSKC sexually transmitted disease (STD) clinic, rapid HIV antibody testing is routinely offered only to high-risk MSM (i.e., men who report unprotected anal intercourse with partners who were HIV infected or of unknown serostatus, who have a bacterial sexually transmitted infection, or who have a history of methamphetamine or “popper” use in the prior year). After November 2005, after identification of the first MSM with a negative result of OraQuick Advance Rapid HIV-1/2 Antibody Test (OraQuick; OraSure Technologies) and positive result of an enzyme immunoassay (EIA), all OraQuick-negative specimens were screened using an EIA prior to pooling for HIV nucleic acid amplification test (NAAT).

Figure 2

Effect of frequency of testing among individuals newly infected with human immunodeficiency virus (HIV) on HIV test sensitivity. If the timing of testing is independent of the risk for HIV acquisition, and if HIV antibody and the nucleic acid amplification test (NAAT) detect all infections after the “window period,” yearly testing by HIV antibody and NAAT detect 91% and 96% of infections, respectively, that occur in the inter-test interval. Semi-annual testing intervals detect 84% and 93% of infections, and quarterly testing intervals detect 72% and 86% of infections that occur in the intertest interval. The actual rate of false-negative test results may increase or decrease if the timing of testing is not independent of risk—that is, if testing is prompted by a risky exposure and whether testing is delayed appropriately to account for the window period.