Background:  The US Centers for Disease Control and Prevention (CDC) recently recommended expanding HIV antibody testing. However, HIV nucleic acid amplification tests (NAAT) are more sensitive than antibody tests in acute and early infection, when persons are highly infectious.

Methods:  From September 2003 until June 2008, Public Health-Seattle and King County offered HIV antibody testing to men who have sex with men (MSM) using the OraQuick Advance Rapid HIV-1/2 Antibody Test (OraSure) on oral fluid or finger-stick blood specimens or using an enzyme immunoassay (EIA; Vironostika HIV-1 Microelisa System; bioMerieux) or Genetic Systems rLAV EIA (Bio-Rad). An EIA was used to confirm reactive rapid tests and to screen specimens from OraQuick-negative MSM prior to pooling for HIV NAAT. We used frozen sera from 16 EIA-negative/NAAT-positive MSM to evaluate the ability of the fourth generation ARCHITECT HIV Ag/Ab Combo assay (Abbott Diagnostics, not available for sale in the United States) to detect acute infection. HIV RNA levels were quantified using the Abbott RealTime HIV-1 assay.

Results:  Overall, 328 (2.3%) of 14,005 specimens were HIV EIA-positive, and 36 (0.3%) EIA-negative MSM tested NAAT-positive. Among the 6811 OraQuick-negative specimens, 16 (0.2%) HIV-infected MSM were EIA-reactive, and 23 (0.3%) EIA-negative MSM were diagnosed with acute HIV infection through pooled HIV NAAT. 14 of the 16 OraQuick-negative/EIA-reactive testers had positive Western Blot results, and most had evidence of early HIV infection. Among rapid testers, OraQuick detected only 153 (80%) of 192 HIV-infected MSM, and OraQuick plus an EIA detected 169 (88%) infections detected by the program. The ARCHITECT HIV Ag/Ab Combo assay detected 15 (94%) of 16 MSM with acute HIV infection who had a median HIV RNA level of 6.6 (IQR 5.8-6.9) log₁₀ copies/mL. The specimen with the non-reactive test had an HIV RNA level of 4.2 and 3.7 log₁₀ copies/mL by the real-time polymerase chain reaction (RT-PCR) and Abbott RealTime HIV-1 assays, respectively.

Conclusions:  OraQuick performed on oral fluids or finger-stick blood specimens may be less sensitive than early generation EIA. However, our findings may not be generalizable to populations with lower HIV prevalence and incidence. Nevertheless, HIV NAAT should be integrated into HIV testing programs serving MSM and other high-incidence populations with frequent HIV testing, particularly when rapid antibody testing is employed. Fourth-generation antigen-antibody combination assays may be a reasonably sensitive alternative to HIV NAAT.