Background:  Although rapid HIV tests increase the number of persons who are aware of their HIV status, the tests may have limited sensitivity for the diagnosis of early HIV infection, resulting in missed opportunities for HIV prevention. We evaluated the sensitivity for early HIV infection of several rapid tests and third and fourth generation assays compared with nucleic acid amplification testing (NAAT).

Methods:  In the CDC Acute HIV Infection study, persons underwent routine HIV antibody screening at 96 clinics in 3 US cities. Specimens that were negative or indeterminate by serologic testing underwent NAAT. To evaluate sensitivity for early HIV infection using NAAT as a gold standard, all NAAT-positive specimens underwent third generation testing with Genetic Systems 1/2 +O^® and rapid testing with Multispot HIV-1/HIV-2. A subset was also tested with 4 other rapid tests and the Architect HIV Antigen/Antibody Combo^®, a fourth generation assay.

 Results:  Of 99,111 specimens screened from April 2006 to March 2008, 60 were NAAT-positive/seronegative by 1 of 3 different immunoassays and 2 were NAAT-positive/Western blot indeterminate. Third-generation testing correctly detected antibody in 34 specimens (55%; 95%CI 42 to 67); Multispot detected antibody in 16 (26%; 95%CI 16 to 38). Of the 62 specimens, 33 (53%) had sufficient quantity for further testing. Third-generation testing correctly detected antibody in 19 of 33 specimens (57%; 95%CI 40 to 73); Clearview Complete in 8 of 27 (30%; 95%CI 15 to 49); Unigold Recombigen HIV in 8 of 33: (24%; 95%CI 12 to 41); Clearview HIV 1/2 Statpak in 7 of 31 (23%; 95%CI 11 to 40); Oraquick Advance Rapid HIV-1/2 in 7 of 32 (22%; 95%CI 10 to 39). The rapid tests correctly detected antibody in 37 to 47% of cases detected by third generation testing. The sensitivity for early HIV infection of the antigen/antibody combo assay was 87% (95%CI 72 to 96).

Conclusions:  Many FDA-approved rapid HIV tests failed to detect half of the early HIV infection cases in whom antibody was present and at least two-thirds of the cases detectable by NAAT. Rapid test sensitivities for early HIV infection ranged from 23 to 31% compared with 55 to 57% for the third generation assay and 87% for the fourth generation assay. Programs that screen high-incidence populations with rapid tests should consider supplemental testing with NAAT. These data support the need for more sensitive antigen-based point-of-care screening tests for early HIV infection.