Rapid HIV screening: missed opportunities for HIV diagnosis and prevention

Abstract

Background: Although rapid HIV tests increase the number of persons who are aware of their HIV status, they may fail to detect early HIV infection.

Objectives: To evaluate the sensitivity for early HIV infection of several rapid tests and third- and fourth-generation assays compared with nucleic acid amplification testing (NAAT).

Study design: Sensitivity for early HIV infection was evaluated using 62 NAAT-positive/WB-negative or indeterminate specimens from the CDC Acute HIV Infection study. 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 four FDA-approved rapid tests and Determine HIV-1 Antigen/Antibody Rapid Test(®) and Architect HIV Antigen/Antibody Combo(®), both fourth-generation tests.

Results: Of 99,111 specimens screened from April 2006 to March 2008, 62 met the definition for early HIV infection (60 NAAT-positive/seronegative and 2 NAAT-positive/Western blot indeterminate). Third-generation testing correctly detected antibody in 34 specimens (55%; 95% confidence interval (CI): 42-67); Multispot detected antibody in 16 (26%; 95% CI: 16-38). Of the 62 specimens, 33 (53%) had sufficient quantity for further testing. Rapid test sensitivities for early HIV infection ranged from 22-33% compared with 55-57% for the third-generation assay and 76-88% for the fourth-generation tests.

Conclusions: Many rapid HIV tests failed to detect half of the early HIV infection cases in whom antibody was present. Programs that screen high-incidence populations with rapid tests should consider supplemental testing with NAAT or other antigen-based tests. These data support the need for more sensitive antigen-based point-of-care screening tests for early HIV infection.

Fig. 1

Window of detection of HIV markers early in HIV infection and window period of different generations of immunoassays (IAs) compared to nucleic acid amplification testing (NAAT) for HIV RNA and Western blot positivity. AHI, acute HIV infection; IA, immunoassay; Ab, antibody; Ag, antigen; NAAT, nucleic acid amplification test. Eclipse period: time after HIV acquisition when HIV RNA may be present in very small quantities but is undetectable. Acute HIV infection: phase of early HIV infection when HIV RNA and p24 antigen are detectable but HIV antibodies are not. Early HIV infection: stage of infection prior to HIV seroconversion or Western blot positivity. Fourth-generation assay: detects p24 antigen and IgM/IgG HIV antibodies; third-generation assay detects IgM/IgG HIV antibodies; second-generation and first-generation assays detect IgG HIV antibodies. *Adapted from Fiebig et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 2003, 17:1871–79 and slide courtesy of S. Kleinman (written permission obtained 03/08/2009).

Fig. 2

Specimen testing algorithm for early HIV infection.