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.

Rapid, Fully Automated Digital Immunoassay for p24 Protein with the Sensitivity of Nucleic Acid Amplification for Detecting Acute HIV Infection

“…In high-income countries, public expectation of maximum blood safety has led to the establishment of NAT for blood bank screening despite its cost, but this is not the case for many European and developing countries (24,25 ). The use of NAT-VL for routine clinical screening has also been explored and concluded to be impractical except in highrisk settings, such as sexually transmitted disease clinics (22,23 ).…”

The HIV Seronegative Window Period: Diagnostic Challenges and Solutions

“…Thus, methods which detect the presence of the virus in the blood (p24 antigen, viral RNA, or pro-viral DNA) have enabled the detection of the infection 7-12 days, respectively, prior to seroconversion. This improved detection has enabled the detection of RNA, prior to seroconversion in 0.3% of 14,005 frequently tested MSM in Seattle STD clinic (represents 20% of all HIV infections detected), (Stekler et al 2009); and in 0.08% of 21,222 STD clinic patients in New York City (represents 9% of all HIV infections detected), (Shepard et al, MMWR in press). Linear regression analysis of the detectable part of the active viremia stage led to an estimation that the "beginning" of the active viremia in the blood was 10 days prior to the virus reaching detectable levels in the blood.…”

Prolonged Second Diagnostic Window for Human Immunodeficiency Virus Type 1 in a Fourth-Generation Immunoassay: Are Alternative Testing Strategies Required?

“…Neither the Oraquick HIV-1 Ab nor Determine HIV 1/2 Ag/Ab Combo (also a fourthgeneration assay) would have assisted in diagnosis during the diagnostic window of the Architect HIV Ag/Ab Combo, and their limited sensitivity for the detection of acute HIV infections has been noted elsewhere (23)(24)(25). Given these factors, we believe that fourth-generation assays are insufficient for identifying some acute infections in high-risk individuals.…”

“…Alternative screening algorithms require reconsideration of the role of nucleic acid and other testing, especially in the context of recent high-risk exposure. The issue has been previously raised (26), with benefits demonstrated in pooled samples (27) or in individual testing in highrisk populations (25). Ideally, the testing structure adopted by a revised algorithm would account for the possibility of delayed seroconversion and rapid viral-load decreases in patients, especially given recent cases of unreported use of antiretroviral therapy in HIV study participants (28).…”