Steven F. Ethridge

Post-marketing surveillance of OraQuick whole blood and oral fluid rapid HIV testing.

Objective:Post-marketing surveillance was conducted to monitor the performance of the OraQuick Advance rapid HIV-1/2 antibody test (OraQuick) on whole blood and oral fluid. Design:Surveillance of routinely collected data on clients tested with OraQuick in 368 testing sites affiliated with 17 state and city health departments between 11 August 2004 and 30 June 2005. Methods:For whole blood and oral fluid, we report the median (range) health department OraQuick specificity and positive predictive value (PPV), and the number of clients with discordant results (e.g. who had a reactive rapid test not confirmed positive by Western blot or indirect immunofluorescence). At one site with lower than expected oral-fluid specificity, we evaluated whether device expiration, manufacturing lot, operator practices, or device-storage or testing-area temperatures were associated with false-positive tests. Results:During the surveillance period, 135 724 whole blood and 26 066 oral fluid rapid tests were conducted. The median health department whole blood OraQuick specificity was 99.98% (range: 99.73–100%) and PPV was 99.24% (range: 66.67–100%); the median oral fluid specificity was 99.89% (range: 99.44–100%) and PPV was 90.00% (range: 50.00–100%). A total of 124 discordant results were reported from 68 (0.05%) whole blood and 56 (0.22%) oral fluid rapid tests. The oral fluid specificity at the site with excess oral fluid false-positive tests was 98.7% (95% confidence interval: 98.18–99.11%). The increase in false-positive tests at that site was not associated with any specific device characteristic, operator procedure or temperature condition. Conclusion:The specificity of OraQuick performed on whole blood and oral fluid during post-marketing surveillance was compatible with the manufacturers claim within the package insert. However, one site experienced lower than expected oral fluid specificity. Sites that observe that the specificity of OraQuick is lower than the range indicated in the package insert should notify the manufacturer and evaluate quality assurance procedures.

Performance of an alternative laboratory-based algorithm for diagnosis of HIV infection utilizing a third generation immunoassay, a rapid HIV-1/HIV-2 differentiation test and a DNA or RNA-based nucleic acid amplification test in persons with established HIV-1 infection and blood donors.

BACKGROUND The HIV-1 Western blot (WB) and immunofluorescence assay used to confirm HIV infections are less sensitive during seroconversion than immunoassays (IAs) used for screening. An alternative diagnostic algorithm has been proposed to detect early HIV-1 infection and differentiate HIV-1 from HIV-2. OBJECTIVES We evaluated the performance of an algorithm with a third generation IA that when reactive was followed by a rapid test (Multispot) that differentiates HIV-1 from HIV-2. Multispot-reactive specimens were considered HIV-infected. Multispot-negative specimens were tested with a nucleic acid amplification test (NAAT) for resolution. STUDY DESIGN WB-positive specimens [serum (n=2202), plasma (n=1109) and peripheral blood mononuclear cells (PBMCs) (n=1065)] were obtained from HIV-infected persons not taking antiretrovirals. HIV-uninfected specimens [plasma (n=1517) and PBMCs (n=1508)] with negative IA and NAAT results were obtained from blood donors. Specimens were tested with third generation IAs (Abbott rDNA, ADVIA Centaur, GS HIV1-2 Plus O, Ortho VITROS) in singlet, Multispot, and NAAT (APTIMA (RNA) and AMPLICOR (DNA)). We calculated algorithm sensitivity and specificity and the proportion of IA-reactive specimens requiring NAAT. RESULTS Algorithm sensitivity was 99.95% with APTIMA and 100% with AMPLICOR. One WB-positive specimen reactive by all IAs and AMPLICOR was negative by Multispot and APTIMA. Algorithm specificity was 100% using APTIMA or AMPLICOR as NAAT. From 0.10% (Abbott) to 2.43% (VITROS) of IA-reactive specimens required NAAT. CONCLUSIONS The proposed algorithm performs with high sensitivity and specificity in specimens from persons with established HIV infection and uninfected blood donors and appears to be a good alternative to the current algorithm.

Time Until Emergence of HIV Test Reactivity Following Infection With HIV-1: Implications for Interpreting Test Results and Retesting After Exposure

Background. Understanding the period of time between an exposure resulting in infection with human immunodeficiency virus (HIV) and when a test can reliably detect the presence of that infection, that is, the test window period, may benefit testing programs and clinicians in counseling patients about when the clinician and the patient can be confident a suspected exposure did not result in HIV infection. Methods. We evaluated the intervals between reactivity of the Aptima HIV-1 RNA test (Aptima) and 20 US Food and Drug Administration-approved HIV immunoassays using 222 longitudinally collected plasma specimens from HIV-1 seroconverters from the United States. Using interval-censored survival and binomial regression approaches a multi-model framework was implemented to estimate the relative emergence of test reactivity, referred to here as an inter-test reactivity interval (ITRI). We then combined ITRI results with simulated data for the eclipse period, the time between exposure and detection of HIV virus by Aptima, to estimate the window period for each test. Results. The estimated ITRIs were shorter with each new class of HIV tests, ranging from 5.9 to 24.8 days. The 99th percentiles of the window period probability distribution ranged from 44 days for laboratory screening tests that detect both antigen and antibody to 65 days for the Western blot test. Conclusions. Our directly comparable estimates of the emergence of reactivity for 20 immunoassays are valuable to testing providers for interpreting negative HIV test results obtained shortly after exposure, and for counseling individuals on when to retest after an exposure.

Comparison of alternative interpretive criteria for the HIV-1 Western blot and results of the Multispot HIV-1/HIV-2 Rapid Test for classifying HIV-1 and HIV-2 infections

BACKGROUND HIV-1 Western blot (WB) may be positive in specimens from persons with HIV-2 infection due to cross-reactive antibodies. HIV-1 and HIV-2 infections may be identified using assays designed to differentiate HIV-1 and HIV-2 antibody reactivity. OBJECTIVES To evaluate the ability of the current CDC WB criteria, alternative more stringent HIV-1 WB criteria (2 env plus one gag or pol band) and the Multispot HIV-1/HIV-2 Rapid Test to accurately differentiate HIV-1 and HIV-2 infections. STUDY DESIGN Two panels were used to determine the ability of each method to properly classify HIV-1 and HIV-2 infections: an HIV-2 panel (n=114) determined to be HIV-2 antibody-positive by both Multispot and by a validated HIV-2 WB, and 2135 HIV-1/HIV-2 immunoassay repeatedly reactive (IA-RR) specimens from the New York State Department of Health Laboratory (NYS). RESULTS By CDC WB criteria, 53 (46.5%) HIV-2 panel specimens were HIV-1 WB positive, 60 (52.6%) were indeterminate, and 1 (0.9%) was negative; the alternative WB criteria re-classified 75.5% of the positives as indeterminate. Among 2135 NYS IA-RR specimens, the alternative WB criteria increased the proportion of indeterminates by 0.8%. Only 6 (0.3%) of the NYS specimens were determined to be HIV-2 infections; all 6 were classified either as HIV-1 positive or indeterminate by both WB criteria, but were classified as HIV-2 (n=4) or HIV-1/2 undifferentiated (n=2) by Multispot. CONCLUSIONS The alternative WB criteria classified most of the HIV-2 specimens that were HIV-1 positive by CDC criteria as indeterminate, but also slightly increased the proportion of HIV-1 specimens classified as indeterminate. The WB indeterminate specimens would require further testing or follow-up to resolve the infection status, whereas Multispot directly distinguished HIV-1 from HIV-2.

HIV Screening Practices and Hospital Characteristics in the U.S., 2009-2010

Objectives. The Centers for Disease Control and Prevention recommends HIV screening in U.S. health-care settings unless providers document a yield of undiagnosed HIV infections of <1 per 1,000 population. However, implementation of this guidance has not been widespread and little is known of the characteristics of hospitals with screening practices in place We assessed how screening practices vary with hospital characteristics. Methods. We used a national hospital survey of HIV testing practices, linked to HIV prevalence for the county, parish, borough, or city where the hospital was located, to assess HIV screening of some or all patients by hospitals. We used multivariate logistic regression analysis to assess the association between screening practices and hospital characteristics that were significantly associated with screening in bivariate analyses. Results. Of 376 hospitals in areas of prevalence ≥0.1%, only 25 (6.6%) reported screening all patients for HIV and 131 (34.8%) reported screening some or all patients Among 638 hospitals included, screening some or all patients was significantly (p<0.05) more common at teaching hospitals, hospitals with higher numbers of annual admissions, and hospitals with a high proportion of Medicaid admissions. In multivariable analysis, screening some or all patients was independently associated with admitting more than 15% of Medicaid patients and receiving resources or reimbursement for screening tests. Conclusion. We found that few hospitals surveyed reported screening some or all patients, and failure to screen is common across all types of hospitals in all regions of the country. Expanded reimbursement for screening may increase compliance with the recommendations.

Costs and outcomes of laboratory diagnostic algorithms for the detection of HIV

BACKGROUND An alternative HIV testing algorithm, designed to improve the detection of acute and early infections and differentiate between HIV-1 and HIV-2 antibodies, has been developed by the Centers for Disease Control and Prevention and the Association of Public Health Laboratories. While it promises greater sensitivity, it also raises concerns about costs. OBJECTIVE We sought to compare the most commonly used algorithm which was developed in 1989, a third-generation (3G) immunoassay (IA) and Western blot confirmatory test, to a newer algorithm. The new algorithm includes either a 3G or a fourth-generation (4G) initial IA, followed by confirmatory testing with a HIV-1/HIV-2 differentiation IA and, if needed, a nucleic acid amplification test (NAT). STUDY DESIGN We conducted an analysis of HIV testing costs from the perspective of the laboratory, and classified costs according to IA testing volume. We developed a decision analytic model, populated with cost data from 17 laboratories and published assay performance data, to compare the cost-effectiveness of the testing algorithms for a cohort of 30,000 specimens with a 1% HIV prevalence and 0.1% acute HIV infection prevalence. RESULTS Costs were lower in high-volume laboratories regardless of testing algorithm. For specimens confirmed positive for HIV antibody, the alternative algorithm (IA, Multispot) was less costly than the current algorithm (IA, WB); however, there was wide variation in reported testing costs. For our cohort, the alternative algorithm initiated with a 3G IA and 4G IA identified 15 and 25 more HIV infections, respectively, than the 1989 algorithm. In medium-volume laboratories, the 1989 algorithm was more costly and less effective than the alternative algorithm with a 3G IA; in high-volume laboratories, the alternative algorithm with 3G IA costs

HIV Screening Practices in U.S. Hospitals, 2009-2010

162 more per infection detected. The alternative algorithm with 4G instead of 3G incurred an additional cost of

Performance of the Aptima HIV-1 RNA Qualitative Assay with 16- and 32-Member Specimen Pools

14,400 and

Evaluation of supplemental testing with the Multispot HIV-1/HIV-2 Rapid Test and APTIMA HIV-1 RNA Qualitative Assay to resolve specimens with indeterminate or negative HIV-1 Western blots

4865 in medium- and high-volume labs, respectively. DISCUSSION HIV testing costs varied with IA testing volumes. The additional cost of 4G over 3G IA might be justified by the additional cases of HIV detected and transmissions averted due to earlier detection. CONCLUSION The alternative HIV testing algorithm compares favorably to the 1989 algorithm in terms of cost and effectiveness.

Evaluation of Pooling Strategies for Acute HIV-1 Infection Screening Using Nucleic Acid Amplification Testing

Objective. A 2004 national survey of hospitals showed that 23.4% of hospitals screened for HIV in at least one department, most frequently in labor and delivery departments. However, less than 2% of these hospitals screened patients in inpatient units, urgent care clinics, or emergency departments. In 2006, the Centers for Disease Control and Prevention (CDC) recommended HIV screening for all individuals 13–64 years of age in health-care settings. We determined the frequency of hospital adoption of these CDC recommendations. Methods. We surveyed hospital infection-control personnel at a randomly selected sample of U.S. general medical and surgical hospitals in 2009–2010. Results. Of the 1,476 hospitals selected for the survey, 754 (51.1%) responded to the survey; of those responding, 703 (93.2%) offered HIV tests for patients at the hospital and 206 (27.3%) screened for HIV in at least one department. Screening was most common in larger hospitals (45.7%), hospitals in large metropolitan areas (50.5%), and teaching hospitals (44.4%); it was least common in public hospitals (19.1%). By department, screening was most common in labor and delivery departments (34.6%) and substance abuse clinics (20.7%); it was least common in emergency departments (11.9%), inpatient units (9.6%), and psychiatry/mental health departments (9.4%). More than half of hospitals were not considering implementing CDCs recommendations within the next 12 months. Conclusions. Since 2004, HIV screening in hospitals increased overall and by department. However, the majority of U.S. hospitals have not adopted the CDC recommendations.