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GURE 2. Number and percentage of positive and false-positive oral fluid and finger-stick whole-blood rapid human immunodeficiency us (HIV) tests, as confirmed by serum Western blot results – New York City,* December 2005–May 2008
..Although 442 (0.27%) of all 166,058 oral fluid rapid IV tests performed during March 2005-May 2008 were se positive and demand for rapid HIV testing in NYC OHMH STD clinics remains high, test operators and unselors have expressed a lack of confidence in oral fluid pid HIV testing since the abrupt and sustained increase
false-positive test results during November 2007–April 108. During this period, nearly half of reactive oral fluid sts in the STD clinics were false positive. Of 31,122 tients tested during those 6 months, 213 (0.69%) reacle oral fluid tests were false positive (specificity: 99.31%, :low the lower limit of the CI of the manufacturer's ecifications) compared with 231 (0.70%) reactive oral uid tests confirmed positive by Western blot. Conseiently, in late May, because results from rapid tests perrmed on whole-blood specimens were consistently more curate than those from oral fluid tests and because rapid sting of whole-blood specimens required fewer additional sts for confirmation of HIV infection, NYC DOHMH jain discontinued use of oral fluid specimen testing in [D clinics. Finger-stick whole-blood specimen testing was instituted as the initial rapid HIV testing method. Oral iid HIV testing data for May 2008, which became availle only after discontinuation of oral fluid testing in the ID clinics, indicated that the recent increase in false
positive oral fluid tests did not continue in May and the test's specificity with oral fluid specimens (99.89%) was within the Cl of the manufacturer's specifications; however, rapid HIV testing of oral fluid specimens has not resumed. Reported by: ) Cummiskey, MPH, M Mavinkurve, MPH, R PanethPollak, MPH, J Borrelli, MPH, A Kowalski, MPH, Bur of Sexually Transmitted Disease Control, New York City Dept of Health and Mental Hygiene. S Blank, MD, B Branson, MD, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC. Editorial Note: Both the number of patients tested for HIV and the percentage who receive their test results have increased since rapid HIV testing was introduced in the New York City STD clinics in 2004. Nationally, public health laboratories report that rapid tests overall and oral fluid tests specifically account for an increasing proportion of all HIV tests (2), and patients are substantially more likely to receive rapid test results than conventional test results (3). The New York City data in this report underscore the importance of routinely comparing reactive rapid test results with confirmatory Western blot test results as an essential component of quality assurance in HIV testing (4). Several other jurisdictions have noted clusters of falsepositive oral fluid rapid HIV tests since an initial report from Minnesota in 2004 (5–8). Although the causes of these clusters of false-positive tests remain unexplained (6), investigations are under way to determine which specific factors (e.g., test device, site, operator, or oral fluid characteristics of specific patients) might be associated with increased numbers of false-positive test results. Several programs have adopted strategies similar to the one used in New York City and are immediately repeating the rapid test on whole-blood specimens from patients who have reactive oral fluid tests. Other strategies under investigation include repeat testing with a second rapid test from a different manufacturer (9).
The specificity of OraQuick rapid tests performed on oral fluid specimens is lower than that of OraQuick rapid tests performed on whole-blood specimens (5). The test manufacturer's 99.8% specificity estimate with oral fluid is based on a clinical trial of 3,682 participants. In New York City STD clinics, performing approximately 5,000 oral fluid tests per month for 3 years, overall specificity has been 99.73%, but the month-to-month specificity has ranged from 98.88% to 99.98%. Although specificity was lower than the manufacturer's claim during certain months, the test's performance in the New York City clinics was not below the Food and Drug Administration (FDA) minimum threshold of 98% for rapid HIV tests.
Because the prevalence of positive HIV tests has decreased among STD clinic patients concomitant with the increasing number of tests, a slight increase in the percentage of reactive rapid tests that are determined to be false positive (decreased positive predictive value) was expected. However, this change does not account for recurrent clusters of false-positive tests.
The advantages of rapid HIV tests, particularly with oral fluid specimens, include increased availability and acceptability of testing among populations at high risk for HIV infection and increased receipt of test results among those tested (3). The strategy used in New York City, with immediate follow-up using a retest on whole-blood specimens, allowed the STD clinics to continue oral fluid rapid testing while mitigating, somewhat, the adverse effects of false-positive results on both patients and clinic personnel. The strategy also allowed health department staff members to detect the increase in false-positive tests promptly, avert the majority of instances in which patients might have left the clinic with an oral fluid test result only (e.g., with
a false-positive result), and avoid the logistical difficult. inherent with training and maintaining inventory, pro ciency, quality assurance, and external controls for
гар: HIV tests from more than one manufacturer.
CDC continues to encourage the use of rapid HIV tes! because they increase the number of persons who are tested and who receive their test results. Six rapid HIV tests havs been approved by FDA since 2002 (10). The New York City data indicate that repeating a rapid test on fingerstick whole blood after receiving a reactive oral fluid test result allows clinic counselors to provide more accurate textresult information to patients while minimizing the number of finger-stick tests that must be performed. Regardless confirmatory testing is required to confirm both oral fluid and whole-blood reactive rapid HIV tests. Before testing, all patients should be informed that reactive rapid HIV test results are preliminary and require confirmation. In general, testing with blood or serum specimens is more accurate than testing with oral fluid and is preferred when feasible, especially in settings where blood specimer.s already are obtained routinely.
Overall, oral fluid rapid tests have performed well and make HIV testing possible in many venues where performing phlebotomy or finger sticks is impractical for screen.ing. However, users should be aware of the unexplained variability in the rate of false-positive test results. CDC will continue to work with FDA and the manufacturer to investigate the causes and extent of increases in falsepositive oral fluid tests, monitor the performance of oral fluid and other rapid tests to ensure that they continue to perform as expected in testing programs, and investigate other combination test strategies to minimize falsepositive test results.
Acknowledgments The findings in this report are based, in part, on contributions bi S Wright, S Wang, Bur of Sexually Transmitted Disease Control D Hanna, C Ramaswamy, Bur of HIV/AIDS Prevention and Contro New York City Dept of Health and Mental Hygiene; the staff and patients of the New York City Dept of Health and Mental Hygiek STD clinics; and J Schillinger and S Rubin, National Center for HN AIDS, Viral Hepatitis, STD, and TB Prevention, CDC. References
1 1. OraSure Technologies, Inc., OraQuick® Advance Rapid HIV
Antibody Test customer letter and package insert. Available at http
www.orasure.com/uploaded/398.pdf. 2. Association of Public Health Laboratories. Public health laborator
issues in brief: 2006 HIV diagnostics survey. Silver Spring, MD Association of Public Health Laboratories; 2007. Available at krog: www.aphl.org/aphlprograms/infectious/documents/hiv_issue_bric. 2007.pdf.
SUS Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Development of rapid HIV tests. In: Blood Products Advisory Committee Sixty-Sixth Meeting (vol I); June 15, 2000; Silver Spring, Maryland. Available at http://www.fda.gov/ohrms/dockets/ ac/00/transcripts/362011.pdf.
Hutchinson AB, Branson BM, Kim A, Farnham PG. A meta-analysis of the effectiveness of alternative HIV counseling and testing methods to increase knowledge of HIV status. AIDS 2006;20:1597–604. CDC. Quality assurance guidelines for testing using rapid HIV antibody tests waived under the Clinical Laboratory Improvement Amendments of 1988. Atlanta, GA: US Department of Health and Human Services, CDC; 2007. Available at http://www.cdc.gov/hiv/topics/ testing/resources/guidelines/pdf/qa_guidlines.pdf. Delaney KP, Branson BM, Uniyal A, et al. Performance of an oral fluid rapid HIV-1/2 test: experience from four CDC studies. AIDS 2006;20:1655-60. Jafa K, Patel P, MacKellar DA, et al. Investigation of false positive results with an oral fluid rapid HIV-1/2 antibody test. PLoS One 2007;1:1-6. Walensky R, Arbelaez C, Reichmann W, et al. Revisiting expectations from rapid HIV tests and confirmation algorithms in the emergency department (Poster). Presented at 15th Conference on Retroviruses and Opportunistic Infections, February 3–6, 2008, Boston, Massachusetts. Available at http://www.retroconference.org/2008/pdfs/ 534.pdf.
8. CDC. Supplemental testing for confirmation of reactive oral fluid
rapid HIV antibody tests. MMWR 2005;54:1287–8. 9. Knoble T, Delaney K, Menendez O, Dowling T, Facente S. Imple
menting RTA to identify false positives and immediately refer to care. San Francisco, CA 2007. Presented at the HIV Diagnostics Conference, Atlanta, GA; December 5-7, 2007. Available at http://hivtesting
conference.org/powerpoint/4_knoble.pps. 10. CDC. FDA-approved rapid HIV antibody screening tests. Atlanta,
GA: US Department of Health and Human Services, CDC; 2008. Available at http://www.cdc.gov/hiv/topics/testing/rapid/rtcomparison.htm.
FROM THE NATIONAL CENTER FOR HEALTH STATISTICS
Age-Adjusted Death Ratest for the Five Leading Causes of Death —
United States, 2001-2006
Per 100,000 standard population.
* Preliminary 2006 data. During 2001-2006, heart disease and cancer were the leading causes of death in the United States, accounting for nearly half of all deaths each year. During this period, the age-adjusted death rate for heart disease declined 19.5%, from 247.8 per 100,000 standard population to 199.4, and the age-adjusted cancer death rate declined 7.8%, from 196.0 to 180.8. Changes in the other leading causes of death were less pronounced. SOURCE: Heron M, Hoyert DL, Xu J, Scott C, Tejada B. Deaths: preliminary data for 2006. Natl Vital Stat Rep 2008;56(16). Available at http://www.cdc.gov/nchs/data/nvsr/nvsr56/nvsr56_16.pdf.
3LE I. Provisional cases of infrequently reported notifiable diseases (<1,000 cases reported during the preceding year) — United States, ak ending June 14, 2008 (24th Week)*
5-year Current Cum weekly
Total cases reported for previous years week 2008 averaget 2007 2006 2005 2004 2003 States reporting cases during current week (No.)
16 20 nfant
97 85 87 76 th-ther (wound & unspecified)
30 33 cellosis
129 121 120 114 104 CA (1) incroid
23 33 17 30 54 era
75 FL (4) ntheria
80 112 108 astern equine
1 st. Louis
13 12 41
12 73 13 827 578 506 338 321 MD (5), VA (1), GA (1), TN (4), AL (1) Ehrlichia ewingii Inaplasma phagocytophilum
20 17 834 646 786
537 362 indetermined
8 337 231 112 59 44
32 ionserotype b
OK (1) inknown serotype
3 181 179 217 177 227 PA (1), GA (1), CO (1) isen diseases
95 itavirus pulmonary syndrome
32 40 26 24 26 nolytic uremic syndrome, postdiarrheals
200 178 OH (1), VA (1) patitis C viral, acute
OK (2), CA (3) 22 infection, pediatric (age <13 yrs) $$
380 436 504 jenza-associated pediatric mortalitys
N IL (2), WI (1), VA (1), NC (1) eriosis
808 884 896 753 696 NY (1), PA (1) isles***
43 55 66 37 56
TX (1) jerogroup B
4 166 193 156
PA (2), MD (1), CO (1), CA (4) nps
6,584 314 258 231 ID (1), NV (1) 'el influenza A virus infections
8 omyelitis, paralytic
1 ovirus infection, nonparalytics
N N N N tacosis
12 avers total:
NY (1), CO (1) chronic
4 hes, human
10 jella, congenital syndrome
1 RS-CoVS **
8 No reported cases. N: Not notifiable. Cum: Cumulative year-to-date counts. Incidence data for reporting years 2007 and 2008 are provisional, whereas data for 2003, 2004, 2005, and 2006 are finalized. Calculated by summing the incidence counts for the current week, the 2 weeks preceding the current week, and the 2 weeks following the current week, for a total of 5 preceding years. Additional information is available at http://www.cdc.gov/epo/dphsi/phs/files/5yearweeklyaverage.pdf. Not notifiable in all states. Data from states where the condition is not notifiable are excluded from this table, except in 2007 and 2008 for the domestic arboviral diseases and influenza-associated pediatric mortality, and in 2003 for SARS-COV. Reporting exceptions are available at http://www.cdc.gov/epo/dphsi/phs/infdis.htm. Includes both neuroinvasive and nonneuroinvasive. Updated weekly from reports to the Division of Vector-Borne Infectious Diseases, National Center for Zoonotic, VectorBorne, and Enteric Diseases (ArboNET Surveillance). Data for West Nile virus are available in Table II. The names of the reporting categories changed in 2008 as a result of revisions to the case definitions. Cases reported prior to 2008 were reported in the categories: Ehrlichiosis, human monocytic (analogous to E. chaffeensis); Ehrlichiosis, human granulocytic (analogous to Anaplasma phagocytophilum), and Ehrlichiosis, unspecified, or other agent (which included cases unable to be clearly placed in other categories, as well as possible cases of E. ewingii). Data for H. influenzae (all ages, all serotypes) are available in Table II. Updated monthly from reports to the Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. Implementation of HIV reporting influences the number of cases reported. Updates of pediatric HIV data have been temporarily suspended until upgrading of the national HIV/AIDS surveillance data management system is completed. Data for HIV/AIDS, when available, are displayed in Table IV, which appears quarterly. Updated weekly from reports to the Influenza Division, National Center for Immunization and Respiratory Diseases. Eighty-four cases occurring during the 2007-08 influenza season have been reported. No measles cases were reported for the current week. Data for meningococcal disease (all serogroups) are available in Table II. In 2008, Q fever acute and chronic reporting categories were recognized as a result of revisions to the Q fever case definition. Prior to that time, case counts were not differentiated with respect to acute and chronic Q fever cases, No rubella cases were reported for the urrent week. Updated weekly from reports to the Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases.