The USHER Trial screened 849 patients in the emergency department with an oral OraQuick HIV test. The estimated prevalence of newly identified HIV infection was 0.6%, which supports continued screening in the emergency department in compliance with the CDC guidelines (1
). During this study, 39 patients (4.6%) had reactive results on rapid oral HIV tests; the estimated specificity of these tests was 96.9% (CI, 95.7% to 98.1%). Depending on assumptions about test sensitivity (33.3% to 100%), the positive likelihood ratio ranged from 8.2 to 32.2. Thus, patients with a reactive oral OraQuick HIV screening test in the emergency department have an 8- to 32-fold increased odds of HIV infection relative to the pretest odds.
The manufacturer reported 99.8% specificity for the OraQuick test (CI, 99.6% to 99.9%) (9
). Our results not only suggest that the specificity of the oral OraQuick test is statistically significantly less than that reported by the manufacturer (9
) but also demonstrate a false-positive rate (3.1%) more than 15 times greater than the anticipated specificity of 0.2% (based on the observed prevalence and the manufacturer's specificity).
Our results are consistent with other published data that have suggested lower-than-expected specificities when the oral test was implemented in real clinical settings. In 2005, high false-positive OraQuick test rates associated with oral sampling were reported in New York City, Los Angeles, and San Francisco; a cause was never found (12
). A CDC study in Minneapolis reported an oral OraQuick test specificity of 99.0% and a positive predictive value of 28.1% (estimated prevalence, 0.4%) (13
). More recently, a study in Washington, DC, found that only 9 of 13 patients with reactive oral OraQuick test results were actually HIV-infected (estimated prevalence, 0.4%) (14
Unfortunately, many studies about routine HIV screening do not report details of confirmation. A PubMed search of studies published in English in 2007 using the keywords “HIV screening” and “emergency department” revealed 7 emergency department–based HIV screening programs in the United States that reported using OraQuick tests (oral or fingerstick). Only 3 of the 7 studies documented whether reactive results occurred in HIV-negative patients (14
). In all studies that commented on OraQuick false positivity, at least 2 cases of false-positive results occurred. There is no standardized way of reporting rates of false positivity, and often the provided data are inadequate to discern whether lack of reporting is due to incomplete confirmation, follow-up, or linkage to care. Our results and those of others highlight a need for standardized reporting that should include, at a minimum, the type of test (and means of specimen collection), the confirmation algorithm, and the rate of false positivity based on the confirmation protocol.
Substantial rates of false positivity and low specificity highlight the need for a quick and reliable method of confirmation. Twenty-six patients with reactive tests who were not HIV-infected (that is, had false-positive results) consented to confirmation procedures. Among them, 13 (50%) had indeterminate confirmatory Western blot results; however, Western blot is the initial method of confirmation suggested by CDC (10
). Taken together in the absence of HIV RNA data, these patients' screening and confirmatory results might mistakenly suggest early HIV infection. We propose the addition of an HIV RNA test, which in combination with Western blot, offered a conclusive confirmation in 96.2% of cases. Although HIV RNA testing is more expensive than Western blot ($120 versus $40 per test) (19
), HIV RNA confirmation is unlikely to place a substantially increased financial burden on a testing program because few samples require confirmation.
Our study has several limitations. First, it represents a relatively small sample from a single institution. The literature, however, suggests that other sites are also encountering increased rates of false-positive results (12
). Second, although our study design allows evaluation of test specificity, it does not allow examination of test sensitivity. Because these tests often have different results when implemented clinically compared with preapproval studies, further studies should be conducted to examine the rate of false-negative results. Third, we did not strictly follow the CDC guidelines, which recommend that patients with a negative or indeterminate Western blot result have repeated testing 4 weeks later. Although the simultaneous results of undetectable HIV RNA testing probably rule out early infection, we cannot exclude the possibility of specimen mix-up. However, samples were handled by usual protocols, which suggests that the likelihood of specimen mix-up is very small. Finally, because confirmation results were available on the medical record, the 8 patients without confirmation of HIV status may have systematically elected not to confirm, introducing verification bias. Our sensitivity analyses indicate that if verification bias exists, it does not substantially change our conclusions.
Our experience shows continued enthusiasm for HIV testing in the Brigham and Women's Hospital emergency department (21
). Results indicate that for every 100 patients tested, 95 leave knowing they are negative, and 5 leave with pending confirmatory studies. One of these 5 patients will have HIV infection; the other 4 generally know they are most likely negative within 24 hours (on the basis of a negative EIA result and a normal CD4 cell count) and are confirmed to be HIV negative when HIV RNA results are returned within 1 week. The real efficacy of screening should be measured in true cases identified—cases that, in the absence of screening, would otherwise remain undetected and untreated. Even at the likelihood ratios and posterior probabilities reported in this study, rapid HIV screening functions better than many other screening tests commonly used in U.S. clinical practice. For example, mammography for breast cancer in women age 50 to 59 years has a positive predictive value of 9% (22
The manner in which providers respond to and support patients with reactive test results—regardless of the frequency at which they occur—is critical to ensure the success of HIV screening programs. It is crucial, for example, that “HIV positive” is not documented in the medical record until appropriate follow-up testing confirms preliminary results of rapid HIV screening. Patients should be notified, as part of the counseling process, that a reactive result in the absence of disease is plausible. Furthermore, providers and patients should be equipped with this information ahead of time so that results can be appropriately managed and discussed.
This study supports the original intent of the HIV screening guidelines: to identify undiagnosed HIV infection. Our findings lead to 2 additional conclusions. First, reactive screening results on the OraQuick test are statistically significantly more likely to occur than the manufacturer suggested in individuals who test negative for HIV. Therefore, greater guidance is required to equip both providers and patients to understand and manage preliminary results most effectively. Also, addition of HIV RNA testing to the confirmation algorithm for rapid HIV screening tests in the United States should be considered.