The Deadliest Catch: Fishing for HIV in New Waters

In the absence of an effective HIV vaccine, case findings and treatments are the mainstay of HIV prevention. Effective treatments are available, but more than 25% of HIV-infected individuals in the United States may not know that they are infected (1). Perhaps as a result, the rate of HIV transmission in the United States seems to be holding steady (2, 3). Two years ago, the Centers for Disease Control and Prevention (CDC) responded by announcing a bold new strategy to curb HIV transmission: screening average-risk individuals in an attempt to bring more people with HIV infection into treatment and care. The new strategy proposed reaching beyond HIV voluntary counseling and testing sites (places where people who believe they are at risk for HIV can get tested) to screen for HIV in other medical settings. Additional key recommendations included simplifying requirements for obtaining written informed consent for HIV testing and increasing the use of rapid HIV tests, which would make it possible to test and deliver a preliminary positive result during a single brief visit. The vision guiding these policy recommendations was to make HIV screening a routine procedure in U.S. primary care clinics, urgent care centers, emergency departments, and hospital wards (2). In this issue, Walensky and colleagues (4) report one emergency department's experience with implementing this type of screening. They show that these new waters can be treacherous. For their study of unselected HIV screening in a Boston, Massachusetts, emergency department, they recruited 849 study participants from a representative sample of adult emergency department patients and used an oral test approved by the U.S. Food and Drug Administration. Thirty-nine (4.6%) patients had a reactive result for HIV antibodies and were offered confirmatory testing; 8 declined and received only this preliminary positive result. Of the 31 patients who agreed to confirmatory testing, only 5 (16%) were HIV infected. The remaining 26 patients with reactive oral tests were not HIV infectedalthough the Western blots for half of these patients had nonspecific HIV-indeterminate banding patterns. The authors concluded that rapid HIV testing linked to confirmatory testing and follow-up was acceptable to clinicians and succeeded in making HIV-positive patients aware of their infection. However, most of the positive results were false positive, which occurred at a higher rate than expected. Therefore, the authors cautioned against the use of oral HIV testing and recommended that for now, physicians and the public temper expectations about the accuracy of HIV screening tests in low-prevalence settings. Should the high rate of false-positive screening results cause us to question the CDC's recommendations about testing in emergency departments and primary care? Yes, and maybe. Like fishermen casting a wide net, clinicians who use sensitive screening tests for rare diseases (such as HIV) should be prepared to haul in many false-positive results to find each true-positive case. Walensky and colleagues (4) note that the public accepts screening tests (such as mammography) that have even lower posttest probabilities of disease. In this context, screening for HIV in primary care offices might make good sense and deserves extended discussion. However, their experience raises concerns about implementing public health screening in acute care settings. Emergency physicians rarely screen for chronic diseases in acutely ill patients. The time, effort, resources, and continuity of physicianpatient relationships that facilitate sorting out true-positive from false-positive results are not available in acute care settings. Therefore, is it even reasonable to consider urgent care centers and emergency departments as new territory for HIV screening? Acute care physicians may be unlikely to embrace a new role in screening for HIV solely for public health reasons. They may respond to another, more compelling case for having rapid HIV testing routinely available in acute care settings: It could improve diagnosis and treatment. First, knowing that a patient is HIV infected can be important to clinical management of many acute clinical problems (for example, headache and fever, pneumonia, or diarrhea). Second, being able to do rapid HIV testing makes it much easier for emergency physicians to manage occupational or nonoccupational exposures that might merit postexposure antiretroviral therapy. Third, and perhaps most important from a prevention perspective, patients go to acute care settings when they develop symptoms of acute HIV infection (5). Acute HIV infection is the most infectious stage of HIV disease and is, consequently, a public health emergency in which sexual and injection partners can be protected from high risk for infection if HIV is promptly diagnosed and patients are counseled. Acute HIV infections may be more prevalent in acute care settings than we thought: 2 previous studies (also conducted in Boston) have found evidence of antibody-negative acute HIV in acutely ill patients with viral symptoms (6, 7). If rapid tests could identify both acute and nonacute HIV infections, this would create a powerful incentive for acute care settings to embrace at least targeted HIV testing. Routine HIV screening in these settings would then be less of a stretch. Before we begin promoting HIV screening in the emergency departmentthat is, encouraging a mass shift in the approach that acute care physicians take to HIVour first task is to ensure that the proposed screening methods are as robust as possible. The unexpected high rate of false-positive results in Walensky and colleagues' study (4) emphasizes that even HIV tests approved by the U.S. Food and Drug Administration may not do well in acute care settings. Emergency department patients without symptoms of HIV infection have a lower pretest probability of infection than high-risk patients and may have conditions (such as autoimmune disorders or liver disease) that predispose to false-positive HIV antibody screening results. Most of the studies reporting clusters of false-positive results (8, 9) used oral antibody tests similar to those used by Walensky and colleagues (4). Using blood samples rather than oral fluid can increase the specificity of antibody screening tests (10). However, the requirement to draw blood might deter patients who are not ill and have no other reason to have blood drawn from agreeing to HIV testing. Physicians in developing countries use more accurate screening algorithms that combine 2 or 3 complementary rapid tests, either in parallel or in series (11). Current rapid HIV tests are antibody based and cannot detect patients with early acute HIV infection. Emerging technologies may play an important role in making acute care HIV screening easier and more effective. Several companies are evaluating a new generation of rapid HIV tests (1214) that directly detect HIV RNA or p24 antigen (rather than HIV antibodies) in patient samples. A rapid HIV antigen or HIV RNA test could perhaps be combined with rapid HIV antibody tests. This combination might detect a case of hyperinfectious acute HIV infectionin which HIV RNA levels are very highthat an antibody test would miss but the new test would detect. Moreover, the rate of false-positive results if 2 tests were reactive would be much lower than that with a single preliminary positive rapid test result. A combination rapid test algorithm capable of screening for both acute and nonacute HIV infection with high accuracy would be an important tool for clinical care and public HIV screening. Of course, false-positive results can occur even with well-designed screening algorithms. Therefore, acute care settings must have standardized confirmatory testing and quality assurance monitoring programs to support the CDC's policy recommendation to do public health screening for HIV (14). Ways to improve rapid HIV test performance are now available, and emerging technologies promise even better tools in the near future. Therefore, it makes sense to continue moving rapid HIV testing into acute care settings. However, a sustainable model for screening in these settings must avoid overburdening emergency departments that are already stretched beyond their limits. Teams with dedicated funding to support and follow up HIV testing would be 1 solution. These teams could provide linkage case management for patients identified in such settingssupporting and monitoring the disclosure of test results to patients, coordinating confirmatory testing, providing HIV risk reduction counseling or partner services, and ensuring linkage of newly identified patients to care. Although it might seem difficult for a small team to provide such services in various sites in a hospital, expecting busy emergency department providers to do the same is unrealistic. As challenging as this new territory may be, the potential yield for innovative programs is great. Until a vaccine becomes available, early detection and treatment continues to be our best hope to stop the spread of HIV. With proper nets; the right tackle; and, most important, a well-supported fleet, fishing for HIV in acute care settings just might be the right strategy.