Rapid Fingerstick Testing: A New Era in HIV Diagnostics

Rapid Fingerstick Testing: A New Era in HIV Diagnostics

In November, 2002, the FDA announced approval of the OraQuickRapid HIV-1 Antibody Test, which can detect HIV antibodies in fingerstick whole-blood specimens in as few as 20 minutes. On January 31, 2003, the U.S. Department of Health and Human Services announced greatly expanded access to this assay. To discuss the implications of OraQuick for HIV counseling and testing, prevention efforts, and access to care, ACC spoke with Dr. Bernard Branson (CDC), Dr. Carlos del Rio (Emory University), Ms. Susan Larrabee, (Brigham and Women's Hospital), and Dr. Paul E. Sax (Harvard University).

On November 7, 2002, the FDA announced approval of the OraQuick^® Rapid HIV-1 Antibody Test, which can detect HIV antibodies in fingerstick whole-blood specimens in as few as 20 minutes. On January 31, 2003, the U.S. Department of Health and Human Services announced greatly expanded access to this assay through a Clinical Laboratory Improvement Amendments (CLIA) waiver. To discuss the implications of OraQuick for HIV counseling and testing, prevention efforts, and access to care, ACC Executive Editor Matthew O'Rourke spoke with Dr. Bernard Branson, Chief of the Laboratory Determinants & Diagnostics Section of the Division of HIV/AIDS Prevention at the CDC; Dr. Carlos del Rio, Chief of Medicine at Grady Memorial Hospital in Atlanta and Associate Editor of ACC; Ms. Susan Larrabee, HIV social worker at Brigham and Women's Hospital in Boston; and Dr. Paul E. Sax, Clinical Director of the HIV Program and the Division of Infectious Diseases at Brigham and Women's Hospital, and Research Notes Editor of ACC.

Mr. O'Rourke: How does this new rapid test work? How does it compare with conventional ELISA and the currently available rapid test--SUDS^® (Single Use Diagnostic System)?

Dr. Branson: The FDA has approved OraQuick tests for use with fingerstick whole blood. The test consists of a paddle device and developer vial that you place into a stand. You obtain 5 microliters of blood from a fingerstick with something that looks like a plastic inoculating loop. You mix the specimen into the developer vial, insert the paddle device, and wait for 20 to 60 minutes. It is what's called a "lateral-flow device" and has an internal control, so that if the test is negative, you get a single red stripe at the control location; if HIV antibody is detected, you get one stripe at the control location and one stripe at the test location; and if the test is not performed correctly or there is insufficient specimen, you get no stripes on the device.

According to the package insert, the sensitivity is 99.6%. Most of our studies have shown it to be between 99.8% and 100% sensitive. The package insert quotes a specificity of 100%, which also matches pretty closely with our studies. For instance, in the MIRIAD (Mother Infant Rapid Intervention at Delivery) study, we've had only 1 false-positive out of approximately 2200 pregnant women tested.

In comparison with the SUDS rapid test, there are a few key differences. First, SUDS is a "flow-through device" for use with serum or plasma, so you have to centrifuge the specimen before running the test. Second, SUDS has a number of steps where you have to add reagents to the device, whereas OraQuick requires only a single step. Third, unlike OraQuick, SUDS does not have an internal control. Therefore, labs must run a positive and negative control each time that they run a batch of SUDS tests.

Dr. Sax: How does the specificity of the new test compare with that of SUDS?

Dr. Branson: In our studies and according to the package insert, the specificity of SUDS is 99.6% -- less than that of OraQuick. However, some groups have experienced considerably lower specificity with SUDS in clinical practice. The way you read the SUDS test is to look for any blue shading on the membrane at the bottom, but because there's no comparison band available, some people have a tendency to over-read the test. As a result of these issues in test interpretation, we expect many fewer false-positives with OraQuick in low-prevalence populations.

Dr. Sax: That's a critical difference between these two tests. Because the concern with any screening HIV test is that you'll give a false-positive result to a patient, and this is especially true in low-prevalence settings. We were warned stringently to report a positive SUDS as "inconclusive" or "very preliminary." But what patients hear is "you are HIV-positive," and, as a clinician, you want to do everything possible to minimize your uncertainty.

Dr. del Rio: Interestingly, however, in the study we did here at Grady Memorial in Atlanta, we had more false-positives with ELISA than with SUDS. The problem that we had with SUDS was that it was just not rapid enough. It requires a technician to pay full attention to it during the time that it develops. We found SUDS to be an intermediate-speed test with a lot of technical complexities.

Dr. Sax: Exactly. Right now, our hospital runs ELISAs twice a day, so SUDS wasn't really that much more rapid than conventional testing. And with a positive ELISA, you don't give the results to the patient, whereas with a positive SUDS, that was the idea. We actually piloted SUDS here and found an unacceptably high number of false-positives, probably because of lack of technician experience with the test.

Dr. Branson: Interestingly, in the MIRIAD study, we've had 1 false-positive OraQuick but 4 false-positive ELISAs. But as Dr. del Rio noted, the issue with SUDS is that it requires performance in the lab, and that increases turnaround time. Sending specimens to the lab slows down the process regardless of the test's complexity. In an abstract that was just presented at the 10th Retrovirus Conference in Boston, we showed that if you use OraQuick in a point-of-care setting, the turnaround time is 45 minutes, whereas if you send the specimen to the lab for results, the turnaround time is 3 hours.

Mr. O'Rourke: In what patient populations and clinical settings will the test be most appropriate, and in what populations will it be less appropriate?

Dr. del Rio: OraQuick clearly offers the opportunity to do more testing in general and, especially, in under-served populations, urgent care settings, emergency rooms, and new venues outside of healthcare environment. For example, this assay makes it much easier to consider testing in community centers or at events like Gay Pride. Within the clinical care setting, this test will be very useful when you need a rapid answer: source testing before initiating postexposure prophylaxis, at delivery for women who have not received prenatal care, or in the emergency room. Many ERs, including the one at Grady Memorial, don't do HIV tests, because they cannot ensure that post-test counseling will happen; thus, many opportunities to diagnose unsuspected HIV infection are wasted. Many patients who come to ERs should be offered an HIV test because this may be the only contact they have with a healthcare setting. With OraQuick, the follow-up problem is eliminated.

Dr. Sax: Spending money on getting infected people into care is a more efficient strategy to promote health than simply spending money to expand the number of people who are tested. I think that OraQuick can help here. It has clearly been shown that 30% of HIV-infected people who get tested never return for their results and, thus, don't get into care.

Dr. del Rio: The linkage to care is critical. Far too many people are not getting tested or not returning for the results and are learning quite late that they are infected -- perhaps after having advanced to HIV disease and quite likely after having exposed others. What's the point of testing if people aren't going to get the results, let alone get into care?

Ms. Larrabee: I agree with you about many of the benefits of rapid testing; however, given my experience with pretest counseling, I have concerns about approaches such as setting up vans to test at Gay Pride. It would be very difficult to provide the necessary support in such situations for people who have severe reactions to a positive result. Whether the test takes 3 hours or 35 minutes, you need systems in place to help support people in the process and especially in learning that they are likely HIV-infected. The reaction to a preliminary positive result isn't always going to be "Show me how to get into care." Sometimes it's going to be "Show me the George Washington Bridge."

Dr. Sax: You have to assume that the person you are testing may be positive. Some doctors, especially in low-prevalence settings, do not schedule the 2-week follow-up for a patient they think is at low risk, and they say, "Don't worry. I'll call you if there's a problem." If the ELISA turns out to be positive, that puts the doctor and the patient in a difficult situation. So the OraQuick test will give the patient a lot more information before leaving the testing encounter.

Dr. Branson: We've discovered that most people who get a preliminary positive result return for their confirmation results. In the ER study we did in Chicago, we scheduled the patients with preliminary positive results to get their confirmatory results at an HIV-care site. More than 80% of people came back and got into care without any further follow-up.

In addition, although it is true that many people who hear "preliminary positive" may think "definitely positive" as Dr. Sax suggested, our qualitative studies have shown that many people feel that giving preliminary results is a way of breaking the news gently. Right now, if you are told of a positive test result, there's no doubt. Given the hypothetical choice, some people believe that having the preliminary result, where there's still a chance that it could be wrong, would give them coping time. The issue of counseling people who get a positive result with OraQuick is very important: You want to frame the result as cause for serious concern, but not as a definitive answer. One of the surprising findings in our ER studies was that the need for psychological support of patients in giving out preliminary positive results from rapid tests was not as great as we had feared.

Dr. Sax: It is analogous to the home test, which gives you counseling, your result, and, if positive, encourages you to seek care and have a confirmatory test. As with the ER studies of OraQuick you cite, for people who agree to the home test, a positive result is not associated with an unacceptable rate of psychological stress.

Dr. Branson: We need to keep this kind of self-selection in mind. Even when we expand testing to new venues, many people who are not prepared for the results will choose not to get tested. What settings are not appropriate for this test? The answer may be settings where a large proportion of people are not prepared for a positive result.

Ms. Larrabee: In some environments, most people aren't prepared. I've heard some recommendations that this test could be used at bars and other venues where many people are under the influence of alcohol or drugs and most of these people probably aren't in a state to deal with a positive result.

Dr. del Rio: I believe, however, that we are grossly under-testing people. Part of the problem is that we test less frequently than people think we do. I've been very surprised at how many patients in whom I perform an HIV test say, "I was in the hospital two months ago, and simply assumed I was tested."

Dr. Branson: STD clinics in Houston performed blinded seroprevalence studies and discovered that they were not testing about half of the HIV-infected patients. The researchers formed focus groups with the patients and asked them, "Why aren't you getting tested for HIV?" Universally, the patients responded, "We thought we were." Similarly, the women's intake unit at the Cook County detention center has signs posted that say, "We do not test you for HIV." However, when asked when they last received an HIV test, the most common response was "last time I was here."

Dr. Sax: In terms of the applicability of this test in particular settings, occupational postexposure prophylaxis is one area where it could be very helpful. Knowing the serostatus of the source lets you know whether prophylaxis is warranted, and determining this quickly could prevent a lot of these ultimately unnecessary 24- to 72-hour antiretroviral courses that get initiated. Of course, the delay of waiting for the source's consent remains.

Ms. Larrabee: Although it's unusual, victims of sexual assault sometimes are able to convince their assailant to get HIV tested, and this rapid test would certainly be an improvement for these patients considering nonoccupational PEP.

Dr. Sax: Pregnancy is another setting in which this test will make a difference. We know that antiretroviral therapy initiated at delivery can reduce the risk for transmission significantly. Thus, a rapid test of women who present at delivery without having received prenatal care or whose records are not available is critical in further limiting perinatal transmission. This was one of the main ways in which the SUDS test was used.

Dr. Branson: The difficulty with the SUDS test, however, was that in many low-prevalence settings, clinical use yielded more false- than true-positives.

Ms. Larabee: What happens to pre- and post-test counseling with the OraQuick test? Does the emphasis on speed reduce the time for these interventions?

Dr. Branson: I think that counseling and testing continue to be more a function of the environment than they are of the test.

Dr. del Rio: In our experience with SUDS, 42% of people in a walk-in clinic accepted testing, which is a very good response. Patients did not need comprehensive pre-test counseling. We had a brief discussion with them and gave them a literacy-appropriate pamphlet. Post-test counseling, of course, can't be dealt with so quickly.

Dr. Branson: In the counseling and testing guidelines that the CDC updated in November 2001, a distinction is drawn between providing information and providing counseling. It may be appropriate in some settings, especially where prevalence is low, to just provide information, as Dr. del Rio suggests. In fact, the guidelines suggest that in certain environments it may be appropriate to deliver the information through either a pamphlet or a video.

"Opt-out" testing is another model. After the Houston STD clinics discovered how many HIV cases they were missing, all of the STD clinics in Texas moved to a protocol in which when people consent to treatment, HIV testing is included. This time, the signs say, "We test you for HIV unless you ask us not to."

This change has had two effects. First, many more HIV-infected clinic patients have learned of their positive status. Second, the number of people receiving HIV pre-test counseling has fallen by 50%. We're going to have to wait and see what happens with the OraQuick test, but my best guess is that the "opt-out" protocol may become more routine, especially in low prevalence environments As Dr. Sax suggested, you can't triage for counseling and testing based on identifiable risks. In our ER studies in Atlanta and Chicago, about half of all patients who turned out to be positive did not have any identifiable risks on interview.

Mr. O'Rourke: With standard ELISA wouldn't you have a better opportunity for risk-reduction counseling, especially in HIV-negative patients? Theoretically you see these patients twice -- once for the test, once for the results.

Ms. Larrabee: However, that opportunity only exists if people return for their results. In some settings, the proportion of people who don't return seems closer to 50% than the official CDC estimate of 38%. In addition, a large part of pre-test counseling is currently dedicated to helping patients figure out how to cope with the anxiety of waiting for the result -- if that can be eliminated, all the better. If you can get people to return, however, the opportunity for post-test counseling follow-up is critical. There are a lot of myths out there, such as "if I test negative after having put myself at risk, maybe there's something special about me and I'm immune." Only through repeated follow-up and risk-reduction counseling can you effectively dispel these notions.

Dr. Branson: The CDC did a randomized controlled trial comparing pre- and post-test counseling separated by 2 weeks with ELISA with pre- and post-test counseling separated by less than an hour with a rapid test in 3300 individuals. The researchers then followed the HIV-negative people for a year, looking at behavior and at incident STDs. They found no significant differences between the 2 testing groups. However, 30% of the people who were randomized to ELISA did not return for their results.

In addition, the rapid assay may lead us to test many more people with low to moderate HIV risk profiles -- people who would have less cause for anxiety about the result. For example, most pregnant women are at low risk for HIV, and this is a low-prevalence population overall. I don't think that most pregnant women experience much anxiety around HIV testing or need a lot of explanation. It's simply recommended that all pregnant women get tested for HIV regardless of risk profile.

A critical point here is that we can approach HIV prevention from two different perspectives. First, work with HIV-negative people to prevent them from acquiring HIV. Second, do a better job of identifying HIV-infected people and helping them avoid transmitting the virus to others. In the past, we may have underestimated the importance of this second strategy. In a study by Grant Colfax that looked at preventive vaccine volunteers who received counseling and testing every 6 months, these HIV-negative men still had a high level of risky behavior, even after several counseling sessions. However, in a 1-year follow-up of the participants who seroconverted, risk behavior dropped dramatically after they learned that they were HIV-positive.

Dr. Sax: If you remove the psychosocial component for a minute, and look at the issue just from a medical perspective, the question becomes this: Is there anything wrong with a rapid test that can rule out a very serious disease with a high degree of certainty? The answer has to be no. In addition to HIV, I do a lot of general infectious disease testing, and it would be very helpful to simply include HIV testing as part of an infectious-disease workup for certain patients.

Dr. del Rio: Indeed. As things stand now, I perform a variety of tests in patients and can give them the results of their hepatitis or syphilis tests over the phone, but I must have them return in 2 weeks for their HIV results.

Dr. Sax: In terms of saving time, reducing anxiety, and moving people into care, I'm interested in the combined testing strategies used internationally and alluded to in the CDC materials. It seems possible that different tests could be used in combination to both diagnose and confirm HIV infection rapidly, with a sensitivity and specificity approaching that of Western blot.

Dr. Branson: Combination approaches are reasonable in certain scenarios. The need for such strategies was more pressing when we had the less accurate SUDS test. Many of the tests that were used in the international studies to which you refer also had disparate levels of sensitivity and specificity, so it made sense to use them in combinations. In addition, if you are testing in a setting with 30% prevalence, you need to use two tests to avoid the risk for a false-negative result. In the developing world, it's not practical to have patients return for confirmation. Because we are seeing so few false-positives with OraQuick and because it will be used in lower-prevalence settings in the developed world, the question is whether it is worthwhile to use another rapid test to repeat every one of the positives. Rapid confirmation probably won't make sense in the U.S. until we move completely away from Western blot. Mostly for legal reasons, that seems unlikely at present. However, scientifically and economically, it would make a lot of sense to use accurate, combined strategies in place of confirmatory Western blot. Western blot is expensive, complicated, and sometimes scarce. Thus, we'll continue to evaluate rapid test combinations.

Dr. del Rio: When HIV testing was first developed, its primary purpose was as a screening device for the blood supply rather than as a diagnostic tool. Thus, it needed to provide 100% sensitivity in huge numbers of low-risk populations. Those goals don't necessarily apply in the clinical care setting, and rapid testing allows us to finally distinguish between testing the blood supply and diagnosing patients.

Ms. Larrabee: The prevention strategy that the CDC unveiled a couple of years ago had two major foci: First, increase the proportion of people who know their serostatus; second, get more people who are positive into care. Has there been any forethought about how people who test positive will be pulled into care, especially if this test is used in nonclinical settings?

Dr. Branson: That's the flip side to making testing more commonplace: We must have systems to ensure that people get into care. An estimated 225,000 HIV-infected people in the U.S. are undiagnosed, and it's been our goal to identify them and get them access to treatment. We now have a better tool for the former, so we need to make sure that we have good procedures for the latter.

Ms. Larrabee: Many people tell me that lack of insurance and money keep them from getting tested, because they fear learning that they are infected and being unable to get care. We need to have on-site providers who can help people access whatever resources are available in their state, because otherwise these people will disappear.

Dr. Sax: One way to help move people who test positive into care is to providethem with a registry of HIV-care providers in their area and, especially in nonclinical settings, a list of places where they can get confirmatory testing. It's not a perfect system, but this is how the home-test company operates.

Dr. del Rio: The availability of the OraQuick test does raise the bar for trying to get everybody we can into care. However, the risk that people will wait to get tested until they develop an opportunistic infection is graver than the risk that they will disappear after testing positive.

Dr. Branson: We need to consider what this change in testing is going to mean for HIV-negative people. Under the current testing scenario, in which most people seek testing because they think that they are at risk or because it's been recommend to them, many people don't get their results. Keeping the same scenario, but using rapid testing, a million more people every year are going to be told that they are HIV-negative. If we change the scenario, and expand testing to other venues or make it more routine, that number is going to be much higher still. The importance of detecting positives and making sure that they get into care is obvious, but we need to give people who are negative strategies to stay negative. In Australia, for example, the AIDS Council of New South Wales developed a strategy of "negotiated safety," which they defined as talk-test-test-trust: When you enter a new relationship, you use condoms or abstain from intercourse; you do a first HIV test; then do a second test 3 months later to eliminate the possibility of a window-period infection; then you can negotiate what level of safe sex is acceptable to you and your partner.

Mr. O'Rourke: What does the DHHS announcement of expanded access for OraQuick mean for the availability of this test? What will the cost of the test be?

Dr. Branson: The retail cost of the test is expected to be about $12. With the DHHS announcement, the number of sites cleared to use this test will increase from 38,000 to about 170,000. Only about 38,000 labs are authorized to do moderate- or high-complexity testing under CLIA, whereas about an additional 140,000 labs -- the vast majority being physicians' office labs -- are cleared to do diagnostics under certificates of waiver. In addition, it's relatively easy for a lab to get a certificate of waiver. Thus, a lot of community-based organizations have expressed interest in getting a lab certificate simply to be able to perform this test.

Dr. Sax: Compared with drawing blood, the fingerstick test is obviously a lot easier for the clinician and, one would guess, more acceptable to the patient, but the test was also developed for use with oral fluids (hence the name): When might the test be approved for use in oral fluids?

Dr. Branson: The oral-fluid test is still being looked at, and the preliminary data are promising. However, I'm glad that oral fluid was not the first method approved for this assay, because it will give us a little bit of time to look at expanding testing gradually. Working with fingerstick whole blood still provides some minor barriers to the use of the test. With oral fluids, we might have a really rapid expansion of testing in the U.S., and I don't think that we can predict the impact of such widespread use yet.

Dr. Sax: How does the oral-fluid test compare with the fingerstick whole-blood test and with the current FDA-approved test for oral fluids?

Dr. Branson: The way that the rapid oral-fluid test is performed is identical to that of the fingerstick whole blood test. In parallel studies with the fingerstick test, the oral test showed excellent sensitivity and specificity. The current FDA-approved oral-fluid test uses a collection device. You collect the saliva, you send it off to the lab, they do an ELISA, and if that is positive, then they do a Western blot.

Mr. O'Rourke: What are the implications of rapid tests for HIV care in the developing world?

Dr. Branson: For the most part, rapid testing is the only form of testing that is available in the developing world. These tests' low cost and simplicity -- you don't need refrigeration, you don't need a sophisticated lab, you don't need to get someone to come back for the result -- make it possible to ramp up the access to diagnosis in many countries. The CDC's Global AIDS Program has large procurement contracts just to buy and distribute rapid HIV tests for use in Africa and Asia.

Dr. Sax: One of the ironies is that the technology was developed here, exported for use and development in the developing world, and is only now becoming widely available here in the U.S.

Dr. Branson: People perceived rapid testing as a second-class approach here for a long time because it was believed that there were serious advantages to conventional testing. In addition, there were patent and market issues that slowed its introduction in the U.S.

Dr. del Rio: We tend to stigmatize any intervention that is useful in the developing world. Take directly observed therapy: People think, "That's for developing countries -- we're more sophisticated than that." However, the reality is that some of these developing world strategies may make more sense in general, and definitely make more sense in certain key patient populations and clinical settings that we face all the time.

Mr. O'Rourke: You've all alluded to some of the benefits of this test, but what are some of the major issues in HIV testing and counseling that remain, even with the widespread availability of accurate rapid testing?

Dr. Sax: The stigma associated with HIV remains a major barrier to testing and care. When HIV testing was first developed, not much could be done about a positive result. The stigma has lessened, but some of that old pessimism remains. Now that we have effective therapy, we need to move on.

Dr. del Rio: I strongly agree. The rapid test may actually help reduce the stigma, although it won't eliminate it, by making the mechanics of HIV testing more routine.

Dr. Branson: However, I do think that there is a potential drawback with the rapid test: Its very accessibility could create new opportunities for coercion. You might imagine scenarios in which employers, for instance, could more easily coerce people into getting tested now that some of the legal and practical barriers involved in drawing blood and sending it to a lab are no longer present.

Dr. del Rio: Indeed. The ascendant issue of genetic testing underscores the increasing importance of basic informed consent.

Ms. Larrabee: Among the issues that remain is that some people who are infected are ill-prepared for a positive result. I've encountered people who have developmental disabilities and do not understand the test. There are also people who should wait and focus on other life issues before being tested: people who are seriously affected by a recent loss, people with active mental illness who could benefit from further work with a mental health professional before being tested, and people who are in early sobriety. The rapid test doesn't change the fact that HIV disproportionately affects generally vulnerable populations, nor does it mitigate the struggle of coming to terms with being HIV-infected.

— Bernard M. Branson, MD, Carlos del Rio, MD, Susan Larrabee, MSW, LICSW, and Paul E. Sax, MD

Dr. Branson is Chief, Laboratory Determinants & Diagnostics Section of the Division of HIV/AIDS Prevention at the CDC in Atlanta. Dr. del Rio is Associate Editor of ACC. Ms. Larrabee is an HIV social worker at Brigham and Women's Hospital in Boston. Dr. Sax* is Research Notes Editor of ACC.

*Dr. Sax has received speaker and consulting fees from Abbot labs.

Published in AIDS Clinical Care March 1, 2003

Rapid Fingerstick Testing: A New Era in HIV Diagnostics

FURTHER READING

Search

Article Tools

Share

New to Journal Watch?

Rapid Fingerstick Testing: A New Era in HIV Diagnostics

FURTHER READING

Search

Article Tools

Share

Sign-In

New to Journal Watch?