CDC backs new HIV testing approach — Update your clinical lab practices
Executive Summary
The Centers for Disease Control and Prevention has issued a new approach for HIV testing in laboratories that capitalizes on the latest technology to improve diagnosis of acute infection, the earliest stage of HIV infection when people are most likely to transmit the virus.
• The new approach for HIV testing in laboratories will help avoid missing early infections that go undetected. Using the updated testing recommendations, HIV infection can be diagnosed as much as three to four weeks earlier than with the previous testing approach.
• The HIV-1 Western Blot test is no longer recommended because it is negative during early HIV-1 infections and also misclassifies HIV-2 infections.
Approach banks on latest technology to up acute infection diagnosis
Since the Centers for Disease Control and Prevention (CDC) issued a 2006 recommendation that all Americans ages 13-64 get tested for HIV, the proportion of people who are unaware of their HIV infection has seen a steady decline, from about 20% to 16%. As of 2009, an estimated 83 million adults ages 18-64 reported they had been tested for HIV.1
The CDC has just issued a new approach for HIV testing in laboratories that capitalizes on the latest technology to improve diagnosis of acute infection, the earliest stage of HIV infection when people are most likely to transmit the virus.2
The guidance might help the nation reduce the number of people who are unaware of their HIV status, says Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.(Go to the CDC’s HIV/AIDS Laboratory Tests web site, http://1.usa.gov/1md3gUZ, to download the updated recommendations, as well as Quick Reference: Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens. Both are under "Laboratory Testing Guidance." A step-by-step guide is available by going to http://1.usa.gov/1md48Je.)
"Identifying acute infections has long been one of our nation’s biggest HIV prevention challenges, since these infections eluded traditional testing technologies," said Mermin in a statement accompanying the guidance’s publication. "But with consistent and widespread use of this new testing method, we can diagnose people several weeks earlier than before."
The new approach for HIV testing in laboratories will help avoid missing early infections that go undetected, explains Bernard Branson, MD, a medical epidemiologist in CDC’s Division of HIV/AIDS Prevention. The new recommendations call for a series of tests to first detect the virus before antibodies develop and then correctly distinguish between HIV-1 and HIV-2 to ensure correct treatment, Branson states. This recommendation reflects a major shift away from the HIV-1 Western Blot test, which is no longer recommended because it is negative during early HIV-1 infections and also misclassifies HIV-2 infections.
The new recommendation includes "fourth generation" tests approved by the Food and Drug Administration (FDA) as the initial HIV test, explains Branson. Fourth generation tests detect antibodies to HIV-1 and HIV-2, as well as the HIV-1 p24 antigen that is present before antibodies develop, Branson states.
"Using the updated testing recommendations, HIV infection can be diagnosed as much as three to four weeks earlier than with the previous testing approach," says Branson. "Early diagnosis, particularly in the highly infectious acute phase of HIV infection, is essential for stopping HIV transmission and ensuring that people with HIV receive life-saving treatment and care."
Algorithm offers aid
The CDC and the Association of Public Health Laboratories issued the recommendations based on HIV tests approved by the FDA as of December 2012, as well as scientific evidence, laboratory experience, and expert opinion collected from 2007 through December 2013. The recommendations do not include the rapid HIV-1/HIV-2 antigen/antibody combination test approved by the FDA in August 2013, because evidence of performance in the algorithm was insufficient, or HIV-2 nucleic acid tests (NATs), which lack FDA approval.2
The recommended algorithm has several advantages over previous recommendations, because it offers:
• more accurate laboratory diagnosis of acute HIV-1 infection;
• equally accurate laboratory diagnosis of established HIV-1 infection;
• more accurate laboratory diagnosis of HIV-2 infection;
• fewer indeterminate results;
• faster turnaround time for most test results.2
The CDC and the Association of Public Health Laboratories will continue to monitor the introduction and FDA approval of diagnostic assays for HIV infection, and they will update recommendations when necessary. The two agencies will continue to monitor the performance of the laboratory testing algorithm and review the performance of the recommended algorithm at least every five years.
How does it differ?
How does the new guidance differ from previous recommendations? The previously recommended HIV testing algorithms centered on screening for HIV-1 antibodies.3 Specific testing for HIV-2 antibodies was recommended in limited circumstances.4
The new algorithm screens for HIV-1 and HIV-2 antibodies, and it distinguishes HIV-1 from HIV-2 antibodies using a single supplemental antibody differentiation immunoassay. According to public health officials, this approach is simpler and more accurate than the 1992 guidance, because it no longer depends on laboratory access to clinical, demographic, or behavioral information suggestive of possible HIV-2 exposure.2 Because the new algorithm no longer relies on HIV-1 Western blot or HIV-1 indirect immunofluorescence assay (IFA) as a supplemental test, it returns fewer specimens with indeterminate results that require resolution by a follow-up test conducted several months later.2
Supplemental testing with HIV-1 Western blot or HIV-1 IFA previously had been recommended for all specimens submitted for testing after a reactive rapid HIV test result, even if the initial laboratory immunoassay was nonreactive. Now, specimens submitted after any reactive rapid HIV test result — including the HIV-1/HIV-2 antibody differentiation assay, when it is used as an initial rapid test, and the HIV-1/HIV-2 antigen/antibody combination rapid test — are tested according to the same algorithm as all other specimens. No further supplemental testing is required if the result of the initial antigen/antibody combination immunoassay is nonreactive, the new guidance states.2
Follow the steps
With the new guidance, all testing begins with a "fourth generation" HIV test, which detects HIV in the blood earlier than previously recommended antibody tests.
The fourth generation tests identify the HIV-1 p24 antigen, a viral protein which appears in the blood sooner than antibodies. If the test is negative, no further testing is required.
If the fourth generation test is positive, obtain an immunoassay that differentiates HIV-1 from HIV-2 antibodies. Such a test produces results faster than the previously recommended Western Blot. It also distinguishes between HIV-1 and HIV-2, which the Western Blot cannot. Such a distinction can have important treatment implications for a patient, states the CDC.
If a positive result is reached on the initial immunoassay, but a negative or indeterminate result on the antibody differentiation assay, the recommendations call for proceeding to HIV-1 nucleic acid testing for resolution. Such testing will ensure accurate detection of early infection or indicate a false positive from the fourth generation test.2
Testing is "linchpin"
The CDC is calling for laboratories to adopt the new guidance as quickly as possible. Because it can identify infection several weeks earlier than before, it might give public health officials a jump on pinpointing infection.
HIV testing is the linchpin for prevention and treatment, said Mermin.
"For people who test HIV-positive, diagnosis opens the door to life-saving treatment, which also reduces the risk of transmitting HIV to others," stated Mermin. "For those who test negative, knowing their status empowers them to remain HIV-free."
- Centers for Disease Control and Prevention. Vital signs: HIV testing and diagnosis among adults — United States, 2001-2009. MMWR 2010; 59(47):1550-1555.
- Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. Accessed at http://1.usa.gov/1yVdej7.
- Centers for Disease Control and Prevention. Interpretation and use of the Western blot assay for serodiagnosis of human immunodeficiency virus type 1 infections. MMWR 1989; 38(S-7):1-7.
- O’Brien TR, George JR, Epstein JS, et al. Testing for antibodies to human immunodeficiency virus type 2 in the United States. MMWR Recomm Rep 1992; 41(RR-12):
1-9.
