CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Anne Paxton
September 2017—Three years—including a total eclipse of the sun—have sped by since the Centers for Disease Control and Prevention and the Association of Public Health Laboratories recommended a new HIV diagnostic testing algorithm for laboratories. In 2014, the algorithm was seen as bringing HIV test ordering up to speed with the advances in HIV test technology and increasing the accuracy and reliability of HIV screening and diagnosis. Have laboratories made the adjustment, and is the CDC/APHL algorithm proving workable and worthwhile?
Dr. Philip Peters of the CDC Division of HIV/AIDS Prevention. He and others spoke recently about the 2014 HIV testing algorithm and new challenges.
Philip Peters, MD, believes the answers are yes—although the answers aren’t simple. “Having a robust HIV testing program is really a vital part of HIV prevention,” says Dr. Peters, medical officer of the CDC Division of HIV/AIDS Prevention, in an interview with CAP TODAY. Laboratories are successfully adopting the algorithm, but implementation has been met with challenges. “Sometimes newly approved tests don’t neatly fit into the existing framework or algorithm for HIV testing,” he says.
The CDC/APHL algorithm has won widespread adoption and helped unseat the 1980s-era Western blot as the confirmatory assay of choice, probably for good. But in practice, features and limitations of some of the commercially available tests have made the algorithm somewhat tricky to follow, and as new tests have emerged, they have complicated decision points in the algorithm.
Speaking in a panel on how laboratories are dealing with the CDC algorithm, at the AACC annual meeting in August, Dr. Peters and co-presenters outlined the state of current HIV testing relative to the algorithm and discussed some of the potential complications that new HIV diagnostic tests can create, as well as prospects for continued progress in HIV testing. If the AACC audience is any indicator—periodic online surveys during the presentations allowed laboratorians there to vote on user devices—adoption of the algorithm is proceeding but challenges remain.
In brief, the CDC/APHL laboratory algorithm calls for an initial test by an antigen-antibody combination assay. The antigen-antibody combination assays are the Abbott Architect HIV Ag/Ab Combo, Bio-Rad GS HIV Combo Ag/Ab EIA, Siemens Advia Centaur HIV Ag/Ab Combo, and Bio-Rad BioPlex 2200 HIV Ag-Ab; the Roche Elecsys HIV combi PT Immunoassay (approved by the FDA on June 21) is the most recent addition to the list.
If the antigen-antibody combination test is positive, the next step is an antibody-based differentiation assay that differentiates between HIV-1 and HIV-2. Bio-Rad’s Geenius HIV 1/2 Supplemental Assay or, until recently, Bio-Rad’s Multispot HIV-1/HIV-2 Rapid test have been commonly used. If there’s a discrepancy between the initial screening antigen-antibody test and the supplemental assay, the next step is a nucleic acid test, and the only one currently FDA approved for diagnosis is the Hologic Aptima HIV-1 RNA Qualitative Assay. Positive samples at that stage are considered acute HIV-1 infection.
FDA approvals of diagnostic tests and laboratories’ installed instrumentation have both influenced recent trends in HIV testing. In the first years after the 2014 HIV testing algorithm recommendation was issued, it was something of a challenge to get laboratories to use the antigen-antibody combination assays, says Teal Clocksin, MS, technical specialist for TriCore Reference Laboratories, Albuquerque, NM.
After the BioPlex and Advia assays were approved by the FDA in 2015 to detect HIV-1 antibodies, HIV-2 antibodies, and HIV-1 p24 antigen, Clocksin says, “a big portion of what was before a difficulty was essentially eliminated. Many labs already have the Siemens Centaur, which is one of the instruments offering HIV combination testing. And that really opened the door for lots of additional labs to start combination testing.”
“When you have more tests on the menu than just HIV and you’re doing lots of vitamin D or thyroid testing on your instrument, it would be a big decision to switch up everything in your lab just based on one test,” notes Dr. Peters, who has led several studies on acute HIV infection and HIV transmission. “But now that most of the manufacturers are offering the combo test, it’s becoming a lot easier.” About 90 percent of the AACC panel’s audience who were laboratorians reported using a lab-based antigen-antibody combination immunoassay.
Only about 65 percent of the panel’s audience reported using the second assay the algorithm calls for, a differentiation assay, though many audience members were not from the United States. Dr. Peters does not find this response surprising. “It hasn’t been approved as long, and unlike the multiple antigen-antibody tests available from different manufacturers, there’s only one manufacturer [Bio-Rad] that makes the differentiation assays.”
The third step of the algorithm shifts from immunoassay to nucleic acid testing. Several instrumented NAT assays are approved for monitoring patients’ viral loads, but only the Aptima, not automated, is FDA approved for diagnosis. In asking for audience votes at AACC, “We were interested in knowing, first, if people had access to viral load assays within their lab, and, second, if they were using it only for monitoring or using it for help with diagnoses in the case where they have internally validated the test,” Dr. Peters says.
“But there is a tension between the NAT assays because the Aptima is FDA approved for HIV diagnosis but not widely available in clinical labs, so it would be a send-out test, whereas the viral load assays are present in a lot of clinical labs,” he notes. Among the audience members in the AACC session, about half said they were using their nucleic acid test for both diagnosis and monitoring. “That’s about what I expected, because the lab can get a quicker turnaround time than if they have to send it out. But anecdotally, I heard people in the audience saying it would be great if these viral load assays were also FDA approved for HIV diagnosis so they wouldn’t have to validate these tests for an off-label use.”
The most difficult piece of the algorithm at this point is the nucleic acid test, Clocksin says. “The event where you have a positive combo result and a negative confirmation result happens so rarely that it doesn’t make sense for a lot of labs to bring in the Aptima just for that purpose.” As a high-complexity test under CLIA, “Aptima requires specialized training, and most hospitals or even large institutions don’t have that capacity,” so it tends to be a reference test.
Although other nucleic acid tests exist—including the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 and Abbott RealTime HIV-1—they are likely to continue to be used only for viral load testing to monitor treatment. “They may be just as sensitive for detecting an acute infection, but manufacturers don’t have a large incentive to get an additional diagnostic intended use designation from the FDA because it’s such a rare event,” Clocksin says. Single-use nucleic acid tests available only outside the U.S. include the Cepheid GeneXpert, Alere q point-of-care analyzer, and SAMBA (simple amplification-based assay) system. The Roche Cobas Liat Analyzer is a single-use nucleic acid test now in the pipeline for FDA approval.