CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
William Check, PhD
June 2016—Laboratories that use the HIV testing algorithm the CDC recommended in 2014 report shorter turnaround times for those with detectable antibodies. And among state and local public health laboratories that responded to a 2015 survey, more than half report having implemented the algorithm. This was just some of the information presented in March at the annual HIV Diagnostics Conference, where speakers, a handful of whom spoke with CAP TODAY since, shared data on the use and efficacy of the algorithm.
“From a recent Association of Public Health Laboratories survey [reported at the conference] we know that the algorithm has been implemented in approximately 55 percent of state and local public health labs that responded,” says Michele Owen, PhD, conference co-chair and the CDC’s associate director for laboratory science, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. “We also have limited data indicating some labs are using parts of the new algorithm.”
“So far the biggest success associated with implementation of the algorithm,” she says, “is the drastic improvement in result turnaround times for HIV-infected individuals who have detectable antibodies—those who are positive at the second step of the algorithm.”
Dr. Pentella
Michael Pentella, PhD, D(ABMM), director of the Massachusetts State Public Health Laboratory, presented data from the APHL survey. “In 2009, before the [2014 CDC] algorithm was introduced, about 48 of 61 public health laboratories that responded said they were using the Western blot test,” Dr. Pentella tells CAP TODAY. The 2014 algorithm recommended that the Western blot be replaced with an assay that differentiates antibodies to HIV-1 and HIV-2, such as the Bio-Rad Multispot rapid test, which turns positive a week earlier after infection than the Western blot. By 2015, the number of laboratories using the Western blot had dropped to 10 of 74 responding labs that were doing HIV testing at the time of the survey. “We don’t know why those 10 are still doing it,” Dr. Pentella says.
Thomas Alexander, PhD, D(ABMLI), recalls his laboratory having a problem with the initial fourth-generation combination assay in 2010, before the CDC’s algorithm became available. They had a sample that was positive in the combination assay but negative on the confirming assay. “The person exposed turned out to be a low positive,” says Dr. Alexander, who is an immunologist in the special procedures laboratory in the Department of Pathology and Laboratory Medicine Group, Summa Health System, Akron, Ohio. “We had to wait for three tests to find out that it was falsely negative. It was more expensive, it took more time, and the infection control department wasn’t wild about it.”
Dr. Alexander
The newest type of combination test, which differentiates immediately among positivity to HIV-1 and HIV-2 antibody and p24 antigen, can prevent these types of situations, he says. “With antigen-positive, antibody-negative primary infection you only get a single result with [fourth-generation assays]. You have to do an antigen confirmation test. The advantage of the so-called fifth-generation tests is you get a separate result [for antibody and antigen]. You can confirm with that one test.” Dr. Alexander acknowledges that these cases of acute infection are uncommon in his patient population. He estimates that he has had fewer than 10 specimens that required that third level of testing. “It’s very rare that it happens, but it does.”
In practice, it appears that fourth- and fifth-generation combination assays are similarly effective in detecting HIV infection, according to data reported by Teal Clocksin, MS, technical specialist at TriCore Reference Laboratories in Albuquerque, NM. “What’s important for people to understand is that the lab-based HIV combination assays from all three of these manufacturers are quality assays,” Clocksin says of the Abbott, Siemens, and Bio-Rad assays. “The real challenge is getting laboratories to use them.” There are sensitivity differences among them, he adds, “but those differences are minor for our population.”
Additional positive data on the fourth-generation algorithm came from Christopher Pilcher, MD, associate professor of medicine in the HIV/AIDS Division, University of California, San Francisco. In his talk, Dr. Pilcher reported that implementing the algorithm for high-throughput testing every two hours was feasible in a large hospital-based clinical laboratory. He and his colleagues found that the number of infections classified correctly without send-out testing was greater compared with their previous testing procedure.
“The new algorithm is designed to allow quicker and more accurate resolution of infection status and did actually get slightly faster results to patients overall,” he tells CAP TODAY. However, the type of results available in the first day or two led to confusion in certain cases, he says, because the positive predictive value of an initial positive result is low in low-prevalence screening populations. Clinicians and patients need to understand the meaning of these early results.
Laboratory testing for HIV has progressed over three decades from simple tests that detected only antibody against HIV type 1 to combination tests that simultaneously detect antibody to types 1 and 2 as well as p24 antigen, which appears in the blood weeks earlier than antibody. Molecular tests detect HIV nucleic acid, the first viral product to rise in the patient’s blood, within days of initial exposure/infection and a week or so ahead of fourth-generation combination assays.