CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
William Check, PhD
December 2013—Screening to detect HIV infection is poised to make a leap into the 21st century. In his presentations on the proposed new screening algorithm, Bernard M. Branson, MD, points out that in 1989, when the now outmoded algorithm was recommended, the telephone booth was a common sight and the “portable” computer was the size of a small suitcase. Dr. Branson, associate director for laboratory diagnostics in the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention, also points out that 1989 was the year of the dismantling of the Berlin Wall and the Tiananmen Square massacre.
“It is clear that we need an updated algorithm,” Dr. Branson told CAP TODAY. One major problem with the old algorithm is that the sensitivity of the third- and fourth-generation enzyme immunoassays for HIV that are now available surpasses the performance of the confirmatory Western blot. Some contemporary EIAs turn positive as many as 25 days before the Western blot, so the latter may fail to confirm specimens with true infection.
Dr. Branson
“There has been increasing recognition that EIAs currently in use by laboratories all detect HIV infection earlier than the Western blot is able to confirm,” Dr. Branson says. “And there is preliminary evidence that some people repeatedly reactive on these newer assays have negative and indeterminate Western blots. As a result, laboratories may interpret specimens as negative, even though those people have viral RNA that can be detected on molecular assays.”
Another important reason to alter the screening algorithm is to be able to detect HIV infection in the acute stage, the first three months, when the patient has high levels of circulating virus and is highly infectious, yet has no circulating antibody and no specific symptoms. Current treatment guidelines recommend starting therapy as early as possible after infection, and starting in the acute stage would be optimal.
Nathan A. Ledeboer, PhD, D(AB-MM), agrees that “The [proposed] new algorithm recognizes the development of improved immunoassay technology and the importance of discriminating between HIV-1 and HIV-2, as well as the early diagnosis that nucleic acid tests can provide.” Differentiating HIV-1 from HIV-2 is important because drugs used to treat HIV-1 are not effective against HIV-2. Earlier diagnosis means earlier treatment.
Dr. Ledeboer
“The most recent data coming out of management of HIV patients suggests that getting them on highly active antiretroviral therapy as early as possible in the course of their disease will significantly reduce their chances of developing a later AIDS-associated or AIDS-defining illness,” says Dr. Ledeboer, associate professor of pathology at the Medical College of Wisconsin and medical director of clinical microbiology and molecular diagnostics in the Dynacare Laboratories and Froedtert Hospital. He and colleagues are converting now from the 1989 algorithm to the new proposed algorithm. “We want to change to a fourth-generation EIA. The holdup is that only two vendors have FDA clearance and we need to get a new instrument.”
In addition to adopting the new algorithm, Froedtert Hospital exemplifies another important trend: doing HIV screening in places other than publicly funded sites, consistent with the CDC’s 2006 recommendation calling for HIV screening in health care settings generally (Branson BM, et al. MMWR. 2006;55[RR14]:1–17). “Where we encounter HIV patients has changed,” Dr. Ledeboer says. “Many present about once a year and don’t get care in traditional settings, such as a physician’s office. Instead they go to the emergency department or to walk-in or urgent care clinics. If we don’t offer testing where we encounter patients, we will be ineffective in detecting these infections.”
According to Dr. Branson, reimbursement should not be an issue. “Things are changing with the Affordable Care Act,” he says. And this past summer the U.S. Preventive Services Task Force gave HIV screening a grade A recommendation, making screening for 13- to 65-years-olds reimbursable by insurers with no copay.
A study done by the New York City Health and Hospitals Corp. and reported in early November demonstrates the impact of screening programs in such settings. In 2005 the NYC HHC began offering routine HIV testing throughout the care sites of its 11 acute-care hospitals and six large-scale community clinics. From 2005 to 2012, the proportion of age-eligible patients screened doubled, from 9.4 percent to 18 percent, and the rate of concurrent HIV/AIDS diagnosis for newly diagnosed patients dropped from 32.3 percent to 25.3 percent. Data from these sites showed that when more than 20 percent of patients are screened, the yield of new HIV diagnoses levels off at about 0.3 percent. Moreover, trend analysis suggests that concurrent HIV/AIDS diagnosis can be avoided when 40 percent of patients are screened annually, says Eunice Casey, assistant director of HIV services at the NYC HHC.
The CDC and Association of Public Health Laboratories proposed a new algorithm in 2010 “based on theoretical considerations,” Dr. Branson says (Branson BM. J Acquir Immune Defic Syndr. 2010;55 Suppl 2:S102–105). Initial screening is performed with a fourth-generation HIV-1/2 EIA. Positive samples go to an HIV-1/HIV-2 antibody differentiation assay. Detection of antibody to either strain leads to a positive diagnosis. Samples that are HIV-1 negative or indeterminate and HIV-2 negative on the differentiation assay are tested with a nucleic acid test. Positive samples are diagnosed as acute HIV-1 infection; negative samples are declared HIV-1 negative. (See page 42.)
The algorithm was initially evaluated clinically with third-generation assays, since the first fourth-generation assay was not approved until June 2010. Third-generation EIAs detect both IgG and IgM antibody; fourth-generation assays detect p24 antigen as well. Third-generation assays turn positive about 22 days after infection, fourth-generation assays at around 17 days; this represents 15 and 20 days before Western blot, respectively (Masciotra S, et al. J Clin Virol. 2011;52 Suppl 1:S17–22). RNA assays turn positive at about 10 days after infection, 27 days before Western blot.