Speed Test

An antigen and antibody combo assay zeroes in on acute infection

Treatment Horizons by Chael Needle

The diagnosis of acute HIV infection, when the virus is most infectious, has been targeted by physicians and policymakers as key in providing optimal treatment—and to stepping up prevention.

Responding to the success of HPTN 052, a study that found that immediate use of antiretroviral therapy among infected partners in serodiscordant couples helped to dramatically reduce transmission of the virus to the uninfected partner, Michel Sidibé, executive director of UNAIDS, said, “This breakthrough is a serious game changer and will drive the prevention revolution forward. It makes HIV treatment a new priority prevention option. Now we need to make sure that couples have the option to choose Treatment for Prevention and have access to it.”

Detecting HIV during acute infection—the first two to three months, from exposure to the first immune responses—has been difficult in diagnostic settings because established preliminary tests, and many confirmatory tests, depend on the presence of antibodies. Antibodies take time to develop—anywhere from two to twelve weeks. By then, an individual who is infected is well into the stage of acute infection. A viral load test could be used for early detection but it is not commonly used in routine screenings because it is costly and not FDA-cleared for initial diagnosis. Early detection, then, needs a different type of preliminary test.

One such test is the ARCHITECT HIV Ag/Ab Combo Assay, a fourth-generation test introduced by Abbott Laboratories last year and the first to be approved by the FDA. Along with HIV-1 and HIV-2 antibodies, the assay detects the HIV p24 antigen, the foreign protein that most commonly triggers the body’s capability to produce an immune response. As antigens can appear before antibodies, the test can deliver a result days earlier than an antibody-only test and its HIV-related specificity rules out the false positives sometimes produced by antibody-only tests. The combo assay is approved for use in adults, including women who are pregnant, as well as children who are two years-old and up.

The Ag/Ab combo assay has been shown to be more sensitive than antibody tests alone. CDC studies have shown that 10.5 percent of HIV infections in some high-risk populations are missed by antibody-only tests. A 2009 study, published in the Journal of Microbiology, found that the assay detected more than eighty-five percent of early HIV cases missed by other tests.

Additionally, a study presented in May at the annual meeting of the Clinical Virology Symposium in Daytona found the combo assay capable of finding more cases of HIV than older tests. Dr. Daniel Amsterdam, who co-authored this study, helped institute the combo assay at Erie Country Medical Center (ECMC), in Buffalo, New York, where he works. “We selected this test because we felt it had a timeline that was pretty fast, [with results available] within sixty minutes, and it had early detection time associated with it,” says Dr. Amsterdam, who is also Professor of Microbiology & Immunology, Medicine and Pathology, University at Buffalo, which is linked to ECMC.

Not all primary-care settings or labs will have the assay, however. “Doing a test in an organization is not like stocking a supermarket with a particular product,” explains Dr. Amsterdam, adding that an organization will not usually offer more than one test. “A lot of preparation goes on before you can use any test, even an FDA-cleared test, because the laboratory or organization has to go through many steps to validate that test in-house…and I think the organization or the laboratory will use what they have in place. To put this test in place for us was a team effort, including our HIV counselors, information technology people, our emergency department director, our laboratory and infectious disease [unit]. It was a combination of a lot of different hands that were involved in going the way we did.” Also, no state funding is available for assay screening. “For the programs we’ve initiated, we just have to incur those costs.”

Though a May 2011 New England Journal of Medicine article cites global infectious disease experts as looking to the promise of new, more sensitive tests as helping to bring infected individuals into treatment faster and increase prevention efforts, early detection arguably depends on individuals being proactive about getting tested for HIV. “Of the people who are infected in the United States, twenty-one percent are unaware of their status and [those individuals] cause about fifty percent of the new HIV infections,” says Dr. Amsterdam.

“But how do you reach those people to be tested? The passive way is the recently passed New York State law, which says if you are coming to the hospital, to the emergency room, for any reason, even for a hangnail you’re asked if you want to be tested for HIV,” says Dr. Amsterdam, noting that the law covers patients ages thirteen to sixty-four.

“[Screening] gets quite complicated—because people are involved and people are always complicated,” he says, mentioning the reluctance of some patients to want to know their serostatus, or even come in for primary care.

Perhaps one way this law has simplified things is to move beyond referring only those who have been categorized as “at risk” for HIV screening. Says Dr. Amsterdam: “I think that now any sexual encounter is considered potentially risky. So we don’t have to categorize the ‘risky’ sex; it’s ‘sexual encounter.’”

Chael Needle wrote about the HPTN 052 study in the June issue of A&U.

July 2011