A combination of pooled nucleic acid testing and social marketing improved early diagnosis of HIV infection in men who have sex with men in Vancouver, according to research published this week.
A team led by scientists at the British Columbia Centre for Disease Control estimated that by implementing their strategy at six clinics accessed by gay and bisexual men in Vancouver since 2009 prevented transmission of HIV to as many as 75 people, as patients tended to decrease risky behaviors as soon as they received a positive test result.
According to the study, the researchers were also able to make 25 early HIV diagnoses over three years using pooled nucleic acid testing, or pNAAT, to screen high-risk samples that initially tested negative using third-generation enzyme immunoassay methods — an 11.5 percent increase in diagnostic yield.
The study, published in the current issue of the journal AIDS, relied in part on a $2.5 million grant from the Canadian Institutes for Health Research as part of a broader five-year study of acute HIV infection in gay men. The new study focused on this group because men who have sex with men comprised 63 percent of all new HIV diagnoses in British Columbia in 2012.
While pNAAT has long been used to screen blood donations, in recent years it has been more frequently deployed to detect acute HIV infection among high-risk populations.
Acute HIV is a short-lived but highly infectious stage, occupying a window of time from the moment viral RNA first appears in blood plasma to the detection of antibodies against the virus. Viral loads during this window can be "off scale" while antibodies to the virus are as yet undetectable, Mel Krajden, a clinical investigator at the BCCDC and an author on the study, told PCR Insider. This often results in negative tests by standard immunoassay in a person who is actually infected and at a stage when they are exceptionally infectious to others.
As evidenced in the recent study, as well as in others — such as a 2010 study by scientists from the University of California, San Diego (PCR Insider 6/17/2010) — nucleic acid testing can be used to diagnose HIV in these types of patients.
However, the expense of testing remains a roadblock. Krajden runs 200,000 HIV tests per year in multiple public health labs. The recently published study focused on a subset of 75,000 samples. "The real question is the cost effectiveness," said Krajden, "If cost weren't an issue, you could just do a nucleic acid test on every individual."
A nucleic acid PCR test for HIV can detect as few as 20 copies of viral RNA per mL of sample. Pooling samples that initially test negative and running one large test reduces Krajden's costs to about $10 per patient, about a fifth the cost of individual testing.
However, a competing technology might soon make pNAAT obsolete for HIV testing.
A 2011 mathematical model of cost-effectiveness of early testing, published in PLOS One, noted that at least 10 percent of the 56,000 new cases annually in the US are attributable to people with acute infections. Elisa Long, an expert in healthcare management at UCLA and author of the study, compared pNAAT to fourth-generation immunoassays and found that pNAAT is only cost-effective if administered once a year and only for high-risk populations. Meantime, the study found that fourth-generation tests administered every six months could prevent more infections and ultimately be more economically efficient.
Fourth-generation tests such as Abbott Diagnostics' Architect HIV Ag/Ab Combo Assay detect HIV early by measuring both viral antigen and patient antibodies. They are still protein-based, but can detect infection several days sooner than third-generation ELISA-based tests, which only measure antibodies to the virus.
"I haven't done any newer research on this since that [PLOS One] paper, but I think the general finding that with the availability of newer Ag/Ab ELISA tests, which modestly shorten the window period, then the use of nucleic acid testing will likely diminish because the marginal benefit of NAAT is so small," Long wrote in an email to PCR Insider "However, for blood screening, the use of pooled NAAT will continue to reduce the risk of HIV+ samples that are false negatives."
This is in agreement with Krajden's experience on the ground. "It takes you a few days to do the pooling, then you're still missing out on quick identification," he said. "Whereas if you have a fourth-generation positive and then you do the nucleic acid confirmatory test on that single sample on the same day, then you're narrowing that window."
This means that testing labs and public health departments are faced with a decision about whether to continue PCR-based NAAT procedures or to migrate fully to fourth-generation immunoassays. Krajden's labs currently run their NAAT using the Roche Cobas TaqMan HIV-1 v2 NAAT, but will now be comparing the costs for all three types of test — pooled NAAT and third- and fourth-generation immunoassays — to "distinguish the relative effectiveness … from a technological strategy approach," particularly with respect to detecting acute infection, Krajden said.
In May, Roche unveiled new Cobas nucleic acid testing platforms, and said that it would likely eventually phase out older models, such as the one that Krajden's labs are using. The throughput of these newer platforms will be increased, but it remains to be seen whether they will be more cost-effective for pooled NAAT strategies.
While NAAT was critical to the results of the recently published AIDS study, a marketing campaign was also important. Wayne Robert, executive director of the Health Initiative for Men and a study co-author, explained in a statement that this campaign "introduced the concept of acute HIV and its impact on transmission" to many men who have sex with men in Vancouver.
Krajden agreed, noting that "it's about bringing the technology and the community, together. If you have technology without community engagement, you fail. If you have community engagement and no technology, you fail. So it's about linking those two pieces together in a robust way."