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HIV Screening With Molecular Test Reduces Incidence, Study Finds

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NEW YORK (GenomeWeb) – An acute HIV testing research program called EarlyTest has reduced incidence of HIV infection over a nearly 10-year period, a new study has shown.

Published last week in Clinical Infectious Diseases, the study traced the viral sequences in patients to demonstrate that finding HIV in the pre-seroconversion window had a cumulative effect of avoiding around 100 infections in a high-incidence community in San Diego.

In the first two to four weeks after HIV infection the virus is much more easily transmitted. Patients have higher viral loads and are unlikely to know they are infected so will not have changed any risky behaviors patterns yet, Sanjay Mehta, first author on the CID study and a researcher at the University of San Diego School of Medicine, told GenomeWeb in an interview.

"There has been a growing body of literature saying that up to 50 percent of new infections are caused by people that are in the acute stages of infection," Mehta said.

Researchers at UCSD, the Veterans Affairs Medical Center and the County Department of Public Health of San Diego devised the EarlyTest program in 2007.

The program performs nucleic acid assays on patients who seek testing at community-based clinics in the San Diego area. As previously reported by GenomeWeb, the EarlyTest protocol involves sending blood samples to the American Red Cross for testing using the Hologic Procleix Ultrio nucleic acid test.

Traditional antibody testing can only pick up host antigens six weeks to three months after the initial infection. So-called fourth-generation tests, such as Abbott Diagnostics' Architect HIV Ag/Ab Combo Assay, detect HIV earlier by measuring both viral antigen and patient antibodies. These can pick out infections as early as 21 days, Mehta said.

But nucleic acid-based testing can detect HIV infection in the seven- to 10-day post-infection window, when viral loads are incredibly high but antibody-based tests would still be negative. For example, in one case study a patient had an HIV RNA level of about 2.5 million copies/mL three weeks after the likely transmission event but his enzyme immunoassay was still negative at that point.

For patients like this in the San Diego cohort, a very early diagnosis may have led to changes in behavior that reduced the spread of the virus.

Mehta and his colleagues demonstrated this was the case in their population by molecular phylodynamics. From the sequences of the HIV and the case histories, they generated likely transmission pairs and estimated the directionality of the transmission within local zip codes.

"We looked to see whether transmission chains were more likely to stop in the area in which we were doing our EarlyTest program versus in other locations," Mehta said.

They found that in the area of high incidence where the EarlyTest program was established, about 100 fewer new HIV diagnoses were observed in the last year of the analysis than would have been expected.

Susan Little, the senior researcher on the San Diego study, told GenomeWeb in an email that the group made the decision to outsource HIV nucleic acid testing (NAT) to the Red Cross because it wanted a highly sensitive assay for qualitative detection of HIV RNA.

"This assay is not widely utilized to the best of my knowledge for acute HIV screening, but the Red Cross has given us a very good price for individual donation NAT," Little said. She confirmed that nucleic acid testing is more sensitive than the fourth-generation combo assays, which did not actually exist in 2007 when the group started its screening program.

Whether or not other high-incidence areas might adopt a similar early testing program could ultimately depend on the costs. A modeling study earlier this year by Little and colleagues noted that the EarlyTest screening algorithm would be cost-effective particularly among at-risk men who have sex with men in areas with an HIV prevalence rate of more than 0.4 percent. That study also determined that the Architect HIV Ag/Ab Combo Assay was an alternative for HIV prevalence rates of greater than 0.6 percent.

Mehta noted that new inexpensive, point-of-care molecular testing technologies are already in the pipeline, and they could potentially be used on a widespread basis.

"The key question here is the cost. None of these have rolled out yet so we don't know what the cost per test is going to be. When you figure that the cost per test of a standard rapid antibody test is around $20, [a POC molecular test] would probably have to be somewhere in that range as well."

In the meantime, Mehta noted that the Architect test is commercially available and being rolled out across the country. "I think particularly in high-incidence areas this should be the screening method of choice, and, if possible, a NAT would be even better."

Blood screening trends

The Red Cross does not offer blood testing as a service, but it does work with outside groups on research projects as was the case with Little's group, Susan Stramer, vice president of scientific affairs in the biomedical services division told GenomeWeb in an interview.

"Generally screening tests are more sensitive than diagnostic tests because we're looking at the population prior to the development of disease," Stramer said, adding, "Our goal is different: we're not trying to diagnose disease in a symptomatic individual, we're trying to prevent transmission with very sensitive tools."

The Red Cross currently uses Hologic's Procelix Ultrio Plus triplex assay to screen blood donations for HIV, as well as hepatitis C and B viruses. The other US Food and Drug Administration-approved triplex test is the cobas TaqScreen MPX test from Roche. The Hologic test uses transcription-mediated amplification, or TMA, to amplify RNA transcript using RNA polymerase, Stramer said, while the Roche test uses real-time RT-PCR for HIV and HCV, and PCR for HBV.

These two tests are approved for pooled testing, which also happens to be a cost-saving method used successfully by other labs to enable acute HIV testing. The Red Cross typically screens blood in small pools, although the EarlyTest protocol used individual testing.

Stramer said all blood donations to the Red Cross currently get the Hologic test, but that the contract is periodically reevaluated based on criteria such as performance characteristics and cost.

"Each company is working on new versions, new instrumentation, and as you know the field is rapidly expanding ... when the contract period is over we evaluate both tests and give them equal ability to be our provider depending on certain characteristics," Stramer said.

Hologic's blood screening revenues declined slightly in the second quarter this year, with a major contract in the year-ago quarter with the Japanese Red Cross accounting for some of the decrease. However, the firm said it continues to see trends towards lower blood utilization worldwide.

In a conference call following release of the firm's earnings, Hologic Chairman, President, and CEO Steve MacMillan said: "We are the market leader, so as the market goes so goes our business, and I think that it is important to say that we continue to feel good about continuing to secure the contracts that we have, and this is more a utilization factor as opposed to loosing contracts to competitors."

Roche meanwhile reported major blood screening tender contracts in Thailand, Germany, the UK, and Spain in a 2015 annual report, and the firm's test for the Zika virus was approved by the FDA under an Investigational New Drug application protocol for use in blood screening earlier this year.