{"id":9996,"date":"2021-02-15T16:11:30","date_gmt":"2021-02-15T21:11:30","guid":{"rendered":"https:\/\/blogs.nejm.org\/hiv-id-observations\/?p=9996"},"modified":"2021-02-15T17:51:58","modified_gmt":"2021-02-15T22:51:58","slug":"time-to-fix-the-hiv-testing-algorithm-and-heres-how-to-do-it","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/time-to-fix-the-hiv-testing-algorithm-and-heres-how-to-do-it\/2021\/02\/15\/","title":{"rendered":"Time to Fix the HIV Testing Algorithm — and Here’s How to Do It"},"content":{"rendered":"
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Photo by Den Harrson on Unsplash.<\/p><\/div>\n

Remember the revised HIV testing algorithm that debuted in 2014?<\/a> The one that was supposed to solve all our problems?<\/p>\n

First, it included a “highly sensitive” screening test that started with a “4th Generation” combination antibody\/antigen test. This decreased the window period between acquiring HIV and having a positive test, thanks to the antigen. Great!<\/p>\n

(These “generation” analogies sure are common in medicine. Is there a line of inheritance? A royal family? Some black sheep?)<\/p>\n

Second, it retired the HIV Western blot as the confirmation test, and substituted a “differentiation assay”, a test that distinguishes between HIV-1 and HIV-2 antibodies. This test is cheaper, faster, more sensitive, and automated, many advantages over the Western blot — may the latter R.I.P, it served us well for many years.<\/p>\n

Hooray! All problems solved. A highly accurate diagnostic test in ID just got even better.<\/p>\n

Well … not quite. The algorithm improved, but a major<\/em> problem remained — what does it mean when a highly sensitive fourth-generation test comes back positive, but the differentiation antibody assay is negative?<\/p>\n

In graphic form, this:<\/p>\n

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These indeterminate results are so frequent that it motivates by far the most common question we ID doctors receive about HIV testing — and was the subject of one of the most popular pre-pandemic posts ever on this site.<\/a><\/p>\n

The problem is that these results represent two clinical states that are diametrically opposite:<\/p>\n

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  1. Acute HIV<\/strong> — a person who recently acquired HIV, and is still in the “window period” before antibody develops. Remember, the differentiation assay is an antibody test.<\/em> It takes a while to turn positive, typically 2-4 weeks.<\/li>\n
  2. False-positive HIV screen<\/strong> — a person who doesn’t have HIV at all.<\/li>\n<\/ol>\n

    In most clinical settings, the second of these (the false-positives) greatly outnumber the acute HIV cases. But we still have to bring back the patient to rule out acute HIV.<\/p>\n

    Which is a pain, and creates several more “worry days” before there is diagnostic certainty.<\/p>\n

    Ah, but what if you could just do an HIV RNA assay — a viral load — as the confirmatory test? And potentially not have to bring the patient back in at all?<\/p>\n

    Such a strategy is now feasible using one of the HIV viral load assays, the Aptima\u00ae HIV-1 Quant Dx.<\/a> It’s the first quantitative viral load test that is also approved for diagnosis of HIV. Off a serum sample sent for HIV screening, the lab can run a qualitative HIV viral load with this assay, with results as follows:<\/p>\n