Viral Load Approved; Free Test Offered to All in U.S. with HIV

On June 3 the FDA approved the Hoffmann-La Roche Amplicor HIV-1 Monitor(TM) viral load test, the first viral load test officially approved for clinical use in the United States. (The same test has already been marketed in Europe, and in some other countries, for over a year.) And Hoffmann-La Roche announced that it will offer two free baseline tests to everyone with HIV in the U.S. (regardless of finances, and regardless of what treatments they may have used or now be using), but only during a 60-day period starting June 17. Patients or physicians who want more information about this free testing program should call 888/TEST-PCR, a toll-free number.

It is recommended that two tests be used to establish a baseline. Because some illnesses and vaccinations can temporarily stimulate HIV (as much as 300 fold) and produce misleading viral load results, "HIV RNA levels should not be measured within a month of acute illnesses or within a month after influenza and pneumococcus immunizations," according to clinical practice recommendations published this month in NATURE MEDICINE (see "Viral Load: New Recommendations for Clinical Practice," below).

The newly-approved test is based on PCR, one of three different methods for measuring viral load which have been widely used in research. (The other two methods are branched DNA, and NASBA; it is widely agreed that all three measure basically the same thing, although there can be variations in how sensitively the different methods detect a particular patient's viral subtypes. For this reason it is usually better for a patient to stay with one kind of test, not use the different tests interchangeably.)

In the U.S., viral load testing has already been available to physicians for about two years, but there have been disadvantages which appear now to have been overcome. PCR was available through "home-brew" tests (meaning that the laboratory which offered the service had to prepare its own reagents), and there have been questions about the quality control at some labs. In contrast, the approved PCR test is provided to the labs in a kit with the reagents strictly standardized, and now the quality control has been checked by the FDA. Also, viral load using branched-DNA technology has been and is available through Chiron Corporation, which recently applied for official FDA approval (the FDA has not acted on Chiron's application yet). The Chiron tests are reliable, but the version now available to physicians (outside of research) cannot measure viral load counts below 10,000 copies. (The newer second-generation branched-DNA test, used by researchers for about two years, can measure down to about 500 copies, and is basically equivalent to the Roche test just approved. An advantage of the Chiron test is that it has been carefully standardized to accurately measure the different subtypes of HIV found all over the world. Roche told us that its test already accurately measures the subtypes commonly found in the U.S., and that its second-generation test will include others as well.)

Comment

Exactly what indications viral load testing would be approved for -- important for reimbursement, and perhaps even more so for improving the prevailing standard of HIV care -- has been controversial. Everyone agrees that the three major kinds of viral load testing (PCR, branched-DNA, and NASBA) do measure what they claim to measure. Everyone agrees that viral load provides important information about prognosis, that persons with a high viral load are likely to do worse. The Roche test was easily approved for these purposes.

A month ago it looked like this was all the approval this viral load test would get -- which would have given insurance companies, HMOs, and other payers an excuse to reimburse for only two viral load tests (for the baseline) in a patient's lifetime, depriving many patients' doctors of the tools to get the most benefit from protease inhibitors and other new therapies. This almost happened because, for historical reasons, the test was reviewed by the FDA's Blood Products Advisory Committee, and by the Biologics division of the FDA, which are relatively unfamiliar with HIV -- and because Roche did a poor job of presenting its case for approval to that committee.

The controversial issue was whether to also recommend the test for monitoring patients, especially for determining whether an antiviral drug or regimen is having the intended antiviral effect in a particular patient. Everything now known about HIV and antivirals strongly supports this use. But the final evidence -- a body count proving that patients who are randomly assigned to have their physician not use viral load do worse than those randomly assigned to have their physician use it -- is not yet available (such trials are under way now). Activist pressure may have helped in getting the FDA to include a statement on clinical use, although hedged:

"The test has also been used as an aid in assessing viral response to antiretroviral treatment as measured by changes in plasma HIV-1 RNA levels. The clinical significance of changes in HIV RNA measurements has not been fully established although several large studies that will more fully determine the role of comparative HIV RNA measurements in patient management are now in progress. HIV-1 RNA levels as measured by PCR were used as one of the surrogate markers in the accelerated approval process for the protease inhibitor drugs Invirase(TM), Crixivan(R), and Norvir(R), and for the reverse transcriptase inhibitor drug Epivir(TM). The utility of plasma HIV-1 RNA in surrogate endpoint determinations has not been fully established."

THE NEW YORK TIMES covered the approval accurately on June 4, but most other media reporting has been superficial. The reason is clear; much of the background on this story was not conveyed in the FDA and Roche press releases. Even the TIMES noted the concern that Roche and other companies had not applied for approval much earlier than they did -- without mentioning that a major reason for this was the lack of clarity at the FDA (and in the professional community) about what evidence would be required for approval.

What You Can Do Now

We believe that everyone with HIV should get the two tests to establish a baseline; and for 60 days only (starting June 17), persons in the U.S. can get them free. (This is not charity from Roche; probably most physicians who have used viral load have used the Chiron test, and Roche clearly hopes that the free offer will get many of them to switch to its product. Roche is donating the test kits, and certain laboratories are donating their services, also clearly in the hope of future business. Patients or their HMOs, etc. will probably need to pay for the physician's office time and the blood draws.) For more information about this free test offer, call the Roche Amplicor(R) Access Program toll-free hotline, 888/TEST-PCR, between 8:30 a.m. and 5:00 p.m. Eastern time; patients can request an enrollment packet to be sent to their physician.

The same hotline will also help patients obtain reimbursement for the test after the 60-day free program.

Even if one does not plan to get further viral load testing, establishing a baseline is important because it helps with decisions about how aggressive to be with therapy, and it leaves open the option of getting tested later to see if one's viral load has changed.