The Food and Drug Administration today approved a new test to predict the risk of HIV disease progression in patients by measuring virus levels in blood.
The test is the first HIV-1 test approved using polymerase chain reaction (PCR) technology. By amplifying genetic material from HIV-1, the virus that causes most U.S. AIDS cases, the test can measure the amount of virus in the blood more precisely than other approved technologies.
The newly approved PCR test is not labeled for use as a screening test for HIV or as a diagnostic test to confirm HIV infection.
The new test will be called the Amplicor HIV-1 Monitor Test and will be manufactured and distributed by Roche Diagnostic Systems Inc., Branchburg, N.J., a subsidiary of Roche Molecular Systems Inc. The agency approved it in less than seven months after the application was submitted.
This test works by making a copy of the HIV-1 genetic material and replicating it into millions of copies. The amplified genetic material is tagged with colored indicators so that it can be measured precisely.
FDA's approval of this test for prognosis of HIV-infected patients was based on data from laboratory studies demonstrating that the test is capable of measuring HIV genetic material in the blood and data from clinical studies demonstrating that higher virus levels can be correlated with increased risk of disease progression.
The PCR test's ability to predict the risk of disease progression in HIV infected patients was evaluated in two small clinical studies. These studies looked at patients with advanced HIV disease who had either no previous treatment with antiviral therapies or who had been receiving the drug ZDV (formerly known as AZT) in combination with other antiviral treatments for less than 16 weeks. In these patients, if viral levels, as measured by the PCR test, were high before treatment, or if they increased five-fold between baseline measurements and week eight of therapy, these viral level measures had significant prognostic value related to disease progression. Disease progression was defined as progression to AIDS, an AIDS-related infection, or death.
Laboratory studies demonstrated that the Amplicor HIV-1 Monitor test could sometimes detect and quantify fewer than 400 copies of HIV genetic material (RNA) in a blood sample and that 800 or more copies of HIV RNA were detected 100 percent of the time. Laboratory tests also indicated that the PCR test was specific for HIV-1 -- that is, other unrelated viruses or organisms did not cause a false positive result. In addition, in an analysis of 495 samples from known HIV-1 negative blood donors, none was falsely positive.
The use of the PCR test to measure the effects of antiretroviral therapy was evaluated in two additional clinical studies of antiviral treatments including the protease inhibitor Saquinavir in combination with other drugs, such as ddC or ZDV. In both studies, patients had been previously treated with ZDV. The studies showed decreased levels of viral RNA in patients who received combination therapies, These studies did not, however, show if changes in viral RNA levels are related to clinical responses to drug therapy.
On March 21, FDA's Blood Products Advisory Committee discussed the data presented at the meeting and supported the approval of the test for prognosis of HIV-infected patients. However, the committee also concluded that more studies were needed to determine how physicians should use the test in clinical practice for monitoring therapy. These additional studies, now underway, were required by FDA as a condition of approval.