Ask Dr. Jeff
Question: What's up with atazanavir, the new once-a-day protease inhibitor? When will it be available?
Answer: Currently there is a limited expanded access program for atazanavir (ATV) for people who have problems with cholesterol and triglyceride elevations from the other currently available protease inhibitors (PIs). This program has been slow in development and as a result has not been available too as many people with access to the drug as had been hoped for. The FDA scheduled a meeting of the Antiretroviral Advisory Committee to review the ATV application for FDA approval. From the FDA comes this notice: "On May 13, 2003, the committee will discuss new drug applications (NDA) 21-567 and 21-568, Reyataz (atazanavir sulfate) capsules and powder for oral use, Bristol-Myers Squibb Co., proposed for the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents."
ATV is a once-a-day PI, dosed at 400 mg a day. The main side effect of the drug is an elevation in bilirubin, due to an effect on enzymes in the liver. This is similar to the effects of Crixivan, but appears to occur to a greater degree. Elevation of bilirubin can cause jaundice, a yellowing of the skin and eyes. One other snag in the development of ATV has been a slight change in the electrical conduction in the heart of some people, which does not appear to cause any significant clinical problems. This effect is observed as a very subtle change on the EKG, the electrical tracing of the heart, in some people receiving ATV. There does not appear to be any elevation in the cholesterol or triglycerides caused by ATV, as is currently experienced by many people on ritonavir-boosted PI regimens. Early in development, ATV looked like it might be a good second-line PI, but it did not perform as well as Kaletra in people with some PI resistance. Encouragingly, the resistant mutation that can develop to ATV may not cause resistance to other PIs, so ATV may well be a very good-first line PI, preserving the other PIs for down the road if resistance to ATV develops. In effect, this would add another generation at the front end of the PI class, rather than the back end.
As noted previously, the FDA has scheduled an Advisory Committee hearing to review the ATV application. It is expected that the drug will get a vote to approve from the committee, although there remain some concerns about the liver and EKG issues. Additionally, there remain some concerns about the potency of this drug. It did not outperform Viracept in a head-to-head trial, as the other newer PIs and Sustiva have done. While it did perform the same as Sustiva in a head-to-head trial, the performance of Sustiva in that trial was not as good as has been seen in other trials. However, despite these concerns, ATV is potentially a very significant step forward in the PI class of drugs due to its daily dosing and lack of elevations of cholesterol and triglycerides. If ATV performs as expected as a first-line PI, with good responses from the other PIs used second line, then it will be a very significant addition to the medicine chest.
Dr. Jeffrey T. Schouten is a former general surgeon who has been living with HIV for over 16 years. He is chair of STEP's Publications Advisory Committee and a primary care provider at Harborview's HIV Clinic in Seattle, Washington.
This article was provided by Seattle Treatment Education Project. It is a part of the publication STEP Perspective.