Pulmonary hypertension and HIV

March 2002     View PDF     En español

Treatment for pulmonary hypertension

Until recently, the only treatment available for PH was a GlaxoSmithKline drug called epoprostenol (Flolan). It offers a mixed bag of benefits and drawbacks. It usually works quite well, reversing most for a considerable period. But it comes at a high price in terms of side effects, quality of life and cost. The drug must be directly delivered into a vein (intravenous infusion, IV) 24 hours per day. This means patients must have a surgically implanted IV (HICKMAN* catheter) and carry a continuous infusion pump for the rest of their lives. Having an IV line carries risks of severe and life-threatening infections, notably sepsis. The drug is not a cure and works only as long as it is continued. It is extremely expensive, ranging from $50,000–$100,000 per year, depending on dosage, plus additional costs for the pump, IV lines, etc. As an “orphan drug” (a drug for a relatively rare disease that affects less than 200,000 people annually), these costs are not unusual.

In the fall of 2001, a new, simpler oral drug, bosentan (Tracleer) was approved by the FDA. Bosentan, a tiny pill taken orally twice daily, works by a different mechanism than epoprostenol. It is made by a Swiss company, Actelion, and distributed in the U.S. by Genentech of northern California. While bosentan doesn’t work in every case and may not be adequate in advanced disease, its greater simplicity and consequently better quality of life make it a godsend for many people with PH. It appears to at least halt disease progression within 30 days in most people and improves oxygen flow in many. Fortunately, the mechanism of action of bosentan is believed to be the most relevant mechanism for HIV-associated PH.

People using certain HIV antivirals, specifically ritonavir, need to exercise caution when using bosentan because of possible drug interactions. These interactions have not yet been tested, but it seems likely that ritonavir may increase the blood levels of bosentan, leading to an increased risk of liver-related side effects. Although studies combining bosentan and epoprostenol have not yet begun, there is interest in pursuing this because of their different mechanisms of action. Combination therapy, in this case, would eliminate the quality of life advantages offered by bosentan, but an oral formulation of epoprostenol is in development.

Project Inform encountered a slightly bumpy road in pursuing access to bosentan for HIV-positive people. Well before the drug was approved, it was available on an expanded access basis to people with PH, employing the regulatory mechanisms fought for and won by AIDS activists in earlier years. But in this case, the expanded access program excluded HIV-positive people, on the grounds that the new drug had not yet been specifically tested in HIV-positive people. HIV-positive people had also been excluded from the studies used to license the drug. There were also concerns about interaction with HIV antivirals.

Project Inform, which has played a fundamental role in creating earlier access programs for drugs, responded with a ferocious burst of activity. Through appearances at an FDA Advisory committee, pressure and support from the FDA, and hastily called meetings with company officials and clinical investigators, the ban on access for HIV-positive people was lifted just ten days after we first became aware of it.

For more information on support resources, or referral to PH research sites, call Project Inform's National HIV/AIDS Treatment Hotline at 1-800-822-7422 or email a question.

* HICKMAN is a registered trademark of C.R. Bard, Inc. and BCR, Inc.

Pulmonary hypertension and HIV

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