Combination therapy had controlled Bradley Land's HIV, but it also drained the fat from his face, marking it with the gaunt canyons that belied his clinical good health. The social and psychological effects were devastating, 'I was looking forward to suicide,' the Los Angeles resident said.
Then in 2003, six treatments with an experimental injection ameliorated the worst of his facial wasting and people began to look at him 'as a normal person' rather than as a skeletal specter of death.
His story was just one of several moving testimonials an FDA advisory committee heard at a meeting outside of Washington, D.C., March 25. The panel was considering expedited approval of what is called Sculptra for reconstructive purposes of lipoatrophy associated with HIV infection and treatment.
'Facial lipoatrophy has become the scarlet letter of AIDS,' said veteran San Francisco AIDS doc Marcus Conant. 'It is the thing that is bothering our patients the most ... even doctors wait to start their medication.' Nearly half of all patients experience a degree of facial lipoatrophy within three years of beginning therapy.
Some have stopped therapy because they believe it causes the wasting. But Conant said it is unclear whether the syndrome is due to the disease itself and only becomes obvious over time, to the drugs used in treating HIV, or to a combination of factors.
Conant's experience using Sculptra in a research protocol over the last four months has led him to believe, 'It is safe and effective and my patients would benefit tremendously' from its availability.
Sculptra is an injectable poly-L-lactic acid that has been available outside of the U.S. since 1999 under the trade name New-Fill. It has been used in more than 150,000 patients in 33 countries for cosmetic purposes such as filling wrinkles.
Facial wasting associated with HIV is a much more severe problem and significantly more of the product has to be injected to achieve results. The company that developed it was small and did not have the resources to put into those clinical trials. As a result, most of the trials have been investigator initiated, each slightly different, with a small number of patients. That has made it difficult to evaluate and compare results.
A study of 50 patients in Paris used ultrasound to show a significant increase in total skin thickness in the area treated with New-Fill. Photos also documented real improvement. But perhaps most important was the great satisfaction that most patients had.
Peter Engelhard, a Miami Beach physician specializing in HIV, received training in administering New-Fill in Paris and later organized a compassionate use, 100-patient, open-label trial of the product in Florida. HIV physician Douglas Mest organized a parallel trial for patients in the Los Angeles area. Both found similar patterns of ease of administration, safety, and patient satisfaction as were seen in the European trials.
Dr. Engelhard said about half of his patients require a 'touch up treatment' within a year, though some have gone 2-3 years without additional treatment. He believes patients who need the touch up are continuing to experience fat redistribution as they show continued signs of lipodystrophy in other parts of their body. Many patients who go the longest without needing additional injections have switched HIV regimens and their lipodystrophy has either stopped or reversed.
The FDA panel was concerned by formation of what was described as micro-nodules or irregularities where the injections were made. But the doctors said these formations seldom were visible or even noticed by the patients.
While the FDA panel was frustrated with limitations of the data presented to them, there was little doubt that the product is safe. It unanimously recommended approval of Sculptra, but with several caveats. Among them is a training and certification program for doctors who administer it; trials in women and people of color to make sure the effects are no different (most trial participants have been white males); and longer-term safety data. The FDA is expected to follow their advice and approve Sculptra within the next month or so.
The next hurdle for PWAs who want the benefits of Sculptra is getting insurers to pay for it. That is why the AIDS Treatment Activists Coalition (ATAC) pressed for 'the strongest possible labeling language, indicating the reconstructive/corrective nature' of the product, as most insurers do not pay for cosmetic procedures. The FDA agreed with the stronger labeling.
Whether or not financially hard-pressed state ADAP programs agree to add Sculptra to their formulary is unclear. But given the FDA label indication and the often-severe psychological burdens that can accompany facial lipoatrophy, a strong case for inclusion can be made.
