2003 was a year of abundance -- as far as new HIV drug approvals go. Five new drugs entered the marketplace -- making a total of 21 approved antiretrovirals in the U.S. -- and a consensus is forming about which among the bewildering number of potential combinations are safe and reliable -- and which should be avoided. Yet despite the best of care with all of our medicines and strategies, people continued to fall to AIDS last year -- including several good friends of this publication. Meanwhile, around the world, the first fledgling steps were taken to place just a few of these drugs into the hands of millions of people with HIV who do not know abundance. The magnitude of this effort will transform whole societies, hopefully including our own here in the States. Although there is no cure and still no vaccine, our increasing knowledge about the virus and our bodies justifies hope: that, as long as the will to vanquish AIDS remains strong, living with HIV will one day be easier than it is today.
But is that will durable?
Perhaps it's inevitable that after a year of abundance some bad news would turn up. At the end of 2003 two events sent signals that there might be stumbling blocks on the road to a new era of trouble-free treatments. First, in early December, Abbott Laboratories, the makers of Kaletra, announced that they were dramatically raising the price of their other HIV drug, Norvir. Then Roche and Trimeris announced that further development of T-1249, the successor to their fusion inhibitor, Fuzeon, was being curtailed. These events come in the context of continued shortfalls in government support for AIDS services and treatment programs, ever rising drug costs and insurance premiums, and a faltering political will to pay for just and equitable health care. In response to fears of a coming era of scarcity -- of services, care and research -- a slumbering AIDS activist movement has awakened and begun to lobby Congress and the drug companies from the frontlines of the fight against HIV. Enabled by the Internet, local groups from around the country are increasingly speaking out on a national level to provide ideas, energy and leadership in an unprecedented groundswell of activity.
Norvir had never been very successful on its own as a therapy, and most people who took it as a liquid in the early days still remember its foul taste. But Norvir (ritonavir) had an interesting side effect that gave it a new life: it was unsurpassed at increasing the blood levels of certain other drugs, and only a tiny amount was necessary to do the job. In fact Abbott's follow-up to Norvir, the protease inhibitor lopinavir, depends on ritonavir to give it a boost in the bloodstream -- the combination of the two is called Kaletra. But Norvir could boost drugs from other manufacturers as well, including two of 2003's new protease inhibitors (PIs), Reyataz, from Bristol-Myers Squibb and Lexiva, from GlaxoSmithKline, and it has given new life to some drugs from the first wave of PIs, such as saquinavir and indinavir.
Someone at Abbott no doubt looked at this situation and noted that they were selling a drug for pennies a day that enabled all of these competitors to make gains in the marketplace at their expense. Particularly threatening to Abbott must have been the arrival of Reyataz, a drug that, when boosted, is as potent as Kaletra, without any of the tendency to raise blood lipids to worrisome levels. So Norvir got its own boost: from $4.28 a day to $21.44 for a typical add-on dose, priced, in the words of the company, "to reflect its value."
This 400 percent increase sent a shock wave through the HIV treatment community and almost immediately stimulated a surge of activism at local, national and international levels. Activists first confronted Abbott community reps at the NATAF conference of treatment advocates in Phoenix. In the days that followed, doctors in England (not even affected by the price change) started calling for a boycott of Abbott products and speaking fees. Doctors in the U.S. pledged to turn away Abbott salespeople. The Desert AIDS Project in Palm Springs was the first local AIDS organization to issue a statement denouncing the move. The increasingly vocal HIV professional organizations, HIV Medical Association (HIVMA) and American Academy of HIV Medicine (AAHIVM), each issued strong letters of criticism. The national AIDS Treatment Activists Coalition (ATAC) began circulating press releases and building media interest. Reports in the Wall St. Journal, Washington Post and Seattle Times followed. As the new year begins the groundswell of anti-Abbott activity does not seem to be abating.
While the price increase may pose no immediate threat to already cash-strapped state AIDS Drug Assistance (ADAP) programs or to Medicaid, which have locked-in prices for Norvir that should hold until 2005, ADAP program directors and watchdogs are concerned that a 400 percent price increase by one company will signal open season on pricing for the rest of the industry. With government AIDS funding falling far short of current, not to mention anticipated needs, the carefully constructed safety net systems for vulnerable people who need HIV therapy is in danger of failing. The past year has seen a resurgence of grassroots activism working on these issues, both on the state and national levels, with the SAVE ADAP Committee of ATAC leading the way. In an election year, this effort is set to scale up to a new level of intensity, with individuals from states that have already put people on wait lists for treatment heading to Congress to tell their stories. Some of the first groups to sign on to the lobby effort have been the AIDS Alliance of Northwest Georgia, the Eastern Triad HIV Consortium of North Carolina and Tennessee AIDS Support Services. In response to these challenges, it is encouraging that the grassroots seem to be coming alive, putting a much needed renaissance of AIDS activism into motion.
Abbott's reaction to the protest has been as clumsy as the price hike. Thomas Gegeny, executive director of Houston-based The Center for AIDS, which had publicly criticized Abbott, reported to an email discussion list that an HIV community representative from the company contacted him and suggested they needed to "discuss" their relationship, implying that future financial support from Abbott for the Center's educational projects was in jeopardy. Unrestricted educational grants from pharmaceutical companies are commonly given to local AIDS organizations to fund treatment education and adherence counseling. They are called unrestricted because the companies have no direct control over the content or the materials used in the programs. Gegeny said he later received a visit from another Abbott representative who told him "the only people who seem to have a problem with the price increase were 'gay, white, long-time survivors' and the doctors who treat them -- not the minority-based groups."
AIDS activist Jen Curry recognized this as a crude form of damage control: "This is a classic divide and conquer tactic. The comment manages to insult everyone -- somehow placing elitism and classism at the feet of people with AIDS, rather than on Abbott itself. It renders invisible all the women and people of color who are furious at Abbott."
The Center for AIDS has issued an open letter stating it "will not accept funding from Abbott for any of our community educational forums, publications, etc., on account of the irresponsible and unwarranted increase in the price of Norvir."
The Abbott price hike also sends a chilling message to the sponsors of experimental drugs in the pipeline. For example, tipranavir, from Boehringer Ingelheim, is a protease inhibitor that will depend on Norvir to achieve proper blood levels. Thousands of people are in need of tipranavir's ability to suppress HIV that has become resistant to the approved PIs. The new Norvir price threatens to put the price of a tipranavir regimen in a range to rival the most expensive AIDS drug yet, Fuzeon, from Roche/Trimeris, which also entered the market last year at a price of over $20,000 a year. Abbott's move also came just before the FDA approved an application by Roche for ritonavir-boosted Invirase. A new 500 mg formulation of Invirase soon to be released promised to resurrect this overlooked first generation PI. Now, with the Norvir price hike, the price of this interesting combination will effectively double.
There is much concern that new, needed drugs that can combat resistant virus or that are safer than Kaletra, will be abandoned, due to their dependence on Norvir. Why take a risk of entering the market when Abbott can destroy your product with a new price jump?
Some have drawn a parallel between this situation and the case of anti-competitive behavior that was brought against Microsoft over its bundling of a web browser within its Windows product. Already letters have been sent to several states' attorneys general asking them to look into Abbott's behavior. Indeed, Abbott is currently the subject of lawsuits by the federal and several state governments involving price fixing. Attorney General Ben Chandler of Kentucky is pursuing an action claiming that Abbott manipulated the Average Wholesale Price (AWP) to squeeze higher prices out of Medicaid and Medicare by "knowingly, willfully and intentionally (providing) false and inflated AWP and other pricing information" for their drugs. According to Associated Press, "Chandler said his prosecutors believe pharmaceutical companies have been setting the price 'just wherever they want to set it.' He said consumers feel the effect through the loss of tax dollars and, in the case of Medicare recipients, through excessive prescription co-payments."
The price of Fuzeon was a shock when it was announced last year despite explanations that it was the first of a new class of HIV drugs called entry inhibitors, and a drug that was extraordinarily difficult to manufacture. Amid much acclaim, Fuzeon received its approval in the spring of 2003, but acceptance by doctors and patients since then has been disappointing and sales have lagged. As the first example of a new technology, Fuzeon was never expected to be perfect, and the HIV treatment community was looking forward to the arrival of a next-in-line drug from Trimeris, code-named T-1249 (Fuzeon had been T-20). T-1249 promised a few improvements over its older sibling, mainly once-a-day injection instead of twice daily, and a resistance profile that could rescue people who with virus that had become resistant to Fuzeon.
There was sadness but no real surprise when Roche/Trimeris announced just after the new year that the one ongoing clinical trial of T-1249 was being halted due to emerging uncertainties over its formulation and manufacturing profile. Trimeris and Roche say that they are not abandoning AIDS but rather retreating to look for better ways to administer peptide-based fusion inhibitors. If they can come up with a drug that only requires one shot a week, no mixing and no refrigeration -- all at a reasonable price, most observers think the outlook for these drugs would brighten considerably. But any such step forward is still years away.
If all this seems gloomy, it might be worth imagining what treatment might be like in the year 2010. There are oral entry inhibitors now in early clinical trials that, if and when they achieve approval, might bring big improvements in tolerability and strength. Since entry inhibitors work on the outside of cells, they are not expected to cause the sort of toxicities that the current generation of drugs do. Also, since they keep cells from becoming infected there may be immunological benefits to increasing the pool of uninfected cells. Protease inhibitors, while effective at reducing viral load, only work on cells that have already been infected. Also, there are reports of some experimental drugs with such long half-lives that they may only need to be taken once a week. Short of a cure, an ideal regimen might keep HIV completely suppressed, preserve uninfected T-cells, be easy to take, have no long-term side effects, and cost little more than cable TV. This is all speculation, of course, but one can hope -- and work to make it a reality.
Back to the GMHC Treatment Issues December 2003 contents page.