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2000: A Year of Endings and Beginnings

By Mark Milano

January/February 2001

2000 finally saw the end of "Hit Hard, Hit Early." People had been questioning the early use of antiretrovirals for some time, but when Dr. Anthony Fauci, head of NIAID, gave a plenary speech at the Durban AIDS conference and said, ". . . prolonged courses of continuous HAART are not an option . . ." he sounded the death knell, in my book. While he was talking about STI's (structured treatment interruptions), the inference seemed clear: if you can't stay on antiretroviral treatment forever, make sure that you don't start it until you need it. The NIH has been trying to design a "when to start" trial for some time now, but there are obviously many difficulties and opposing views to overcome. So, until we have data from that trial or one like it, the message seems to be that people with HIV should begin taking treatment when they need it, and not before.

Of course, there are different ideas as to when that is -- some people think anyone below 500 CD4s needs to start therapy, others would wait until you're closer to 200. For me, the most important factor has always been the "trend over time." Have you been stable at 350 CD4 cells for some time? Then maybe it's smart to wait. Are your CD4s lower each time you check? Maybe it's time to start. I'm not proposing any answers to this truly unanswered question, but the new information about long-term side effects has shown us that starting everyone on treatment as soon as possible is not the answer. When we have drugs that are effective and truly safe in the long-run, everyone will take them. But for now, the word is: wait 'til it's time, and wait until you're ready to make a long-term commitment to adherence.

Structured Treatment Interruptions

STIs began to be taken seriously in Durban. Fauci presented some interesting data and theories about why stopping treatment for controlled periods of time may be beneficial. Here's the theory he presented: one thing that has been found in Long Term Non-progressors (LTNPs), is their abundance of HIV-specific CD4 cells, cells that specifically target HIV for destruction. In almost all people with HIV, these cells are destroyed early in infection and never return. One reason they don't return even in people who respond well to treatment is that they don't have enough HIV in their body for the immune system to respond to, so no HIV-specific cells are produced.

People who stopped treatment in Fauci's report saw their HIV viral load increase significantly, and then return to undetectable once treatment was restarted. But when treatment was stopped a second time, the virus rebounded to a lower level than before -- a new "viral setpoint" had been established. Another interruption, after a few more weeks on therapy, and another, lower, viral setpoint. The hope was that the return of the virus was stimulating the body to produce those invaluable HIV-specific CD4 cells. Fauci concluded by raising the hope that all people with HIV could be turned into LTNPs if we could just find the right STI system.

Well, like all fairy tales, this one doesn't quite work in the real world. First, not all patients respond well to STIs -- some don't see lower viral setpoints. And while Fauci showed that three of his patients had more cytotoxic ("killer") T cells, another study showed that STIs did not increase HIV-specific CD4 cells, as hoped. Moreover, all STI work has been done in very small numbers of people, usually less than 20 per study, so it's impossible to extrapolate these findings to the larger population.

Here's what we know: some people can go off therapy for a short period of time and then restart, without developing resistance or doing permanent damage to CD4 counts. But this message comes with important caveats: drugs must be stopped together (and with drugs like Sustiva staying in the body for days after the last dose, this can be tricky), viral loads will rise and CD4 counts will drop when the drugs are stopped (so if your CD4 count is already low, you may risk developing an opportunistic infection), some people with viral loads above 100,000 have had a hard time returning to undetectable, and finally, no confirmed benefit has been shown so far, other than giving the body a respite from the long-term side effects of these drugs.

But that's not such a bad thing, so researchers are looking carefully at how STIs can be used to give people a break from their drugs and perhaps even boost the body's own immune response to HIV. The safest thing right now is to wait until more data is in, but if you are thinking about an STI, be sure you do it with your doctor, and with a doctor who is on the cutting edge of research. Like they say on TV: "Don't try this at home."

New Treatments

2000 was largely a year of "more of the same" when it came to treatments. No ground-breaking new drugs, just small steps, like a new protease inhibitor (Kaletra) that seems to work in people who are resistant to other PIs, and a new form of an old drug (ddI), that is swallowed rather than chewed. Gilead finally pulled the plug on their ineffective, kidney-toxic drug (Preveon -- this drug looked bad back in 1998), and pushed forward on a better, less toxic version (tenofovir). Boehringer-Ingleheim bought another PI (tipranavir) from Pharmacia-Upjohn, and was sent back to square one -- finding the right dose! Roche teamed up with Trimeris to finally move their fusion inhibitor (T-20) into larger trials, but the company is claiming that low drug supplies will hinder attempts at a large scale Expanded Access program. (Hmm -- where have I heard that before? Can you say "ritonavir?")

Money for Patients

2000 saw the beginning of a disturbing trend: the increasingly common practice of paying doctors large fees for each patient they enroll in a clinical trial. One of the hallmarks of clinical research has always been that patients in trials received their primary care outside of the trial setting, so they always had a care provider who put their interests ahead of the research. But when your doctor has a financial stake in getting and keeping you in a trial, can you be sure s/he has no conflict of interest? I hate to say it, but I've heard horror stories: patients who didn't know they were enrolled in a trial, patients pressured to join a trial they weren't really interested in, etc.

Let's be clear: clinical trials are important for both individual patients and the general population. A trial can provide early access to new treatments and to cutting-edge researchers and lab tests. But no one should ever be pressured to join a trial they aren't interested in, and everyone in a trial needs an outside advocate to watch their butt. If you join a trial, do it with your eyes wide open and ask lots of questions. Many of my friends are alive today because they enrolled in clinical trials, but make sure it's right for you before you do. And maybe you could ask your doctor to split that finder's fee with you!

Drugs for Africa

Durban also saw the beginning of a new hope: the realization that treatment was a possibility for poor nations, if the drug companies and the U.S. government would stop fighting their legal efforts to produce generic versions of lifesaving meds. I joined a group of activists that hounded candidate Al Gore until he pressured the U.S. Trade Representative to change trade policies regarding nations that produce generic drugs without the permission of the patent holder. We won that battle in time to see South Africa's president Mbeki drop plans to begin making these drugs and start questioning whether HIV causes AIDS!

That was disheartening, but our work did lead generic manufacturers to finally reveal what we had suspected for years: that a three-drug combo could be produced in large quantities for less than $300 a year! That's right -- the same drugs we pay over $12,000 for could be made available to poor nations for a fraction of what we're charged for them. Now, no one denies that drug companies have to charge more than their manufacturing costs in order to make a profit (just how much they really have to mark-up the price is something I won't go into here), but when 33 million people are facing death in poor countries, it's clear that they shouldn't be paying for that research, especially when even the WTO recognizes the rights of sovereign nations to override patents in times of national emergencies.

This message came through loud and clear from numerous speakers and protests at Durban: treatment is a real possibility for people around the world, if we can get the generics made. And for those who claimed that the health infrastructure isn't there, a number of health workers made this point: Treatment drives infrastructure. When treatments are available, the clinics and doctors to administer them follow. We've had enough clinics in poor countries with no drugs in their pharmacies. Why not try the reverse for a while and see what happens? The workers in the field, including organizations like Doctors Without Borders, say that making treatments available is an important first step.

It's time for people with HIV in the U.S. to realize that as bad as it is for us (and let's not pretend it isn't bad -- I lost a number of friends this year), it's incredibly worse for people overseas. And it's not a case of "it's just too big to get a grip on." There are specific things that we can work on here to improve access over there. Urging the drug companies that may be saving your life to stop opposing efforts to save lives in Africa would be a good place to start.

Mark Milano, formerly with the New York State health department, is a longtime member of ACT UP/New York.

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