The Norvir Switch
Physicians' counseling may hold the key
to patient adherence for the switch from capsule to liquid.
Mark Schoofs is an AIDS and science reporter for The Village Voice
It seems like a small thing. Because of a production problem, Abbott Laboratories' protease inhibitor Norvir (ritonavir) will be available only in liquid, not capsules, for an indefinite period of time. But interviews with more than 25 doctors and patients suggest that if this relatively minor change in therapy isn't managed vigilantly, it could sabotage successful treatment.
Consider John Lyle, a patient who took the liquid form back in 1994 and has been taking the capsules ever since; hearing that he would have to go back to drinking Norvir, he says, "sent me into quite a panic." Lyle participated in the famous study by Aaron Diamond researchers David Ho, MD, and Martin Markowitz, MD, that proved HIV replicates at staggering rates-up to 100 million new virions per day. But that trial sticks in Lyle's mind for a rather different reason. The protocol required patients to stay in the hospital for the first few days, so Lyle received Norvir from a nurse. "I should have realized something was wrong when they came bearing a beaker and a bar of chocolate," he recalls, chuckling. "But I thought, 'Here's the miracle drug that's going to save my life.' So I took the beaker and gulped down the medicine-and it was the most vile thing I have ever tasted. Just ghastly. To this day I have a Pavlovian gag reflex every time I think of it."
Not surprisingly, as soon as Lyle was discharged, he started skipping doses right and left. He told the study doctors that he couldn't take the medicine, but, he recalls, "They said, 'Oh please try, you must try.' And so I lied. I told them I was taking it but I poured it down the drain." It was only when Lyle's viral load spiked back up that the doctors realized he wasn't adhering to the regimen. They removed him from the protocol, he says, until capsules became available.
As Lyle's story makes plain, the terrible taste-and, worse, the lingering, hours-long aftertaste-shouldn't be dismissed as a mere inconvenience. Rather, it should be conceptualized as a side effect like any other, requiring preparation and management by both doctor and patient.
True, repulsive taste is hardly the worst adverse effect of HIV chemotherapy, but it does force doctors to walk a thin line. They must stress the best medical course-which, if a ritonavir regimen is successfully suppressing HIV, is to stick with Norvir and take the liquid, taste be damned. (The liquid formulation has the same antiviral potency, side-effect profile, and bioavailability as the capsules.) But if doctors apply too much pressure to continue with Norvir, patients may lie about adherence, with disastrous consequences. "What I definitely wouldn't want to do is make people feel their concerns are not valid," says Kenneth Mayer, MD, chief of infectious diseases at Memorial Hospital of Rhode Island. "The key is communication," agrees Keith Henry, MD, director of the HIV clinic at Regents Hospital in St. Paul, Minnesota. "I don't want patients to worry about upsetting me."
In addition, there are subtler problems that the change to a liquid might produce. The syrup is 86-proof, and some recovering alcoholics might balk at taking the syrup for fear it could trigger their addiction. Patients who are not open about their HIV status may worry that drinking a medicine will make them more conspicuous than popping a few pills. Then, too, anything that alters patients' medicine-taking routines can undermine adherence.
Finally, the change may spark anxieties in many patients, even those who are willing and able to tolerate the liquid. "People get almost superstitious when a regimen is working," says long-time AIDS activist Mark Harrington of Treatment Action Group. "Psychologically this kind of change is a big deal." Some fear that rival drug companies will fan these anxieties through what Cornelius Baker, executive director of the National Association of People with AIDS (NAPWA), calls "whispering," the surreptitious dissemination of doubts and questions about Norvir, whether Abbott can be trusted to manufacture the liquid properly, and how long it will be until the capsules are back. Given all these factors, says David Moore, MD, a Chicago physician who has been treating people with HIV since 1982, "Some patients will hold their breath until they see their next viral load."
"Absolutely," says Jeff, a ritonavir patient who asked that his last name not be printed. Switching to the liquid, he says, "is like taking a new drug. Maybe it's not like that to doctors, but to the common lay person it is."
Try a nip yourself. "That's been my custom since the old AZT days," says Henry. "It helps when I tell patients I've tried it. So many of them have this view of physicians as disconnected, like we're stockbrokers or something."
About a third of doctors interviewed for this story had tried the medicine. "The worst liqueur I've ever had, laced with motor oil," says Michael Saag, MD, professor of medicine at the University of Alabama and director of the HIV clinic there. The drug, notorious for its gastrointestinal side effects, upset Henry's stomach for two days. Heiko Jessen, MD, who sees many HIV patients in his private practice in Berlin, Germany, says he found the aftertaste so terrible that if he was a patient, "I would rather switch medicines than have this taste all day long."
This reporter tried to take 400 mg-the recommended dose for patients on the popular ritonavir-saquinavir dual-protease regimen-but I didn't finish even that teaspoonful. Mixing it with chocolate milk, a common recommendation, did not mask the taste but merely fouled the milk. Two hours later, the taste was still present, making me feel like I had eaten something vaguely unwholesome. The idea of quaffing the orange, oily syrup twice a day for weeks, perhaps months, was more than daunting. It was depressing.
Of course, taste is subjective: Charles Farthing, MD, medical director of AIDS Healthcare Foundation in Los Angeles and chair of the IAPAC Norvir Advisory Committee, expects "only a small minority of patients" to be unable to tolerate the liquid. Indeed, two of Jessen's patients prefer the liquid to the capsules, and despite Jessen's own intense dislike of the syrup, he will definitely recommend patients try it rather than switch to other drugs. But the taste shouldn't be underestimated. Most doctors said only a few patients had called them, worried about the change. But Markowitz, who conducted several early studies with the liquid formulary, says "all of our old patients" called up, worried about the capsule problem. Like Lyle, they had participated in studies that used liquid ritonavir and, says Markowitz, "They don't want to take it again. It was that bad."
In counseling patients about drinking the liquid, doctors are bereft of the best incentive-a clear date when the capsules will be back. "People will put up with the terrible taste if they know there's an end in sight," notes Stephen Becker, MD, a veteran San Francisco AIDS physician in private practice. He knocks Abbott for not announcing a target date, as do many others. "The company is going to have to come up with some timelines," asserts NAPWA's Baker. "Saying they don't know just doesn't cut it."
Abbott responds that the timeline is not wholly in its hands; the US Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products must certify that the company has rectified the problem. But John Leonard, MD, Abbott's vice president of pharmaceutical development and the scientist who led the development of ritonavir, gave an encouraging progress report, saying, "We're pretty confident we know how to solve the problem."
Most reports have focused on the crystallization problem. (Crystallized ritonavir is absorbed into the body less efficiently.) The company does not know what has caused this problem, but it doesn't need to solve this mystery. Instead, it can pull an end-run by developing a different formulation. To get into the bloodstream, the molecule that blocks HIV's protease enzyme must be dissolved in a "solvent." Something happened that allows the molecule to crystallize in the solvent used in capsules, though not in the slightly different solvent used in the liquid. Now, Abbott is trying to develop a new solvent for capsules that will prevent crystallization, no matter what the production problem is. "We believe we know how" to do that, says Leonard, but it will require testing, regulatory approval, and revving up to large-scale production.
Leonard won't give a timeline, partly to avoid appearing to pressure the FDA for hasty certification, and maybe to avoid larger consequences. When the problem first arose, in mid-June, the company thought it could fix it without suffering a lapse in production. Clearly, they were wrong then, but they cannot afford to be wrong now. If Abbott doesn't meet a publicly announced deadline -- or, worse if it releases new capsules that it is later forced to recall, it would create tremendous distrust by patients, and on Wall Street. So Abbott will want absolute certitude that all of the kinks are worked out before putting new capsules on the market.
Bottom line: Doctors and patients must switch to the liquid without knowing whether they are making the change for weeks or months. (While doctors universally recommend staying on Norvir for patients doing well on it, many doctors said they are postponing starting patients on ritonavir, at least until Abbot provides a timeline.)
With no light at the end of the tunnel, what other counseling strategies can doctors employ? David Butcher, MD, is medical director of the Kansas City Free Health Clinic, and is developing the adherence section of the IAPAC Norvir Advisory -- says his clinic spends "a lot of up-front time" educating patients about their options and the importance of adherence before they ever take their first pill. He plans to deal with the ritonavir situation in the same proactive way, listening to patients, identifying their particular anxieties, and then addressing them. "That in itself," he says, "is enough reassurance and comfort for people to get through most things."
He describes one patient who was very worried about the taste of liquid ritonavir. Butcher stressed the risks of changing drugs-but he pointed out that the danger included more than the potential for HIV to escape a new regimen. "We discussed how changing medicines might cause new side effects, which could be worse than just adding on a nasty taste," Butcher says. This devil-you-know strategy worked: The patient has been on the liquid for a week and is doing well, says Butcher.
Like most physicians, Butcher also dispenses practical tips to avoid liquid ritonavir's terrible taste, from mixing it with chocolate milk, to coating the tongue with peanut butter, to using a syringe to squirt it down the back of the throat and bypass the taste buds altogether. Other recommendations: Suck on a popsicle to numb the tongue, a technique that many children who take Norvir liquid use with remarkable compliance. Another option: Use a straw, again to avoid the taste buds, and follow the medicine with peppermint candies or Reese's peanut butter cups. Abbott has been providing free chocolate Ensure (which is made by an Abbott subsidiary).
Perhaps the most innovative method for avoiding the taste comes from Calvin Cohen, MD, research director of the Community Research Initiative of New England and a leading Norvir clinical researcher. He suggests patients prepare their own capsules by putting Norvir liquid into do-it-yourself gelatin capsules. He insists that, armed with a dropper, a patient can prepare his or her entire daily regimen in just a couple of minutes. Is this workable? Cohen answers, "The FDA won't let Abbott talk about this option because there haven't been clinical trials with gel caps." But he adds, "There's every reason to think it would work, because gel caps are well known to dissolve in people's stomachs. Indeed it is being recommended that ritonavir be taken with food."
Butcher says that handing out Ensure and a list of tips to mask Norvir's taste is the equivalent of prescribing Imodium
to control GI side effects: Both are tangible, effective tools to cope with discomfort, and both give patients the sense they are being cared for, that they are not in this alone.
Abbott says approximatelyl 65,000 patients are taking ritonavir. In the practices of the physicians interviewed for this article, by far the majority of patients on ritonavir were taking the drug in combination with saquinavir, usually after failing one or more protease inhibitor regimens, or because they had extremely high baseline viral loads. Such patients usually know that their options are
limited, and "those with a good response will be motivated to continue with ritonavir," says Michael Giordano, MD, director of the Cornell Clinical Trials Unit of New York Hospital/Cornell Medical Center in New York City. "They will do just fine, as long as we give them reassurance and education." Crisply, he lays out the pros and cons: "The pro is pills are easier than liquid. The con is that you would have to switch drugs. But no protease is more effective than ritonavir. No protease is truly twice a day. And responses to proteases are occasionally idiosyncratic, so you shouldn't mess with a good thing." And in case any patients worry about the drug's potency, he notes that "liquid ritonavir was used in one of the most dramatic studies in the history of AIDS, (Abbott 247), which showed that ritonavir dramatically extended life in very sick patients.
Ramón, who prefers not to give his last name, was a patient in that study. He had suffered Pneumocystis carinii pneumonia, Kaposi's sarcoma, and other opportunistic diseases, and he credits Norvir with saving his life. Even though "the happiest moment in my life was when ritonavir came out in capsules," he says he will take the liquid when his pills run out because changing drugs "could be a deadly mistake." Many other patients feel similarly. Michael Warner of New York City takes ritonavir, saquinavir, and two nucleoside analogs--a combination which has kept his virus undetectable for more than a year. He is dreading the liquid but says, "It would be crazy to change drugs over something like this." Colin Kovacs, MD, of Toronto, Canada, is both an HIV physician and patient. He has been on Norvir for more than two years, and says that horrible taste is "a small price to pay for a longer life." Even Lyle, the patient who poured the liquid down the drain, says he wouldn't risk changing his drugs. "Yeah," he says with a sigh, "I would drink the poison."
Of course, some patients will balk at the taste. Steven Deeks, MD, assistant clinical professor of medicine at the University of California at San Francisco AIDS Program, has a patient who tried the solution "a couple of years ago when he was going on a trip and wanted something that did not need to be refrigerated." Now, the patient is "very anxious" about the liquid, which he couldn't stomach, and wants to switch. Deeks counseled him on the benefits of sticking with Norvir but, ultimately, a drug can only work if a patient takes it. "So we're going to struggle to come up with another drug combination," says Deeks.
There are other reasons patients might want to switch regimens. The easiest cases will be those like Patrick Gillespie, a patient in Anaheim, California. For two years, his ritonavir regimen had suppressed his virus, but then a recent viral load test showed 30,000 copies. The very next week, he heard that Norvir would only be available in liquid, which has fortified his urge to change drugs. "With the sudden spike in my viral load, this regimen obviously isn't working anymore," he says. "So why waste the time? Let's jump now."
Greg Lugliani, director of communications for Gay Men's Health Crisis in New York City, presents a murkier case. Ritonavir has kept his virus undetectable for eight months. Still, he says, "I was thinking of switching to one of the NNRTIs anyway because my cholesterol is very elevated." That's a common side effect believed to be caused by protease inhibitors, but no one knows how severe it is. Lugliani's high cholesterol could lead to coronary problems, or it could be a precursor to what's been dubbed "lipodystrophy," a loose collection of symptoms that often includes the redistribution of body fat into a "protease paunch" and the elevation of blood lipids and triglycerides. But then again, cholesterol-lowering medication might be all that's needed, allowing the regimen to continue working. The plain fact is that no one knows-but Lugliani is clearly worried about his cholesterol. He says the switch to ritonaivir liquid "might be a good catalyst" for changing his regimen.
And then, there's a patient that Roy Gulick, MD, recently talked with. Gulick, assistant professor of medicine at New York Hospital/Cornell Medical Center, says the woman had already been on two previous regimens, one containing indinavir and the other containing nelfinavir, and she had recently failed a combination containing an NNRTI. So, Gulick devised what he calls a "fringy" salvage therapy: ddI, d4t, hydroxyurea, saquinavir and ritonavir. "That's a lot of pills," Gulick says, "so we talked it over carefully, and she had researched some things on her own. Finally, she agreed to it. And then this ritonavir thing hit."
The woman is a recovering alcoholic and, Gulick recalls, she "called a nurse and said, 'I've taken two doses, I feel drunk. I haven't touched alcohol in five years, and I don't want any alcohol in my system.' So I called her and explained that we have very few treatment options left." As of press time, Gulick and his patient had postponed addressing dilemma. Gulick found a pharmacy that still had capsules, buying the patient an extra month. Gulick doesn't know what she will decide to do-or what regimen he will recommend if she refuses to drink Norvir.
Most doctors feel that objections to the syrup's alcohol content will be rare, partly because the capsules contain some alcohol, too, though less than the liquid. "I'm not worried about this," says Henry, who has a high percentage of patients with substance-abuse problems. Like many physicians, Henry notes that patients would only be taking a teaspoon at a time, too small an amount to trigger cravings in most recovering alcoholics. Don Des Jarlais, PhD, is a veteran substance abuse researcher at New York City's Beth Israel Medical Center, and is developing the the alcohol issues section of the IAPAC Norvir Advisory. He agrees that "the quantity is so low that you would expect no noticeable physiological response." But he's quick to caution that "the psychology could be extremely complicated. Somebody who believes he has to be completely clean and sober might say, 'I can have this alcohol [in the ritonavir], so maybe I can go up to a drink a day.'" How common will that problem be? "I honestly don't know," he says.
Henry, however, has another reason for believing Norvir won't make most recovering alcoholics fall off the wagon: "Ritonavir has a built-in Antabuse
effect," he says. "It makes you feel lousy, and it tastes bad. So it would be the unusual alcoholic who would be looking forward to this." Laughing, Des Jarlais says, "That's actually a good point. Taking this stuff is not self-reinforcing. You don't take it and decide it feels so good you'll take more." Nevertheless, both doctors agree that there will be some patients like Gulick's.
If changing drugs is necessary, what regimen should patients switch to? "You cannot answer this generally," says Jessen. Indeed, treatment history, ability and willingness to adhere to complicated regimens, secondary diseases, HIV resistance testing, clinical status, and, of course, viral load and CD4 counts all factor into the decision. "We can't be cavalier," says Cohen, noting that some patients have burned through every drug. Even for those who haven't, he says, "there's always a chance a switch won't work. But if someone says, 'I'm miserable and I can't take this drug,' then we have enough options to at least think about switching."
In extreme cases, when no other treatment options exist and the patient cannot tolerate Norvir liquid, physician and patient might consider ceasing all anti-HIV medication until Abbott resumes production of the capsules. Theoretically, stopping cold-turkey should not induce viral resistance, though of course it would allow HIV to resume its slow destruction of the immune system.
Just as the taste of liquid Norvir could be considered a side effect, so switching to the liquid should be conceptualized as a change in medication-with all same the potential for inciting anxieties and rattling adherence. Jeff, the patient who says that lay people will certainly see the change this way, even if physicians don't, has a lot of worries about converting to the liquid. He's not open about being HIV-positive, yet he's often at his coffee-shop job when it's time for his evening dose. Taking pills there "isn't a big deal," he says, because he can take them quickly and unobtrusively, and if anyone asks what they are, "I can say they're vitamins." But he worries that "it would be much more obvious if I were pouring something out of a bottle." Jeff also hasn't told his parents about his infection, so he worries about drinking ritonavir when he's home for the holidays or even when he's out to dinner with friends.
Warner, the New York City patient, worries about adherence. "My routine is worked out pretty well with pills," he says, "and routine counts for a lot when you have to comply on a daily basis. It's so easy to forget when you're routine is disrupted." Indeed, studies show that patients are more likely to miss doses on weekends and holidays-precisely the times when their routines change.
"I'm not sure liquid Norvir is the issue, but rather people being in a pattern," explains Cheryl Mchunguzi, an HIV educator and case manager with Harlem Congregations for Community Improvement, a program of 100 New York City African-American churches. Most of her clients, she says, "don't want AIDS to be the center of their world. But when you mess with the dynamics of medicine, then it becomes the focus again." It's important, she says, to keep checking in to see how the change is being incorporated. "After we go over their regimens, explaining how many yellow-colored pills to take and when to take them, patients leave and they manage their care. A lot of times we do not know how they're managing it until they go back to their doctor."
That's exactly why many doctors, before initiating HAART, recommend patients go through a two-week "trial run," taking different colored jelly beans at the times they'll be taking their pills. Similarly, doctors could have patients do a practice run with a liquid-carrying it with them, shaking it before measuring out the right amount, mixing it with chocolate milk or putting it into homemade gel caps, and so on. It's important, says Moore, the Chicago physician, to minimize "all the quirky ways people get destabilized by change-you know, just when you have your life figured out, then have to change it again."
With HIV patients, anxiety is always there. Listen to Gillespie, who has known he is HIV-positive for a full decade. "I'm very nervous about drugs that haven't been around for long," he says. "Especially with protease inhibitors, I'm sort of the guinea pig. They're learning off of me. It's not that I'm not grateful, but if something goes wrong, I become a statistic. Now we're seeing cross-resistance, protease paunch, buffalo humps, people who don't respond at all. So I'm apprehensive, and now one of my worst nightmares has come true, a problem in production. What went wrong with pills, and how do we know that hasn't gone wrong with liquid, or won't in the future?" He laughs wryly and says, "Chronic manageable disease? Hmmm."
Such anxiety lives in almost all patients, like embers that never go out. And a change in the very drugs that are keeping the virus at bay can ignite their fears. Jeff, for example, has been assured the liquid is as potent as the capsules, yet he still wonders whether it really will work as well. Jerry, a patient in Irvine, California, who has been on ritonavir for only about two months, has a similar concern. "My pharmacist says there's no reason the liquid should act differently, but I'm somewhat skeptical," he says. "Liquid forms are generally more immediate in their results, so it might agitate my diarrhea a little more." Margaret Ricks, a patient in Oakland, California, has never been an alcoholic, but she's worried about the syrup's high ethanol content, because alcohol upsets her stomach and gives her headaches.
Are rival drug companies exploiting this vulnerable moment to try to sell their drugs? Salespeople certainly have an incentive; they receive bonuses or commissions based on how much drug they sell. Nevertheless, the vast majority of doctors report that marketing representatives have not crossed the ethical line. "I haven't seen reps from other companies coming by and rubbing their hands with dollar signs in eyes," says Henry. "Honestly, I'm not aware of any companies using this to try to steal business away," concurs Glen Peitrodani, RPh, chief pharmacist at the Walgreens pharmacy located in Howard Brown Memorial Clinic, the largest AIDS service organization in Chicago. "The drug reps I have seen are trying to be nice with Abbott, says Pablo Tebas, MD, assistant professor of medicine at Washington University in St. Louis, Missouri. Their motivation, says Tebas, may be self-interest: "What happened to Abbott could happen to them."
Giordano, however, contends that "other companies are taking this as a marketing opportunity, which is quite unattractive." He says the sell can be subtle: "A rep from Merck asked me if I would recommend the timing by which one could switch from ritonavir to indinavir [Crixivan]" There's no reason for a marketing employee to ask that question, Giordano says; that's why companies have scientific divisions. Deeks says, "No one has crossed the line with me, but sure, it's happening in the community."
Merck spokesperson Kyra Lindemann says that the company does not interfere with treatment decisions, which should be "strictly up to the patient in consultation with his physician." She says she has no knowledge about the specific interaction with Giordano, but says, "The only thing I can think of is that the rep wasn't trying to suggest a switch, but was really trying to do some fact finding and see what doctors are seeing in the real world." When the ritonavir problem broke, she says, Merck originally thought that if patients did elect to switch to indinavir, it might be necessary to have a washout period because of ritonavir's effect on the liver. After reviewing the science, Merck has concluded that no washout period is required.
Giordano also notes that Stadtlanders pharmacy has circulated a chart showing options for switching. "I'm sure it's all fine, but I promise you that Merck and Agouron have jumped on that." Stadtlanders refused to release the chart to this reporter, saying it was meant only for doctors and pharmacists. (IAPAC, however, will be including the Stadtlanders algorithm along with the Fortovase algorithm in the IAPAC Norvir Advisory.) Merck and Agouron both deny they have exploited recommendations for switching. Agouron spokesperson Joy Schmidt says the company has provided updates on studies involving its protease inhibitor nelfinavir (Viracept), but in doing so, she says, the goal is to "responsibly respond as opposed to being a vulture."
Roche Laboratories, makers of saquinavir (Fortovase and Invirase) raised eyebrows be sending out a flyer prepared specifically for the current problem with ritonavir. Headlined "Attention Norvir (ritonavir) prescribers and dispensers," the flyer went to doctors, pharmacists, and AIDS service organizations. It states, "Patients should be encouraged to continue ritonavir. However, the change in form of their medicine [from capsules to liquid] may affect the ability of some patients to tolerate or adhere to therapy. For these patients, Fortovase (saquinavir) may be a good alternate..." The flyer resulted from a "breakdown in communications," says Robert Posch, community development director for Roche Laboratories. "Somebody in marketing unilaterally sent that out. It didn't go through our internal review processes." He adds, "No company should be jumping up for joy [over Abbott's troubles]. There is no data to tell us what to do" if patients cannot tolerate Norvir liquid.
Even without other companies exploiting Abbott's woes, NAPWA's Baker says "the run-over effect" of the manufacturing problem could be a deepening of the distrust many patients already feel toward antiretroviral drugs and pharmaceutical companies that make them. With all the side effects that have been emerging, and the increasing failure rates of combination therapy, a manufacturing problem like this could deter patients from starting medication.
"My big question," says Ramón, the patient who believes he was saved by enrolling in an early ritonavir trial, "is how could this happen?" That sounds familiar to Kenneth Mayer. "A lot of my patients say, 'This is a big company that's been making this drug for a while, so how could there be a problem like this?' It's undermined their feeling of trust." Ever the dry wit, Lyle quips, "I sure hope they haven't lost the recipe."
Finally, the change from capsules to liquid, seemingly so simple, could cause another long-term problem: delayed or weakened data about how to use new drugs and combinations. Saag says one of his trials that was about to start has been postponed because of Abbott's manufacturing problem. Gulick, the national chair of AIDS Clinical Trial Group study 359, which compares various salvage regimens, says his study has a seven-month supply of capsules banked up. But at a recent ACTG meeting, that fact caused tension, as other studies didn't have such a large inventory. Gulick's study agreed to share with a pediatric trial nearing completion; another study, however, will run out of pills in about one month.
Switching from capsules to liquid in a trial is "potentially a very serious thing," explains Gulick. "If the liquid is more poorly tolerated, you will have a dropout you didn't have before. That could really impact on your ability to say anything about the different arms in a trial." For example, he says, "it might make saquinavir-nelfinavir look better" than it really is.
Still, if Abbott can bring capsules back quickly, Mayer thinks "all will be forgiven." But perhaps not forgotten. "How vulnerable are other drugs?" wonders Giordano. "This hit us completely by surprise. Doctors and patients think the supply of medication is forever and nothing can happen. But that's not necessarily true, especially for protease inhibitors, which are very complicated to make." Henry concurs, saying, "I view this as fallout from the rush to get improved drugs out. When drugs get pushed out quickly, everything isn't understood. We will encounter more problems like this."
Henry continues, "This is a real hassle, but it's not close to the worst thing that's happening. Are we going to get through it okay for most patients? Yes." In fact, says this 13-year veteran of treating HIV, it's actually "pleasant to be worried about the flavor of Norvir instead of people dying. I'll take this any day."