The Positive Side

Summer 2007 

Staying on the Road to Health

More and more studies show that the route to optimal health for anyone on meds is adherence: you’ve got to stick to your demanding drug regimen. We ask the experts — doctors, researchers and PHAs — how to stay on track.

By David McLay

WHEN IT IS TIME to start a regimen of anti-HIV medications, the most obvious need is finding a drug combination that will bring your viral load down, ideally to an undetectable level. But there’s a second consideration that’s just as important: being fully committed to taking the drugs. The act of taking your meds as prescribed and directed is called “adherence,” and as we gain more experience with these drugs, experts and people with HIV/AIDS (PHAs) are gaining new understanding of how it all works.

Medical experts preach adherence, insisting that anti-HIV meds — generally known as HAART (highly active antiretroviral therapy) — always need to be taken at exactly the right time and in exactly the right way. If not, there’s the spectre of a resistant virus, which can lead to the need to switch meds, which ultimately limits treatment options.

Studies have revealed that PHAs must take their pills correctly 95 percent of the time for drug levels to remain high enough in the blood to block the virus from replicating. (That’s one missed dose per month of a once-a-day regimen, or three missed doses of a twice-a-day regimen, though research is showing that some drugs might be more “forgiving” than others.) If adherence drops even a little bit, say, down to 85 percent (four missed once-a-day doses per month, or nine missed twice-a-day doses), drug levels enter the danger zone, where the virus can replicate and become resistant. And taking a dose late can have the same effect, meaning that not only is it important to take your medication, it is also important to take it at the right time.

The push for adherence is based on pharmacokinetics (a fancy word for how a drug behaves in our bodies) and our lab-based understanding that the virus is only held in check under certain very stringent conditions. One serious challenge with this medical view of adherence is that it doesn’t take into account the fact that PHAs will be popping pills every day for years and years. Take Bill, for instance: he’s 55 and has been HIV-positive for about 25 years. He started meds in the mid-1990s. That means that by now he has taken at least 40,000 pills. With recent advances, experts predict that, like Bill, many PHAs on treatment can live out their natural lifespans, which is obviously a great step forward. For Bill, who has many years ahead of him, it means thousands of more pills. The challenge for Bill and for every PHA on anti-HIV therapy is to find the stamina to stay adherent.

Pill-popping prep

Adherence seems like one of those things that would take the most effort once you begin treatment. But experts are beginning to realize that there is a lot of work to be done before the first pill is popped. Getting ready and committing to the therapy before starting it can help people adhere in the long run.

This idea is called treatment preparedness. On a practical level, this commitment can mean answering yes to questions such as “Can you adjust your schedule to fit pill-taking in at regular intervals, regardless of where you are?” and “Can you ride out the side effects that will invariably occur during the first couple of months?” But sometimes, it’s the questions behind these questions that can play a bigger role in staying committed to HAART. What does it mean to start HAART? What fears and expectations are raised by the idea of starting HAART?

Bill lived through his own version of becoming prepared for treatment. When AZT first became available in the mid-1980s, he refused to start because he wasn’t ready to take pills for the rest of his life. But he made a deal with his doctor — he promised to start treatment if his CD4+ count fell below the critical value of 200. About 10 years later, the count reached 175, and Bill knew it was time to start meds. His doctor and healthcare team were supportive, telling him not to start until he was completely ready. Bill took about a week to prepare; during that time, he laid out some of his fears and concerns in a letter to himself. He worried about how the meds would affect his body, especially his liver. And he wondered how he would cope with drug side effects like nausea and chronic diarrhea.

Declining CD4+ counts and high viral loads often trigger talk about starting meds. But not all PHAs have the time that Bill had to prepare. They can feel forced to start meds before they are truly ready. As a result, some end up not adhering because they’re not committed to the treatment plan. A 2006 U.S. study followed more than 3,400 PHAs who were starting HAART to see how many stopped taking meds and why. After following up one year later, researchers found that adherence issues were second only to side effects as the reason given for stopping therapy: about 13 percent of PHAs stopped taking their pills because they couldn’t adhere to their regimen.

Accepting the importance of taking meds is not always easy. Anti-HIV meds work in a way that’s contrary to how we usually think about taking medicine. With other illnesses, most of the time we get sick and then take pills to get better. In those cases there’s some immediate payoff for putting up with the inconvenience of adhering. But HAART is the opposite. People are usually not severely ill when they start (though they sometimes have nagging health problems, such as lingering skin infections), and so there is no obvious benefit to be gained right away. Instead they are investing in something intangible — a healthy future. So they are paying now for something they won’t get until later. That’s not an easy sale.

Facing the future

For PHAs who received their HIV diagnosis when they were feeling healthy, starting meds can be the first time that they are facing HIV in a real and concrete way. Gillian Kolla, treatment buddy program coordinator at AIDS Community Care Montreal (ACCM), recounts the story of a client who brought home his first set of meds. He lined up all the pill bottles on the table, and as he sat there looking at his first dose, he said to himself, “This is real.” The emotional issues surrounding a diagnosis of a chronic, incurable condition such as HIV can be difficult to face, and adherence may suffer in the meantime. The program that Kolla runs at ACCM pairs people who are starting or switching a HAART regimen with people already on meds. The goal is to offer personal experience and support through the difficult early days.

Another worry for PHAs concerns how meds will affect their social and personal lives. Disclosure of HIV status can become an issue when taking meds, because popping pills is a very obvious sign of sickness. And many people, while sincerely concerned, end up just seeming nosy. Often, PHAs who aren’t on meds don’t show any sign that they have HIV, and so it is easy to maintain control over who knows and who doesn’t. And there is still a lot of stigma around HIV, so it does matter whether or not someone knows. When looking for ways to deal with disclosure, AIDS service organizations and other PHAs on meds are good resources.

Thrown into this mix is the fear of drug side effects, especially the long-term ones. Frequently, some of the more common side effects, such as diarrhea, nausea and headaches, hit hard at the beginning and then subside. But the one that causes more concern is lipodystrophy — the changes in fat metabolism and storage that are estimated to affect 30 to 50 percent of PHAs on meds. Lipodystrophy is sometimes associated with changes in the body shape, especially the loss of fat under the skin (lipoatrophy) that causes the sunken face that many PHAs feel is a dead giveaway of their HIV status. While increased risk of heart disease and diabetes are more medically serious, facial wasting is troubling in another way — it’s like wearing a sandwich board that says: “I have HIV.”

Researchers have discovered that lipoatrophy is most commonly associated with certain drugs, in particular, d4T (Zerit) and, to a lesser extent, AZT (Retrovir). These drugs were common in older combinations, but with new drugs available it might be possible to avoid using d4T. This is something PHAs should take up with their doctor when discussing starting meds. And even if certain problem drugs can’t be avoided, PHAs can watch out for early signs of fat change and be ready to take action. Changing a drug in a combination can help slow or stop fat loss, but an early response is crucial because getting the fat back is a slow process, if it happens at all. There are also surgical options, including injections of “fillers.”

Deciding with doc

The topic of starting meds is a discussion that may last over several doctor visits. But face-to-face time with your doctor is precious and often there isn’t enough of it for a lengthy discussion about all the pros and cons of treatment. Dr. Ahmed Bayoumi, director of the Clinical Epidemiology program at the University of Toronto and a clinician at the HIV clinic in St. Michael’s Hospital, is working to develop a decision aid that will help PHAs decide whether it is a good time to start HAART and what their first regimen should be. The computer-based interactive program will help explore in-depth issues that a physician can’t cover in a brief visit.

The idea of a decision aid comes from research into people living with cancer, which has found that patients who have used this tool when it comes to treatment options are more likely to be comfortable with their decisions. Bayoumi says it is logical to expect that someone who is more comfortable with the decision to start meds will be more likely to adhere.

While the adherence decision tool is still in development, Bayoumi says that it will take in all the key factors related to making decisions about treatment, including apprehension about both short- and long-term side effects, level of commitment to the idea of taking meds, and concerns around confidentiality. Bayoumi says that his own patients “have to be ready for the commitment of taking pills. I do my best to help them understand why they should be taking pills. I explain the risks of not starting meds and the risks of starting them. But they decide when it is time.”

So, what if you’re not ready to start treatment? You’ll no doubt run into some opposition from your doctor, especially if your numbers are getting close to the critical values. In your doctor’s calculation, the risk of serious medical complications increases with every drop in CD4+ count. But your doctor may not see the same risk equation you do. Bayoumi offers a professional perspective: “Doctors like to minimize risk. But some patients are more willing to take risks. If you and your doctor have different ideas about starting meds, you should be able to communicate your thought process to your doctor so she can understand where you’re coming from.”

PHAs and doctors can hold very different views of HAART, according to a 2006 survey conducted by the International Association of Physicians in AIDS Care. The survey asked 400 PHAs and 150 HIV doctors in the U.S. about different aspects of HIV treatment. Sometimes PHAs and doctors agreed, but sometimes they didn’t. For example, 76 percent of doctors disagreed with the idea that drug side effects are worse than the disease itself; only 47 percent of PHAs disagreed that drug side effects are worse than HIV. This might be because doctors have knowledge of the advanced stages of HIV, while PHAs face the immediate distress of daily diarrhea or nausea.

And the reasons for delaying treatment varied too. Eighty-nine percent of doctors surveyed said the main reason for delaying treatment was that the patient’s CD4+ count and viral load did not warrant treatment. But only 27 percent of PHAs said this was their main reason — more important was the desire to avoid side effects (44 percent) and the fact that they were feeling healthy and didn’t have any symptoms (38 percent).

Adjusting the meds

Once the decision to start HAART has been made, prescriptions are filled, pills are put in their dosettes, and the reality of daily pill-popping sets in. Like anything new, it takes some adjusting to take meds every day. But, as Daniel from Montreal puts it: “Adjust the meds to your life; don’t adjust your life to the meds.”

Daniel, 30, was diagnosed in April 2006. He started meds soon afterwards due to falling CD4+ counts and an uncontrolled viral load. Currently, he takes unboosted atazanavir (Reyataz), two pills once a day, and Kivexa (abacavir + 3TC), one pill once a day. He takes all three pills just before going to bed at 10 pm.

Atazanavir is often prescribed with another protease inhibitor, ritonavir (Norvir), in a strategy called boosting. Taking a bit of ritonavir increases the levels of atazanavir in the blood, meaning more potency with less drug. But Daniel experienced headaches and nausea, common side effects from ritonavir. And his liver produced increasing levels of bilirubin, which can cause yellowing of the skin. In Daniel’s case, the bilirubin caused his eyes to turn yellow. He couldn’t handle it. After one month, he and his doctor decided to drop the ritonavir and increase the atazanavir. The side effects settled down, though Daniel still sometimes sees the yellow in his eyes.

Daniel also had a few bumps in his timing schedule. He started out by taking his pills in the morning. He remembered the tip about attaching the pill-popping to something he does every day so that it becomes part of his routine. But he found that the morning didn’t work very well. “Taking the pills in the morning was a reminder that I have HIV, and that was a real downer at the beginning of the day,” he says. “And the side effects were bad, especially at the beginning, and I had to suffer through them in the middle of the day when I was working. If I went out the night before, it was harder to take my pills in the morning. I’d want to sleep in, not get up and take them. So I decided to try taking them at night because then I would sleep through most of the side effects. I’m usually at home in the evening, so it was easy to do.”

Side effects were at the forefront of Daniel’s thoughts even when he was deciding on a course of action. His doctor gave him a couple of options for regimens and listed the potential side effects. Daniel wanted to avoid neurological side effects, so he stayed away from efavirenz (Sustiva); he figured the diarrhea and stomach upset of atazanavir would be easier to handle. His doctor had told him about the low risk of increased bilirubin, “but I freaked out when I saw my eyes,” Daniel says. “I didn’t think about how visible it would be. People asked me if I was OK. I acted surprised. What was I going to say? You don’t start revealing that sort of stuff.”

Daniel gives a lot of credit to the team at the local health clinic. Before starting HAART and for six months afterwards, he met with a nurse there to ask questions about his medical treatment and to talk about any feelings that arose. “I didn’t feel alone,” he says. “I felt supported and accompanied in my decision. It helped a lot to know the support was there. I felt more in control. For me, the biggest part of HIV is losing control of life. When I was told I had to start meds, I didn’t feel that sick, and so I didn’t feel in control because I wasn’t even aware of the problem. The control came back when I learned my options.”

The nurse at the clinic also offered a key piece of advice when Daniel mentioned that he wasn’t going out at night because he had to be home to take his meds. She suggested he take his meds along with him in a small mint box. It was an easy solution that allowed Daniel to keep control of who knew he was taking meds and still permitted him to keep enjoying his social life.

For his part, Bill says he received one of the most important tips about how to stick to treatment on the day he decided to start therapy. He was in the elevator leaving his clinic in Montreal when a fellow passenger imparted these words: “Even if you are just going down to the store, take a dose with you. You never know when you’ll meet friends who want to do something. At that moment, you don’t want to have to rush home to get your meds.” Since then, Bill always carries a dose of his meds with him.

More than 10 years after starting his first regimen of 3TC (Epivir), AZT and saquinavir (Invirase), Bill is still on the same combination. He’s an anomaly and he knows it. He puts it down partly to good genetics and partly to his committed adherence. Currently, his CD4+ count is between 500 and 600 and his viral load is undetectable.

Gaining control

Gaining a sense of control, like Daniel and Bill achieved with their scheduling tricks, is one of the goals of an innovative program at the Ottawa Hospital. Dr. Louise Balfour, a clinician and researcher at the hospital’s HIV clinic, has designed a program to help PHAs get ready to take treatment before they start. The program, called STAART, includes four one-on-one sessions in which a psychologist and PHA discuss a range of topics around HAART. It covers pill-taking and strategies to keep on schedule as well as broader issues such as feelings about taking meds and better ways to communicate with others, including doctors. By providing information and tools, the program aims to better prepare PHAs for adherence challenges when they arise.

The program also includes a session on dealing with stress and depression. Depression is common among PHAs, affecting an estimated 25 percent to 40 percent. And studies show a link between problems with adherence to HAART and depression. This makes sense given that many of the symptoms of depression, such as problems with concentration and memory and feelings of hopelessness (a sense of “why bother?”), could lead to difficulty with taking meds on schedule. Some of these symptoms are not what people normally think of as depression, so it’s important to talk about them with your doctor.

Researchers have come up with a long list of things that can help or hinder adherence. Aspects of the regimen itself, such as daily number of doses, are obvious. Patient attitudes also reveal things that might be expected. A 2005 Canadian study noted that the confidence PHAs have in their ability to stick with the regimen and their optimism about taking meds were key to staying adherent. But clinical data on deeper issues, values such as sense of self-worth, are missing. “I think you have to like yourself,” says Bill. “Self-respect has a lot to do with keeping up with adherence.”

Bill says he’s made taking his pills a priority. When asked about whether he has ever been in a spot where he just couldn’t take his meds, he replies, “I’ve never gone through a period where my adherence faltered. Over and above everything else going on, I knew I had to take my pills.”

ACCM’s Gillian Kolla puts it this way: “You’ve got to build a good relationship with your meds.” Like any long-term commitment, adherence to a HAART regimen involves respect, effort, negotiation and maybe a few slips along the way. But if you are prepared before starting your meds, the obstacles will seem a lot easier to navigate. Daniel and Bill are sure to agree — the payoff far outweighs the effort.

David McLay, PhD, is staff writer/editor at CATIE in Toronto.

Illustration: Beverly Deutsch