Press room ... 1997 archive

Critically Needed Information on HIV/AIDS
Treatment Adherence available in PI Perspective #22

July 10, 1997

San Francisco, CA—Reports about the successes of new treatments for HIV/AIDS have provided a welcome respite from the despair of recent years, but most recent data has begun to show increasing evidence that more and more people are beginning to fail on these therapies. Data suggest that wide-spread failure to adhere to the complex scheduling and dietary demands of combination therapy is contributing to the new wave of less-than-hopeful news. As the following article states,

“Preliminary data from one clinical trial suggest that as many as 12% of the study population missed one dose in the preceding day, 11% the day before that. At least two other recent clinical trials reported that nearly all of the people who failed to achieve and sustain a viral load below the limit of detection had significantly deviated from their prescribed treatment regimen for a month or more.”

It is imperative that HIV treatment information organizations address this issue. Despite the recent advances of therapy, current trends are no cure for AIDS. Over time, even the best treatments are likely to lose their ability to suppress viral levels below the limit of detection. How long treatments will last is closely connected to how well people adhere to the complex regimens required by the new drugs. AIDS service organizations must help people living with HIV understand the importance of adherence in maintaining the hope offered by the new drugs, and must help them develop methods to cope with the demands made by these drugs.

For over a decade Project Inform has provided insightful analysis and practical information on HIV treatment, research and national policy. The attached article is featured in the newly expanded July issue of PI Perspective (issue #22) and outlines the impediments to adherence as well as some practical tips and guidelines that have helped some Project Inform constituents. In addition to being several pages longer, the new PI Perspective takes on a new look with this issue. We urge you to reprint this article in your publication and to let your readers know about our information and how to access it - including our award-winning internet site. In addition to information about all the latest therapies under development, this issue also includes such special articles as:

The Coming Sunset on AIDS Funding Programs - a call for new thinking on AIDS appropriations;

New Federal Guidelines for the Use of Antiviral Agents - a useful summary of the new guidelines for the treatment of HIV;

HIV Side Effects - suggestions for dealing with common side effects and a chart to help identify which drugs may be contributing to side effects;

New Developments in Women and AIDS Research - the first update on women-specific issues in HIV treatment from Project Inform’s newest information and advocacy program, Project WISE.
Please contact Ben Collins at the number above if you are interested in reprinting any of these articles. On the last page of this fax, you will find information on Project Inform’s guidelines for reprinting this copyrighted material, information on how you can access electronic versions of the articles, and further information about Project Inform. We do not request or require payment, this is not an advertisement, nor is it paid for by direct or indirect pharmaceutical company support.

Maintaining Adherence to HAART
Highly active antiretroviral therapy (HAART) has brought new hope and new challenges to people living with HIV. However, if these treatments are not used properly (i.e., doses are repeatedly skipped, taken at lower than prescribed dosages, or not taken at scheduled intervals), drug resistance will almost certainly develop more rapidly and the potential benefits of combination therapy can be lost. Moreover, resistance to one therapy may also result in decreased effectiveness of other therapies of the same class (cross-resistance). This is particularly true in regard to protease inhibitors. The development of high level resistance to any one of these drugs almost certainly conveys some degree of resistance to all the other drugs of this type. Adhering to a treatment regimen is difficult under the best of circumstances. Studies have shown that even health care providers can find it difficult to take a simple course of antibiotics as directed. The new triple combinations used with HIV disease typically require that a person take a dozen or more antiviral pills per day with specific timing and dietary requirements. When a person must also use preventive or maintenance doses of drugs for opportunistic infections, the total daily pill count soars. Keeping track of one’s medication alone becomes a major activity. It’s little wonder that many people have trouble keeping up with the program.

Preliminary data from one clinical trial suggest that as many as 12% of the study population missed one dose in the preceding day, 11% the day before that. At least two other recent clinical trials reported that nearly all of the people who failed to achieve and sustain a viral load below the limit of detection had significantly deviated from their prescribed treatment regimen for a month or more. There are many possible explanations for failure to adhere to the treatment regimen. A recent study by the University of California Center for AIDS Prevention Studies (CAPS) showed that, of those people who admitted missing one or more doses:

40% said they simply forgot
37% slept through a dose
34% were away from home
27% had changed their therapy routine
22% were busy13% were sick
10% were experiencing side effects
9% were depressed.

There appears to be little debate about the fact that it is difficult to maintain perfect adherence to today’s complex treatment regimens. It is somewhat less clear what degree of non-adherence is tolerable and how quickly it contributes to drug failure. Most of all, it is not entirely clear what to do about it, though many useful strategies are evolving over time.

Initiating Therapy
Engaging in complicated courses of long-term treatment doesn’t feel natural to most people. However, this challenge is not unique to people with HIV. Millions of people have learned to cope with diseases requiring complex, long-term management, such as diabetes. Whether or not you feel you are able to commit and adhere to a treatment regimen may be one factor to consider, along with lab results and clinical condition, in determining the appropriate time to begin highly active antiretroviral therapy (HAART). Giving careful thought to what benefits you hope to get from treatment, how you will evaluate the benefit and how you might manage side effects will be helpful. Some people try a “dry run” before beginning therapy, taking empty gel caps on the prescribed schedule while sticking to the required dietary requirements.

Perhaps the first and most important aspect of adherence lies in choosing the right therapy in the first place. Drugs differ widely in:

Whether they can be taken with or without food
How many times per day they must be taken
What other drugs they can and cannot be successfully used with
Their side effects and how they make a person feel
Whether you have access to the facilities need for storage (for example, refrigeration for supplies of ritonavir [Norvir]).
Similarly, people differ widely in their personal habits and needs. A few examples:

Some people are bound to rigid schedules defined by their employment, such as hourly workers.

Some people have loose and constantly changing schedules or routinely move in and out of different time zones, such as many airline workers.

Some people are unable to work and their schedules are dictated by a seemingly endless string of medical appointments.

Some have children, elderly parents, or partners to care for as well.
Some have people around them all the time to help remind of their medication schedules, while others are alone and must rely on timers, pill boxes and other devices.

Some people suffer from wasting syndrome which makes eating difficult and critical; others have no dietary problems but don’t eat on a regular schedule.

Finally, some people have to deal with other challenging life issues such as substance abuse or homelessness.

To find a treatment regimen you can live with, it is necessary to reconcile the two sets of requirements: yours and the drug’s.

People who lead busy, but largely unstructured lives might prefer drugs that can be taken easily with or without food and thus more easily fit in with their changing daily routines. Others whose time is tightly structured by job requirements might find it easier to accept more demanding drug schedules and therefore can select a regimen purely on the basis of its expected potency. People who have trouble eating or who are struggling with weight loss might wish to avoid drugs which can’t be taken with foods. People who must take a large number of other drugs for treatment or prevention of opportunistic infections might avoid antivirals that have the highest number of drug interactions or require the greatest number of pills per day.

The goal is to select a regimen you believe you can live with, one that fits with who you are and how you live. There are, of course, no perfect choices in this regard. Some people may seek a regimen that most easily fits their lifestyle, while others may be willing to adapt their lifestyle in hopes of getting the most potent possible treatment. Also, the more HIV medications you have used previously, often the fewer choices you have about what to use next. Thus, often in more advanced disease, prior history with the drugs tends to dictate what can and can’t be done.

Maintaining Therapy
Once a regimen has been selected, sticking to it requires planning, support and commitment.

Planning
Stable access to drugs is a critical requirement for effective use. People cannot adhere to a regimen if they do not have continuous access to the drugs. While it may sound obvious, many or even most people taking HIV medications sometimes find themselves running short of one or another treatment. This is almost always a consequence of poor planning. Skipping doses when you run out of a drug temporarily is still skipping doses, with all the consequences. Thus, it is best to try to plan to never have less than a week’s supply of your entire medication needs on hand. Remember also that some drugs require much different storage than others, so part of your planning must address the storage requirements. Once storage is addressed, it is often helpful to put aside an entire week’s supply the first time the drugs are delivered, and then use only the remaining supply. This will also create an “emergency stash” should unforeseen circumstances cause your basic supply to run short. The “stash” should be rotated or replaced once a month to keep it fresh.

Keeping a steady supply of your prescriptions requires close coordination with your doctor and your pharmacist. When using sources like the AIDS Drug Assistance Programs or patient assistance programs sponsored by pharmaceutical companies, which are potential sources of drug access, more of the burden falls on you to make sure you order supplies as the program requires. But the main point is always to stay at least a week ahead of your needs. Your care provider should work closely with you to ensure access.

People with varying lifestyles may differ in their ability to adhere to a treatment regimen. People dealing with major life problems such as active drug use or homelessness face the most difficult challenges adhering to a treatment regimen. But that doesn’t mean that adherence is impossible. Studies have shown that people with depression are also more likely to have difficulty taking their treatments consistently. If you suffer from depression and are considering treatment, consult a mental health professional as well as your regular provider. Outside of depression, there are very few reliable predictors of non-adherence. In reality, only you can make the decision as to whether you are ready and committed enough to maintain a steady course of treatment. If you are not ready or in a position to make a serious attempt at adherence, you might be better off to delay treatment. This option doesn’t jeopardize your ability to use treatment effectively some time later in the future. In contrast, the misuse of treatment, through inconsistency or poor adherence, can indeed jeopardize future options by encouraging development of drug resistance that affects entire classes of anti-HIV therapy.

Support
Establishing a good working relationship with your provider is critical for maintaining adherence to a treatment regimen. A provider should be knowledgeable in the current standards of care for treating HIV and should be willing to spend time to thoroughly explain the benefits and challenges of treatment.

After the decision to start treatment has been made, it is important to clarify your treatment regimen with your physician. Knowing what medications you are taking and why will help to better understand the importance of adherence. One survey indicated that the vast majority of people were unclear of their treatment regimen only ten minutes after consulting with their physician. Some people understood the dosage but were confused about dietary restrictions. Others were unclear on the correct dosage or the timing of the doses. Since dietary adjustment can be a difficult at first, it is important to know what and when you can and cannot eat. Just as important, try to understand exactly what is meant by the dietary requirements. For example, many people interpret the requirements for indinavir (Crixivan) as saying that the drug should not be taken with food, which can be difficult for many people. The actual dietary requirement is that it shouldn’t be taken with fatty foods. Light snacks and non-fat foods can be taken with the drug without concern. . Similarly, the requirements for nelfinavir (Viracept) are often interpreted as meaning that it must be taken with food, when in fact the label says only that it can be taken with food. In some cases, there is a genuine medical need to take a drug with or without food, while in other cases, such as the use of ritonavir (Norvir), use with foods is recommended only to minimize side effects or unpleasant aftertaste.

A useful technique for understanding a treatment regimen is writing down instructions and repeating them back to the care provider, then checking them again with a pharmacist when you pick up or order the drugs. Use the team approach; your physician, nurse, pharmacist and other health care providers can all be helpful with initiating and supporting effective therapy. Researchers CAPS have noted that people who actively foster a friendly and supportive relationship with medical office staff get better service from their providers. Bringing another person (family member or friend) to appointments ensures that there are two people to ask questions and get information.

Ask the doctor to be clear about potential side effects and how they may be managed. Being mentally prepared for possible side effects can make them easier to manage if they occur. Make an agreement with your care provider as to what the process will be if you experience a difficult side effect. Knowing that you will have timely contact with a provider may provide reassurance that side effects will be managed efficiently. It is also important to find out from your physician what to do if you miss a dose. If you do miss a dose, find out if you should make it up a or simply take the next one. Also, note the missed dose and the reason for missing. There may be a strategy you can employ to avoid missing future doses. If you are not able to take all the drugs in your combination, don’t take a partial dose. Contact your care provider immediately. If necessary, stop all of the drugs in your combination therapy until you are able to take a complete dose again.

Commitment
At the initiation of therapy, most people question what “adherence” means. It is important to keep an adequate level of drug in your blood stream 24 hours a day in order to prevent the development of resistance. Each time a dose is missed, the blood level of the antiviral drugs falls below the minimal necessary amount for several hours, creating a temporary opportunity for the selection and growth of drug-resistant strains of virus. There are no data telling us exactly when resistance to drugs begins but there is plenty of evidence that people who are adherent to their treatment regimens have a better and more sustained antiviral response. While no single episode of a skipped or late dose is likely, by itself, to trigger resistance, the more often such episodes occur, the more likely resistance becomes.

Strategies for Adherence:
Some of the following strategies and tools have worked for many people taking triple combination therapy:

Integrating your treatment regimen into your daily routines. Most people find it easier to fit their medications into their lives, rather than scheduling their lives around their medication. Use a daily activity, one that you do every day without fail, to prompt you to take medications. Take your medications before the activity; it’s easier to remember.

Counting out all your medications in daily doses for a week at a time. Use a pill box or a nail organizer from a hardware store to hold each dose. Setting up the weekly pillbox must become a routine weekend duty. Medications can also be divided daily by dose and put in separate canisters (some people use film canisters) marked with the dosage times. Some people put each canister near the place they will take a dose. For example, put the morning dose by the coffee pot, evening by the television set. This is more difficult with drugs that require refrigeration.

Keeping a checklist for doses taken with a space to note how you are feeling.

Using an electronic pill box or beeping alarm to remind you when to take medications. The downside of these mechanisms is that the currently available electronic pill boxes are too small and the alarms may be too obvious.

Using a daily planner, especially at the start of a new treatment regimen. Inserting medication requirements in a planner, as if they were appointments, can be a useful reminder for many people. Still others use hand-held computers and inexpensive electronic organizers with scheduling functions to remind themselves of their daily medication needs. Electronic devices of this type can be purchased for less than $50 dollars.

Evaluating your treatment regimen about two weeks after you start. It may take a few weeks of experimenting to figure out how to best schedule both your medications and other events in your life. For this reason it may be useful to start a ‘dry run’ of therapy, allowing time to adjust routines prior to actually taking the drugs.

Planning ahead for weekends and vacations. People often miss doses when they are away from home. For most people, weekends are different from their normal weekday routine so it is important to plan ahead. Take into account the changed environment. Will you feel comfortable with your normal routine or will you need other strategies?

Keeping all your medications with you when traveling. Baggage containing medication can be lost or delayed.

Planning ahead for privacy if you need to hide the fact that you are taking medication. If you are not able to take your medication openly, try to find at least one person with a similar problem with whom you can discuss strategy. Some examples might be adjusting your lunch or break schedule to ensure privacy or keeping water in your bedroom at all times.

Keeping a diary—include whatever is important to you: when you took treatment, reason for missed dose, how you feel, etc. Keeping a record like this serves as a reminder of how well, or poorly, you are doing with adherence.

Using your support network to remind you of your medication requirements. Some people select a “treatment buddy” who can make daily reminder phone calls.

Setting up a support network for your emotional needs as well. It’s difficult to take treatment and also deal with daily stress, whether it be taking care of children, working or dealing with illness.

These strategies may not work for all individuals. Because of cultural, gender and socio-economic differences, some suggestions are more appropriate for some people than others. Different issues are more important in some settings than others. For example, in the Latino community, many individuals reported that people they knew might not be able to reveal their HIV status or their use of medications. This places much greater emphasis on planning ahead for moments of privacy each day. For people struggling with lack of housing, active drug use or untreated mental health conditions, the strategies for successful treatment will often go beyond what we cover here. Still, even under the most challenging situations, people have daily routines which can be used as triggers for the use of medications.

Adherence strategies can and must vary from person to person and group to group. However the most effective method of ensuring success is motivation and commitment to a treatment regimen, along with the recognition that it is possible to accommodate the need for long-term treatment. It may take several attempts before you find the approach that works best for you, but people with other life-threatening chronic illnesses have long demonstrated that it can be done. As an elderly woman with diabetes said at a recent Project Inform Town Meeting, “if you want to live, you’ll find a way to do it.”

Commentary
Perhaps the greatest way in which adherence to HIV treatments differs from adherence in other chronic illnesses is the lack of immediate symptoms or consequences when adherence fails. In diabetes, for example, failure to adhere can quickly result in insulin shock or even death. In HIV disease, the effects of non-adherence are slow to appear, but nonetheless deadly. This lack of a rapid feedback or response places more of the burden for adherence on the intellect and a bit less on the immediate reaction of the body. A person with HIV infection must take a long-term view in order to have a long-term future.

Adherence is also a challenge to the many of the support systems for people with HIV. Managed care and other economic changes in the medical field have left providers with less time to spend educating patients. Moreover, most health care providers have little or no training in the self-adherence tools that might help people who are undertaking a new treatment regimen. Training will be needed both in HIV treatments and tools of self-compliance. Some pharmaceutical companies already offer “adherence training” programs which have been developed for other illnesses. They are just now beginning to pilot test their use in HIV disease.

There are few effective structures in the HIV care and service industry to support people taking treatment effectively, such as treatment support groups and treatment-knowledgeable case managers. Many working in the HIV service field have been operating from a model of disability and death. The transition to supporting people who are living longer with complex treatments and social needs will require planning and shifts, not only in programs, but in paradigms.

The best long-term solutions must ultimately go beyond helping the individual adhere to the schedules demanded by the drugs. Instead, they must begin to focus on making better therapies and longer-lasting formulations that are easier to use, more easily absorbed, have fewer side effects and drug interactions, and maintain more consistent drug levels in blood. This work is already well underway with studies beginning this month for treatments which may require only once per day dosing. The final solution, of course, is an outright cure to the disease, one which not only results in eradication of HIV and immune restoration, but no further need for medication. The prospects for this kind of solution are, unfortunately, less certain.