Being Alive; June, 1998
Walt Senterfitt

When asked what was the "number one reason" why adherence to the drug therapy was so difficult, 22% cited the requirement of many drugs to be taken with or without food. Fourteen percent cited the complexity of their pill-taking regimens, and 13% said they were bothered by the side effects. Nineteen percent listed a wide variety of other reasons, including concerns about privacy, the taste of the drugs, their costs and difficulty in swallowing pills.

The deviations from prescribed drug regimens in this group were not limited to the occasional missed dose. More than half the 43% who said they had not been able to keep to the schedule also said they had taken complete "drug holidays" of a few days to a few weeks. The average drug holiday was two weeks, clearly long enough to allow suppressed hiv to bounce back and repopulate one's immune system and even for symptoms to recur.

How Much Does It Matter Anyway?

This is the big question and one for which we don't have a precise answer. In fairness to scientists, it is not an easy one to study, especially for regimens as complex as those for hiv. Many factors influence one's success in fending off the encroachment of aids symptoms in addition to medications. And many other factors influence the absorption and effectiveness of the drugs beyond the basics of whether or not you swallow the pills.

Still, even if we are not able to say how much it matters, we do know that it does matter. Empirical studies show that in general those who are comparatively more adherent are less likely to have symptoms, progress to aids or lose T-cells in any given period.

The biologic logic underlying these findings is also pretty clear. Even the best current HAART does not eliminate hiv, but rather suppresses its replication or growth. When drug regimens are stopped, even for as short a period as a day and certainly within several days or a very few weeks for almost everyone, the hiv reserves take advantage of the "coast being clear" and start repopulating the immune system.

The natural mutation of hiv within the body creates different sub-types of hiv in one's reservoir or "archive," unless you were lucky enough to start effective therapy very early in your infection. So when drugs are stopped, the hiv that springs back may either be the original type that the drugs can handle (fine and dandy) but then again it could be a resistant mutant that the former drug regimen cannot control.

This is why drug holidays and only semi-regular adherence can cause failure of drug regimens more quickly, by allowing resistant mutant virus to emerge. The potential, and nasty, effect can be even greater than in one individual's life, if s/he transmits drug resistant virus to someone else and therefore out into the community "hiv gene pool."

However, we need to know more about where the thresholds lie for most people, and how they vary from person to person, so we can really help each other know the difference between a particular level of non-adherence which is risky vs. one being downright dangerous! Until we do have such information, it is only smart (however annoying) to err on the side of excess caution and strictness.

Does Any Group Have More Trouble Than Other Groups?

In general, no. Demographic characteristics such as age, race, gender, ethnicity, social class, sexual orientation and educational level have not been found to be associated with adherence either in the general research literature or in the previous studies of AZT. Studies of combination therapy are just beginning to hit the literature, but there is no reason to expect them to be any different. Studies in homeless populations in San Francisco and New York City have shown that with adequate instruction, discussion, planning and support, adherence rates are comparable to or better than in privately insured groups of middle class men.

Beliefs of providers, case managers and community aids organizations may be at variance with this fact, however. It is naturally important to all of us that we not allow prejudice and incorrect assumptions to affect who gets the chance to use these drugs and who doesn't. So far, evidence from the epicenter cities like New York and Los Angeles seems to indicate that providers are in general bending over backwards not to exclude groups from being prescribed HAART regimens. Eighty-four percent of physicians interviewed in the Johns Hopkins study mentioned above acknowledged that they do, however, make individual judgments, either alone or in consultation with their patients, about whether or not someone is likely to adhere and thus whether or not an individual should be prescribed protease-inhibitor combination therapy. This realm of individual judgment is obviously capable of reflecting either sound practice or questionable bias.

Who Is Likely to Have More or Less Trouble?

There clearly are individual differences in commitment and ability to adhere to these complex regimens. A number of characteristics are associated with adherence and a number of barriers to adherence have been identified. (None of them are magical or mysterious!)

Patients' beliefs in the need for treatment, understanding of the purpose and nature of the drugs, expectations that the drugs are likely to be helpful and supportive friends and community norms and values have all been found to be associated with greater adherence. Trust in one's physician and confidence in one's own ability to follow guidelines are also predictors of adherence. Conversely, poor understanding of the medications, general suspicion of medications or of the medical care system and weak social support are all associated with refusal of treatment, stopping medications or taking the regimen lightly.

Active substance use is likely to interfere with adherence to combination therapy, but does not have to be an absolute reason to not undertake it. Studies and pilot projects have shown that careful planning between the provider and the patient, and use of community services, can promote successful use of combination therapy. For many hiv+ active users, there is a strong motivation to succeed particularly when they have seen friends die quickly without HAART and live better with it. The relatively high street price of black-market protease inhibitors among New York City drug injectors is testament to community norms about the medications' value!

Dementia and other forms of cognitive impairment and severe and persistent mental illness are all likely to lead to major adherence problems. People may have trouble sorting and keeping track of their pills even with the best of intentions. Even mild psychiatric conditions such as depressed mood can be associated with non-adherence either through a sense of despair and hopelessness or through impaired concentration.

The combination of active substance use and active mental illness is an especially difficult context for successful adherence, coming as it does typically with homelessness or unstable housing.

As well as a social context, there are biologic limitations to the ability of many to adhere. Many of us cannot tolerate or absorb these medications, have life-threatening toxic effects or cannot manage taking in enough food and sustenance and still meet the medication requirements. A key area of change that must occur is for scientists and drug companies to develop more tolerable drugs and regimens.

What Helps?

There are a number of ideas and programs out in the community intended to help promote adherence. Unfortunately, we know very little about which of them work best, and for whom. There has been little behavioral research thus far on the effectiveness of adherence interventions.

However, some things are just plain common sense, and others clearly offer enough promise to be considered.

Take your time. To start with, everyone starting out on combination therapy and every provider considering prescribing it should take time to learn about the medications' actions and purposes, requirements and how taking them will fit a person's particular life circumstances. There needs to be a variety of means to impart such information, from extended conversations with providers, to written and audiovisual material to peer support groups and treatment advocates. Consciously choosing a good time to start a new regimen is important. A student, for instance, will probably not want to start combination therapy just as final exams begin, because almost any regimen carries the risk of temporary side effects the first couple of weeks.

Assess one's daily schedule. Individuals and nurses have found that a careful and honest day-by-day and hour-by-hour assessment of a person's ordinary life is essential to integrating successful pill-taking, and perhaps choice of the best regimen. For instance, someone working in an environment where people do not know his or her hiv status may find it difficult to regulate complicated mealtime restrictions.

Practice, even before you begin. There is no reason to expect any of us to know how to manage these medications from the get go. Success requires a complex package of information, skill and reorganization of our lives. Like any complex task, there is a learning curve and usually a period of making frequent mistakes. Some physicians therefore initially prescribe regimens that are more "forgiving" of non-adherence than those containing protease inhibitors. Another idea is to try a week of taking "dummy pills," like different colored jelly beans or M&Ms, and noting the particularly difficult times and situations during a week in one's life.

Make a plan. With what is learned from assessment and practice, make a written (or pictorial or verbal) plan. Some people find a detailed plan works best, with cues to different events in daily life schedules. Others find just a simple and general one enough.

Look into mechanical aids. There are pillboxes, timers, beeper systems, refrigerator notes and a host of other little devices that can help remind a person of the time to take pills, or to stop or start eating in preparation.

"Boot camp." Some have proposed, and are planning, residential programs for a few weeks at the start of combination therapy for those whose success will depend on making and sustaining some significant changes in their lifestyles and habits. Maybe it will work!

Social help. Support groups of people who are all dealing with new combination therapy regimens can help. Buddy systems are being set up, especially for the first weeks of therapy. Sometimes a hotline at one's provider, or a proactive calling service by provider staff, can help a lot. Even an initial home visit or two by an experienced nurse or buddy can help someone figure out how best to integrate medication requirements into daily life and varying lifestyles. Sharing tips in this Newsletter is encouraged!

Is It All Worth It?

All things considered, I think most people who are taking HAART would say yes. As W.C. Fields' tombstone reportedly says, despite a lifetime of jokes trashing his native city, "All things considered, I'd rather be in Philadelphia."

I think that we as a community, of PWAs and hiv positives and health care providers and aids organizations, should clearly recognize the challenge we are up against in adherence. Rather than an Achilles heel, it is better to think of it as a complex task that we must help everyone master. Perhaps an analogy is learning to drive an automobile safely in a city such as Los Angeles. This is certainly a complex task requiring many component skills, a knowledge base and practice. Yet almost everyone learns to do it successfully (or else!).

We should certainly push researchers and drug companies to make better drugs that are easier to take. Treatment activism is still very important. Meanwhile, we have each other.

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ÆGIS is made possible through unrestricted grants from Roxane Laboratories, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 1998. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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