Practice does make perfect, as anyone who has every learned to play a musical instrument, or volleyed with a tennis partner, or baked a batch of chocolate-chip cookies knows full well. We practice push-ups, parallel parking, public speaking, and the pronunciation of foreign words. When I was in grammar school, we practiced penmanship, day in and day out. When my children were the same age, they practiced phonics. So why don't people with HIV get to practice taking their antiretroviral medications before they actually begin therapy?

This concept makes such good sense that one wonders why someone didn't think to ask that question a long time ago. We all know that people with HIV find it hard to comply with the rigid routine of multidrug antiretroviral therapy, especially at first. We also know that close adherence to one's daily dosing regimen is essential, both to suppress viral replication and to prevent the emergence of drug-resistant viral strains. Finally, we know that time is on our side when we initiate -- or switch -- antiretroviral therapies. Except in cases of new HIV infection, where immediate treatment may blunt the impact of HIV on the immune system, it is never necessary to rush an individual into therapy.

In short, there is ample time for people with HIV to practice taking their anti-HIV medications before they actually begin antiretroviral therapy -- and there is ample reason to think that these individuals will profit from such an exercise.

Every treatment-experienced patient, and every experienced treater of HIV infection, knows that it is hard for even the most motivated individuals to stick to their daily dosing schedules -- and we all know that failure to stick to one's schedule can have serious consequences (see "Drug Resistance: What It Is, How It Develops, and What You Can Do to Prevent It," the pull out and save section of the June 1998 issue of AIDS Care). So why is it routine practice to initiate combination antiretroviral therapy without first offering these patients a risk-free dry run, to see how well they adhere to their assigned regimen?

The benefits of such a test run are obvious. The patient gets to practice taking his or her allotment of pills, day in and day out, for a period of at least two weeks -- without running the risk that poor adherence will promote the development of drug resistance. The care provider gets to assess the patient's ability to adhere to his or her assigned regimen -- and can pinpoint the dosing times that present the greatest compliance problems. And, perhaps most important of all, people with HIV get to undertake this trial in an atmosphere unburdened by the pressure, uncertainty, and anxiety that so often accompany the initiation of combination antiretroviral therapy.

The problem is, of course, that there is no such thing as a risk-free dry run. Or rather there wasn't, until my colleague Dr. Margaret Chesney helped me develop a safe, simple, and sensible way to accustom yourself to the dosing demands of combination antiretroviral therapy -- before you take a single pill. This practice regimen involves jelly beans. Now, don't laugh. We had good reasons for choosing jelly beans: they are universally available, they are roughly the same shape as many of the capsules that comprise a multidrug antiretroviral regimen, and most people like them.

Okay, not everyone likes all the flavors -- opinions are particularly divided when it comes to the licorice flavor -- but this can actually be seen as an advantage. As anyone who has been on combination therapy can tell you, some anti-HIV medications leave an unpleasant aftertaste in your mouth. You will need to adjust to this reality if you are assigned one of those medications, and a good way to begin making that adjustment is by deliberately choosing a jelly bean flavor that you don't like as a stand-in for one of your assigned drugs.

The idea behind this two-week dry-run is to let you settle into your daily dosing schedule in a low-key, low-pressure, low-risk fashion. The jelly bean exercise is a game, but it is a game with a serious purpose -- and it will be effective as a teaching tool only if you take it seriously. We hope you will do just that, because the lesson that this exercise has to teach you is a fundamental one: Learn to take your stand-in medications at the right times and in the right combinations and you will find it much easier to take your actual medications at the right times and in the right combinations.

Practice makes perfect

The "treatment plan" in this special pull out and save section outlines a typical drug regimen for an individual who is beginning anti-HIV therapy (or one who is being switched from a less potent regimen, or from a regimen that is no longer providing near-complete suppression of viral replication). As you can see, this treatment regimen begins with one of the most widely prescribed three-drug antiretroviral combinations: AZT, 3TC, and indinavir (or Retrovir®, Epivir®, and Crixivan®, to use their brand names). The first two drugs are nucleoside analogs, members of the oldest class of anti-HIV medications; the third is a powerful member of the class of antiretroviral drugs known as protease inhibitors. In combination, these three medications can suppress viral replication below the level of detection of standard commercial assays.

When AZT and 3TC are taken together, the latter drug effectively reverses much of the resistance that develops to the former. For this reason they are often paired in prescriptions. Indeed, they are now available as a two-in-one tablet, which goes by the trade name of Combivir®. If your care provider includes AZT and 3TC in your anti-HIV regimen, you will take these drugs, separately or as a single tablet, twice a day. Normally, people choose to take these nucleoside analogs with meals. Crixivan, on the other hand, must be taken every eight hours, must be taken on an empty stomach, and must be taken with two tall glasses of water (see the "Special Instructions").

 

The "treatment plan" also includes three drugs that are commonly taken by people with HIV to prevent what are known as AIDS-related infections (because they occur in those individuals whose immune systems have been seriously eroded by HIV). These drugs include bactrim (Septra®) to prevent the most common of all AIDS-related infections, Pneumocystis carinii pneumonia; azithromycin (Zithromax®) to prevent Mycobacterium avium complex, another serious infection to which people with profoundly compromised immune systems are prey; and fluconazole (Diflucan®) to prevent candidiasis, commonly known as thrush when it occurs in the throat and as yeast infection when it occurs in the vagina.

Your own regimen may exactly duplicate the sample treatment plan that we have provided... or it may include only one or two of these drugs. With so many treatment options now available to people with HIV, the possible combinations are almost impossible to calculate, especially when one includes the four- and five-drug antiretroviral regimens now being tested in clinical trials. Depending on your own clinical status, as measured by your CD4 count and viral load, you may be assigned fewer drugs as prophylaxis -- or more.

In any case you will want to choose a jelly bean color to represent each of your assigned drugs. The choice is up to you, but once you have made your choice you should stick to it throughout your two weeks on "jelly bean therapy." The idea is that you treat the jelly beans exactly as you would treat actual anti-HIV medications, taking them in the prescribed number and at the prescribed times. It may seem odd, particularly at first, to be consuming a handful of jelly beans with breakfast, but then taking a handful of assorted pills at breakfast is also going to seem odd at first, so the sooner you adjust to the oddity, the better.

You can cheat, of course. You can dump your black jelly beans in the wastebasket, or feed them to the dog. You can gobble up your day's allotment of jelly beans while you watch the late-evening news instead of spacing them out at the appropriate intervals throughout the day. And you can tell your care provider that you took all of your "pills" exactly as you were supposed to. But the only person you will be cheating is yourself. This is your opportunity to accommodate yourself to the rigorous demands of combination antiretroviral therapy, and you owe it to yourself to use this opportunity to best advantage. Use the "daily record" on page 3 to record each dose you take, noting any variances from your assigned dosing schedule. This will help you to identify the doses you are most likely to forget to take on time, or to forget to take at all. Once you know where the problems lie, you will be able to develop strategies that will help you remember to take those doses at the proper time.

"Mastering Combination Therapy," which appears below, can help you develop those strategies. The prudent, practical, easy-to-follow advice in that section was developed for us by men and women who are veterans of the war against HIV. Some of them have been on one form of antiretroviral therapy or another since AZT first became available a decade ago. They are pro pill-takers, and their cumulative wisdom will help you find ways to remember to take your own medications exactly as they were prescribed. :

Mastering Combination Therapy

The new multidrug regimens that work so effectively against HIV oblige you to take your medications on a fixed schedule throughout the day. Here's how to integrate all that pill-taking into your daily routine

No one said it would be easy. But even so you may not have been prepared for just how complicated combination therapy can be. Suddenly you have to get up at the same time every day. And eat meals at the same time every day. And go without food for specific periods. And drink a specified amount of liquid over the course of the day. Every day, without fail.
At first, these regulations and restrictions may seem overwhelming. All you are doing, it seems, is taking pills. Or worrying about when you need to take the next pills. Or fretting about whether you have done yourself some unspecified harm by forgetting to take some of your many medications at the specified time.

For your peace of mind -- and to maximize the effectiveness of your antiretroviral "cocktail" -- you need to integrate all this pill-taking into your daily routine. Do that, and you can master the complexity of combination therapy, so that it no longer dominates your day.

The following suggestions come from old pros at pill-taking -- some of whom have been on antiretroviral therapy since AZT was introduced more than a decade ago.

 

• Choose a regular time -- say, Sunday night, right after a TV program you always watch -- to count out all of your pills for the following week. Do this in a well-lit place where there are minimal distractions (such as loud music or household pets), and take your time. Count carefully -- out loud, if that helps. This is especially important if you have been instructed to increase (or decrease) your doses at intervals of several days.

• Put each day's morning, noon, early-evening, and late-night doses into separate compartments in one of those see-through plastic boxes that are designed to hold an entire week's supply of pills. Walgreen's has a version with four compartments for each day of the week and a snap-shut lid.

• Get yourself several small containers. (Empty film containers work well for this purpose. Color-code them with tape or marking pens for easy identification.) Before you go to bed each night, take the next day's doses out of your plastic pill tray and put them where you are sure to see them at the appropriate times the following day. Set the morning doses next to the coffee-maker; pack the noon doses in your attaché case or gym bag; and place the late-night doses by your toothbrush.

• Buy a watch with a silent alarm -- one that hums on your wrist but makes no noise -- or get yourself a vibrating alarm that you can carry in your pocket or wear in your waistband. Set these timers -- or a clock-radio -- to go off at the times during the day when you are most likely to forget to take your medications.

• Enlist someone you live with -- a spouse or partner, a family member or roommate -- to help you remember to take your pills at the prescribed times. If you live alone, get a good friend to call you at set intervals during the day, just until you get used to your new dosing routine. Or find a friend who is on a similar antiretroviral regimen, so that you can help one another to remember your shared daily schedule.

• Don't panic if you miss a dose. Everyone does. You're not a robot, you're human... and humans slip up. If you do miss a scheduled dose, read the instructions you got with your pills. They will tell you if you should make up the missed dose or wait until it is time to take the next dose.

• Make two clock faces like the ones on pages 6-7. Label one daytime and one evening; mark your daily dosing schedule in large, legible letters on each clock; and hang these reminders in places where you are sure to see them. For work and travel, make wallet-size versions of both clock faces and carry them with you wherever you go.

• Do the best you can, and stick with it. Like everything else, this gets easier with practice.

Helen M. Miramontes, M.S.N., R.N., is Deputy Director at The International Center for HIV/AIDS Research and Clinical Training in Nursing and a member of the President's AIDS Advisory Council