Thinking about adherence before starting treatment

Few people find themselves in a position where starting HIV treatment is an emergency, and so doctors advise that thorough planning and preparation are important steps in maximising the effectiveness of a new HIV treatment regimen. Ideally, this should begin well in advance of treatment being prescribed, and needs to consider the wide range of factors which might act as enablers or barriers to high adherence in your case.

Though there is much that your health care team should offer to help you on your way, it's important to remember that in most cases, the primary responsibility for managing adherence will rest with the patient taking the medication. This means that you must feel ready to start and committed to following the regimen as prescribed, being aware that you are likely to be taking your treatment for the long-term. If anything causes you to feel unsure that you can manage this, it's important that you seek support promptly from a member of your health care team.

Make sure the drug schedule fits your life

If you find that you are missing your doses during the day discuss this with your doctor as it may be possible to tailor your schedule to make it easier to remember, or to change the medication. Many anti-HIV drugs can now be taken once or twice daily and there are options which reduce the burden of food restrictions.

HAART regimens vary in the number of doses required per day, whether they should be taken with food or without, the number of pills per dose, the size and shape of the pills, and so on. These factors may be more or less important to different individuals, but in general, people adhere better to regimens dosed once or twice a day than those dosed more frequently.

Recent research sponsored by GlaxoSmithKline (who make AZT, 3TC and abacavir) reported that when people with HIV were asked to describe their 'ideal' HAART regimen, most wanted to take just one or two small pills dosed once a day, without food restrictions, and with a low risk of side-effects (Stone 2004). Evidence from several other studies also shows that people adhere better to regimens that contain fewer pills and that are dosed once daily (Knobel 2004; La Paz 2004).

Nevertheless, there seems little sense in making adherence more difficult than it needs to be. HAART regimens are selected on an individual basis by weighing up several key factors: potency, the risk of side-effects, likely viral resistance patterns, the need to avoid harmful drug interactions, and of course, likely adherence levels.

Divide up your doses at the beginning of the week

Dividing all the drugs up into daily doses and storing them together may help you to see when you have missed a dose, and will also avoid the annoyance of having to open lots of pill bottles and carry them around every day.

Devices for storing drugs

There are devices such as Medidose, a plastic box with several compartments for each day which can be pre-loaded with tablets and capsules for up to a week in advance by the patient or a helper which make taking a multi-drug regimen much easier although, they can be a bit time-consuming to fill. It is possible to obtain them from hospital pharmacy departments or on special order from retail pharmacies.

Some pill-boxes are available which sound an alarm when it is time to take the next dose (`beepers'). These provide a convenient way to carry medication as well as reminding you of the need to take the medicine at the appropriate time. They tend to be advertised in publications targeted at the elderly, and are rarely to be found in pharmacies or chemists in the UK.

You can also get little boxes from hardware/DIY stores which are designed for storing nails, screws or other small items. They have lots of subdivisions. You may find that one of these is a cheap alternative. Film canisters may also be useful.

However, it's important to be aware that some drugs have their own storage requirements. For example, indinavir needs to be stored with the special device called a dessicant that is supplied with each pill bottle. The dessicant protects the pills from moisture in the air; if indinavir capsules get at all damp the drug will cease to work. The capsules also appear to react with some other anti-HIV drugs when they are stored together, so for the moment the manufacturer recommends that indinavir tablets shouldn't be stored in the same container as other drugs.

If you're unsure about the best way to store your medication, speak to your HIV pharmacist who will be able to advise you.

Leave it where you can see it

Keeping your pills where you can see them may be a good visual prompt, and some people may even divide the doses up and put them in different places according to where they are likely to be when that dose needs to be taken - for instance, beside the bed, beside the kettle or beside the television. Of course, some people do not want the continual reminder that they are HIV-positive. For others, leaving tablets about the house may advertise the fact that they are HIV-positive, and may be unacceptable.

Keeping your medication confidential

Taking combination therapy can present problems for people who don't want to reveal their HIV status to others. For example, if you have to take a dose while at work, can you go to the toilet and take your pills there, immediately after eating?

Do you have a place at work where you can store pills without them being discovered? For example, do you have a lockable desk drawer?

Regimens which are dosed less frequently - say once or twice a day - may be helpful to people who do not want to take treatment in their workplace, for example.

If you don't want other members of your family to see your medication, you may need to store it in new bottles which don't bear the name of the drug. Do take care with this as it's important that your treatment is not mistakenly consumed by others, and that you don't become confused about how your drugs should be taken.

If you are visiting family or friends for a few days, it is worth noting that drugs which need to be kept in the fridge do not need to be kept refrigerated every moment of the day. In fact, in temperatures under 25 degrees C, ritonavir can be kept out of the fridge for several days but it does need to kept cool in hot weather.

If you share a house with people and don't want to take medication in front of them or visitors, it may help always to keep a bottle of water beside your bed so that you can take your pills in privacy. Alternatively, if it's medication that you have to take after food, tie it in with visiting the bathroom to brush your teeth.

Practise beforehand

It may help to practise your particular dosing schedule before you do it for real, to give you confidence that you will be able to stick with it. Some people have suggested substituting sweets for drugs, but if you don't feel this seems medicinal enough, or you don't eat sweets, try vitamin tablets. Try and find some cheap, low dose vitamins, and buy one sort for each drug in your chosen combination. Then try and follow the dosing schedule. For example, if you've got to take ddI, find a tablet which you have to suck or dissolve, such as vitamin C, and take it with the same dietary restrictions as ddI.

Side effects and adherence

Intense side effects can occur in the first few months of treatment when especially high levels of the drug are present in your bloodstream. After a few weeks the peaks and troughs in blood levels of the new drug become less pronounced, and side effects wear off. This is why some doses of some treatments, such as ritonavir and nevirapine, are gradually increased over several days or weeks.

If you have decided that it is worth taking a particular treatment, this is an important reason to persevere for a few weeks (as long as your doctor feels that this is safe) even if at first the side-effects seem unacceptable. During this period you may need to take other treatments to deal with the side effects, such as anti-nausea or anti-diarrhoea medicines.

Before you start any treatment, it's important that you understand what to expect in terms of side-effects, and how to respond should they occur. You should know who to speak to at your clinic if you are concerned, and in some cases, which symptoms need to be reported immediately. These issues may also influence the timing of starting a new treatment. It may be helpful to take time off work, and to know that family and friends can be called upon to support you if you have difficulty with childcare, for example.

Experiencing side-effects is one of the most common reasons for low adherence. Nausea, vomiting, diarrhoea, fatigue can all act as practical barriers to taking medicine. However, your emotional response to experiencing side-effects may be just as important. If you come to believe that your medicine is doing you more harm than good, you may lose your motivation to take your treatment regularly. If this is how you feel, do speak to a member of your health care team, who may be able to reassure you or discuss options for managing side-effects or changing treatment.

What support do you want from others?

This will depend on how much you want to tell others about your HIV status and your treatment, and how often you can stand other people reminding you to take your medication! It may be helpful for friends who know you are HIV-positive to be told what kind of reminders about taking medication you will welcome, and how long for. It may also be worth reminding them that when you start treatment you may have side effects for a while, and that you may not be up to participating in normal activities.

Keep some medication at work or other places you spend significant time

Some people find that their lifestyle is not regular. They don't get up in one place, go to work and then come home again every night. They may spend part of the week at a partner's home, or go out after work, or work shifts, or stay out all night. In these circumstances it's important to have back-up medication in different places.

Weekends or holidays may be difficult

Many people report that it's difficult to stick to weekday drug schedules at the weekend. For example, if you're used to taking your first dose of the day at 8 a.m. you may not want to get up at this time on a Sunday. You may not always eat at the same times at the weekend, and you might go to bed much later. You may find that practicing your weekend medication schedule is far more important than practicing the weekday schedule before you start on combination therapy. Practicing for four to six weekends may allow you to identify the problem factors for taking medication successfully in the ways you spend your weekend, and may lead you to choose a different combination.

Which other drugs are you taking?

Your doctor and HIV pharmacist will be able to provide information on potential interactions between your HIV medicine and any other treatments you may be taking. It's important to be frank with them if they are to help you.

Drug and alcohol use could also present problems if you end up missing doses whilst 'under the influence'. A significant proportion of gay men taking protease inhibitors at a London clinic reported missing doses because of recreational drug use. At least half of them were deliberately missing doses because they were unsure about interactions with recreational drugs.

When travelling

If travelling by air, do not put medication in luggage which goes in the hold. This is the luggage which can most easily go astray or get lost. Make sure your medication is in your hand luggage.

Time zones can also be a problem. If you are in a different time zone for a day or two (for example two to three hours ahead of your normal time), it may be easiest to stick to the normal regimen. Longer trips may require more consideration. Again, your health care team can help you work out a plan before you travel.

Directly observed therapy

Directly observed therapy (DOT) involves a health care worker giving a patient his or her medication every day. DOT was originally used to administer treatments for tuberculosis but is increasingly being used to administer antiretroviral therapy to marginalised HIV-infected populations. Many heroin substitution programs also directly observe the administration of methadone on a daily basis.

Typically, marginalised populations are defined as prisoners, injecting drug users, children, racial and ethnic minorities, and people in resource-poor settings.

Unlike the above strategies which seek to empower HIV-infected people and to integrate HIV treatments into the daily routines of infected people, DOT removes the power and autonomy of the infected person. DOT strategies are often criticised for this reason.

Nevertheless, DOT may be convenient for people already receiving methadone or other DOT medication. It may also be suitable for homeless people who have no place to store drugs safely. In resource-poor settings, DOT can ensure an uninterrupted supply of high quality drug (Farmer 2001). In some situations, DOT may protect the confidentiality of HIV-infected people.

The availability of once daily regimens has made DOT more viable in the context of HIV. People taking a twice daily regimen may be given medication daily but only observed taking one dose - this is called modified DOT.

Studies have reported 50-85% of people receiving DOT for HIV achieving undetectable viral load (Kirkland 2002; Mitty 2002; Clarke 2002). Not surprisingly, there is evidence that adherence improves significantly when DOT is deployed (Stenzel 2001; Sorensen 1998; Hader 2001).

References

Knobel H et al. Impact of simplification to a lower pill burden HAART in adherence and risk factors for non-adherence. 15th International AIDS Conference, Bangkok, poster presentation, abstract WePeB5773, 2004.

La Paz H et al. Adherence, treatment-satisfaction and effectiveness of once-daily versus twice-daily antiretroviral therapy in a large prospective observational cohort (CUVA Study). 15th International AIDS Conference, Bangkok, abstract WePeB5780, 2004.

Stone VE et al. Perspectives on adherence and simplicity for HIV-infected patients on antiretroviral therapy. J Acquir Immune Defic Syndr 36: 808-816, 2004.