What is adherence?

Adherence means taking your drugs exactly as prescribed. This includes taking them at the right time. It also includes following any special diet restrictions.

If you do this it will help make sure that you have a constant minimum level of each drug. This will be 24 hours a day, 7 days a week, 365 day a year!

Every time that the levels of a drug fall below this minimum level, you are at risk of the virus developing resistance to the drugs in your combination.

• It is important that you develop a routine. Treatment for HIV involves a complicated daily schedule. You may need some support to get used to the changes it makes in your life. Adherence can be very difficult.
• This is the most important thing you have to think about when you start taking a new combination.
• Start treatment when you can give yourself the extra time and space you may need to adjust.
• During the first few weeks, nothing else should take priority over getting your treatment right.

Many treatment centres now have an adherence clinic or an nurse who can help with adherence.

Taking medication exactly on time is very important.

But there is usually a window period of about an hour that is still okay. Some drugs, and some people, have a wider window period than others.

Because of this variation, it is still better to aim for the same time each day.

Diet restrictions are very important. Ignoring these can be like only taking half a dose. You will not absorb enough of the drug for it to work. Resistance is then more likely to occur.

How much is enough?

So, exactly how close to perfect adherence do you have to get? Unfortunately, the answer is almost 100%… but there is still some flexibility.

Many early studies have shown that even missing one or two doses a week can have a big impact on the chances of successful treatment.

One widely quoted study showed that even with 95% adherence only 81% people achieved undetectable viral load. (Paterson and others). That is only one in every 20 doses that was missed or late.

Table 1: Adherence rates and % of people undetectable [1]

Adherence also directly impacts HIV-related mortality. In another study of 950 people starting treatment for the first time, for every 10% decrease in adherence there was a 16% increase in HIV-related death².

On the other hand, a US study of people in prison who took every dose showed much better results. Because these patients were in prison, every dose was supervised. All had viral loads below 400 copies/mL after a year and 85% were below 50 copies/mL.³

This result was more impressive than nearly every clinical trial. Most of these people had already failed previous treatments and so were even less likely to get a good result.

The point is not that you need to be in prison. It is that if you find a way to take all your drugs as prescribed, you will get good results.

• Be strict with yourself in assessing how adherent you are through a regular week.
• If it’s not looking so good, you need more support. You will need to ask.
• Talk to your doctor!

Are some combinations more flexible?

Whatever your combination and whatever your previous treatment history, it is common sense that the best adherence will give you the best chance of long term health. This is especially true when starting treatment and until viral load becomes undetectable.

Once viral load is undetectable and is stable at this level, then someone would have to be very unlucky to develop resistance from missing one dose of meds. So there is some flexibility, and most combinations allow you and hour or two either way when drug levels should still be ok.

If you combination includes three drugs that are cleared more slowly from the body, this window period may be wider still. The only current combination that has shown this benefit in studies is the combination of efavirenz/tenofovir/FTC. This combination is also available in a single formulation called Atripla.

In one study (called the FOTO study) people who had already had an undetectable viral load took Atripla from Monday to Friday but not at weekends. In this study of about 50 people followed for a year, viral load did not rebound and resistance did not develop. This finding is specific to these three drugs. The study is more to show that an occasional missed dose may be okay. Even with these results daily adherence is recommended.

Learning support module — What happens when you take a drug

Learning support module — Drug levels, drug activity and side effects

References

1. Paterson DL et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 133-21-30 (2000).
2. Hogg RS et al. Non-adherence to triple combination therapy is predictive of AIDS and death in HIV-positive men and women. 7th CROI, 2000. Abstract 73.
3. Fischl M et al. Impact of Directly Observed Therapy (DOT) on outcomes in clinical trials. 7th CROI, 2000. Abstract 71.
4. Cohen C et al. The FOTO study: The 48 week extension to assess durability of the strategy of taking efavirenz, tenofovir and emtricitabine five days on, two days off (FOTO) each week in virologically suppressed patients. (Poster abstract MoPeB063.) Paper presented at the Fifth IAS Conference on HIV Pathogenesis, Treatment, and Prevention, 19–22 July 2009, Cape Town, South Africa.
   http://www.ias2009.org/pag/Abstracts.aspx?AID=3046.