Less-than-perfect
adherence to a once-a-day HIV treatment carries five times more risk of
treatment failure than imperfect adherence to a twice-a-day regimen. That’s one
of the surprising things that came out of an adherence conference in Miami at the end of May.
We
assume once-a-day regimens for HIV are a boon. The appearance of Atripla, the first one-pill, once-a-day
treatment for HIV was hailed as a landmark when it was licensed in Europe in 2007. A decade earlier people were taking
handfuls of pills two or three times a day.
A
study 18 months ago showed that adherence was 4.5% better in once-daily than in
twice-daily drug regimens.1 In the NAM
treatment survey in 2008, one in twelve people spontaneously mentioned Atripla or once-a-day dosing as the
thing that most helped with their adherence.
If
you miss a dose of a once-a-day regimen, however, there is a longer gap before
the next one is taken, and researchers at the Miami conference warned that the consequences
of poor adherence may be more serious.2
They
looked at 2410 people who started HIV treatment for the first time between 2003
and 2009 and followed them for an average of 2.5 years, conducting regular
interviews about their adherence with them.
Poor
adherence, defined as missing at least one dose of treatment during the past
month, was reported by patients in one-third of interviews.
More
than one in twelve patients (8%) experienced their viral load ‘rebounding’. The
researchers stratified their patients into whether they missed zero, one, two
or more than two doses; there was no separate analysis of patients who missed very high numbers of doses. For patients
taking a once-daily treatment, missing any dose increased their risk of viral
rebound and this risk increased with the number of doses missed in the past
month.
Not
too surprising: but what was surprising was how much difference missing just
one dose made. In comparison with people who didn’t miss any doses, people who
missed just one dose had five times
the risk of their viral load rising. People who missed two doses had seven
times the risk, and people who missed three or more doses had nine times the
risk. This mattered: people who missed several doses also had a greater risk of
dying in the study period than other people.
Unexpectedly,
the same kind of effects weren’t seen in people taking their treatment twice a
day. In fact, no statistically significant relationships were found between
missed doses and either an increased risk of viral rebound or of death.
So
100% adherence may be easier on a once-a-day regimen but if you do miss doses
the consequences are more serious than on a twice-a-day regimen. For someone
who’s not confident of near-perfect adherence, once-a-day treatment may be more
risky.
Just
the fact that a conference is organised where every single presentation is
about adherence tells you how important it is to successful HIV treatment.
Another
way to get a sense of this is to take a look at some of the ways in which
doctors, researchers and drug companies would like to track people’s adherence
to medication.3
Currently,
methods include just asking patients how many doses they’ve missed, counting
how many pills are left in their container and keeping an eye on how often
people come back to the pharmacy for a new supply. The trouble is, none of
these are foolproof: people almost invariably overestimate their adherence and
can also confound the system by building up pill stockpiles or giving them
away.
There
are devices which record the date and time that a pill container is opened and
show both the total number of doses taken and whether they have been taken on
time. These don’t work if you stock up a weekly pillbox.
Researchers
are now developing devices that use wireless technology to send the information
about when the pill container was opened over a mobile phone network to the
person’s doctor. Speaking at the conference in Miami,
one researcher showed data downloaded to her laptop that morning showing the
exact times that a woman in Uganda
had taken her medication over the past few days. We could see that she had
missed a dose on Saturday morning.
Is
this a step too far? What about privacy and personal autonomy? Advocates say
that such systems have important advantages. Because they collect information
in real time, they can warn doctors of a problem before it’s too late. It’s no
good knowing that a person had a treatment break a month ago. If doctors knew
immediately that a patient was having problems with adherence they could intervene
and offer support in good time. Seeing a couple of missed doses could, for
example, be the trigger for a nurse to phone and see what the problem is.
Some
people don’t think even such a system goes far enough. Hitherto, no method of
monitoring adherence shows whether someone has actually swallowed the drug. So even more high-tech methods are being
developed, embedding a supposedly harmless antenna, mini-magnet or microchip
inside the pill, which sends a signal when swallowed. It might give accurate
data - but would you swallow it?