With modern treatment,
people with HIV can expect to live for decades and decades. But is this
sustainable? How realistic is it to expect the drugs to work over a lifetime
and for people to continue to adhere to their treatment regimen throughout?
What are the risks of drug resistance and treatment failure occurring during
long-term treatment?
Combination therapy
has been in use for not even 15 years, so any answers can only be preliminary. But
two large British studies, just published, have shed some light on these
important questions.
The first gives us a
reason to be optimistic. It comes from a single hospital in London (the Royal Free) and tracked adherence
in its patients over several years.1
It’s often thought
that treatment adherence (in other words, not missing doses nor taking them
late) is likely to deteriorate when people take treatment for a number of
years. It may be hard to maintain motivation over a long period. What’s more,
doctors for a wide range of medical conditions have observed that people tend
to be less adherent when they don’t feel unwell (it may not be so obvious why
the drugs are needed).
The researchers
collected information on just over 2000 patients for an average of four and a
half years. Some patients’ adherence was monitored for as long as nine years.
Adherence was monitored in six-monthly periods, and calculated as the
proportion of days covered by a dispensed prescription for at least three drugs
(as correctly taking doses of all drugs in a combination is important).
It’s often said that a
minimum of 95% adherence is needed for treatment to be effective. Here, overall,
92% of doses were taken.
Adherence in the group
has been better since 2005 than it was in previous years. Compared to gay men,
adherence tended to be better in black women and poorer in black heterosexual
men.
However, the headline
finding was that adherence didn’t drop the longer someone was on treatment. In
fact, the reverse: the chances of a patient remaining adherent increased by
about 2% each year.
What’s more, the older
someone was, the more likely they were to stick to their treatment. Other
studies have found that older people are more likely to attend their
appointments and to recognise the medical consequences of poor adherence.
But while overall
adherence was good, one concern is that half the Royal Free patients
experienced at least one period of poor adherence. This was often a one-off
event, a few weeks or months when adherence was not as consistent as at other times.
The researchers
advocate close monitoring of people’s adherence. The concern is that even a
single, relatively short period of poor adherence can, in some cases, give rise
to the development of drug resistance.
That finding may help
us interpret the results of the second study, which are somewhat less
optimistic. The researchers collected data on treatment failure and drug
resistance in almost 8000 patients at eleven large HIV clinics in England and Scotland. Data were collected on
individuals for up to eight years.2
The researchers
defined virological failure as having two consecutive viral load results above
400 copies/ml (but not within the first six months of taking treatment). After
eight years, over a quarter (28%) of people had experienced virological failure
at least once, and would have needed to change treatment.
The researchers also
found that 17% of people had some drug-resistant virus. People who had taken
non-nucleoside reverse transcriptase inhibitors (NNRTIs such as efavirenz) were
more likely to have resistance than those taking protease inhibitors.
However, as in the
previous study, the older someone was, the less likely they were to have
drug-resistant virus. Again, women had better results than men.
People who had low CD4
counts and high viral loads when they started treatment (i.e. people who started
treatment relatively late) had a much greater risk of having drug-resistant
virus than other people.
The researchers express
concern that an appreciable number of people have these problems with the drugs
that are routinely recommended for people starting treatment. Resistance which
emerges today will limit the range of drugs that will be effective in the
future.
But is the glass
half-full or half-empty? If three out of ten people have treatment failure,
that means that seven out of ten don’t. What’s more, in this country, alternative
treatment regimens are almost always available. Doctors are right not to be
complacent, but these two studies do tell us that a significant number of UK patients are
able, over a period of almost a decade, to adhere to their treatment and keep
their viral load suppressed.