Does the premature end of two treatments
interruption trials signal that people with HIV should no longer consider
taking drug ‘holidays’? Jeff Williams reports
Illustrations Jay Obrecht
Many
of us taking HIV meds for many years may recall hearing at some time or other
how we may not have to take the pills for the rest of our lives. This was
because HIV medicine technology was constantly improving. Magazines and newsletters
printed optimistic articles about treatment interruptions, where a patient
would take pills for a certain period, then stop for a while, and start again.
This treatment cycle would be repeated as necessary.
Waiting for a breakthrough
The ultimate goal of testing these so-called ‘drug holidays’ was
to see if HIV could be made more manageable for people by enabling them to
stop and start therapy in a medically supervised way. We were
confidently told research on drug holidays was ongoing and that breakthroughs
were just around the corner.
There are many reasons why someone living with HIV might want or need to take
a treatment break. Long-term drug side effects can be debilitating, and many
of us long for some escape from these. Taking HIV meds while travelling poses
its own set of challenges. We may struggle to adhere to our drug regimens
while out of our usual routine, while travelling through time zones or risk
exposing our HIV positive status to immigration and customs officials in countries
with entry restrictions.
Not without risks
Lately, this idea of moving from continuous treatment to treatment interruptions
has taken a big, perhaps terminal, body blow. Over the last few months we
have heard that clinical trials, designed to test the validity of drug holidays
have clearly shown they are not without risks.
The SMART (Strategies for Management of Antiretroviral Therapy) trial, was
the largest ever study designed to observe the effect of regular treatment
interruptions on the health of a large number of people living with HIV. Supposed
to last nine years, it was stopped after only two when it became clear people
randomised to interrupt their treatment were more likely to fall ill.
People in the trial who took a break from their treatments were expected to
restart when their CD4 count fell below 250, then take another break when
the count climbed back up to 350.
Researchers found the number of cases of disease progression (such as opportunistic
infections) was low in those taking continuous medication as well as those
taking treatment breaks. Despite this, cases of
disease progression in the group taking treatment breaks were sufficiently
higher than those on continuous treatment for researchers to stop the trial
early. There were far more deaths and Aids cases in those who took interruptions;
one in 27 compared to one in 67 for those that stayed on continuous therapy.
Continuing with the trial to collect more data could not be justified as it
would not have altered the conclusion that taking treatment with breaks was
inferior to continuous treatment.
A double blow for Africa
More recently, it emerged researchers in Africa were also forced to stop the
part of their major clinical trial looking at treatment interruptions after
finding people taking breaks did worse than people on continuous treatment.
The poor response to treatment interruptions in the Development of Antiretroviral
Treatment (DART) trial in Africa was doubly disappointing. This is because
intermittent therapy is cheaper than continuous treatment. Had it been shown
safe, intermittent therapy could have helped to make access to treatment for
all in the developing world far more likely.
Of course, set-backs like these are unlikely to stop people living with HIV
wishing or needing to take a break from the medication. Both of these clinical
trails were guided by CD4 count only, not by viral load, suggesting a measure
of just one blood indicator of disease progression is insufficient to gain
a full picture of what is going on in our bodies during treatment.
A holiday with payback
Back in 2002, I planned to visit the US for a long holiday and wanted to avoid
any ‘unpleasantness’ at customs and immigration on entry. I gave
the idea of a treatment break careful consideration and discussed it with
my doctor. He agreed I should try it, but only if my blood was monitored more
frequently than normal.
In my case, this caveat turned out to be crucial. Things can change very rapidly
when you come off therapy. When I stopped the drugs on the evening of 2 February
2003, after six years on therapy, I had a CD4 count of 571 and undetectable
viral load. Eighteen days later, my CD4 count was 351 and my viral load was
10,000. By the time I had returned from the US on 2 April 2003, my CD4 count
was 207 and viral load was over 100,000. Just two months later.
I had no choice but to restart therapy as soon as possible. Even after restarting,
my CD4 count did not leap back to its February level. Instead, it climbed
slowly back over 12 months. Typically, people lose CD4 cells
far more quickly than they regain them when restarting therapy.
This slow recovery of CD4 count may well be a widespread characteristic and
some suggest this is the explanation for the apparent failure of the treatment
interruption approach in the SMART trial.
An
opportunity for resistance
Stopping therapy, even for relatively short periods, can result in rapid and,
perhaps, dangerous falls in immune protection, as I found to my cost. As well
as this, our bodies metabolise the various drugs that make up combination
treatment at different rates. This is why some HIV drugs are taken
once or twice a day. If you stop all your medications at the same time it
may lead to resistant strains of virus developing. This could mean that when
you restart therapy, the combination you were on may no longer be effective
at fighting and controlling the HIV.
If you plan to take a treatment interruption it’s essential you talk
to you doctor because you will need to take drug resistance tests. Before
and after my interruption, the clinic monitored the genetic make-up of the
virus in my blood. Fortunately, I did not develop any drug resistance when
I stopped my pills. But it was important I underwent these tests because although
my viral load fell rapidly after restarting therapy, my CD4 count remained
much lower than it had been, which could be taken as evidence of drug resistant
strains of virus.
Starting over
I have to say my relatively short treatment interruption is not something
I would be willing to repeat too often. On starting treatment in the late
1990s, it took two weeks for me to become accustomed to and learn to deal
with the side effects. After my treatment break, I had to deal with this learning
process all over again when I restarted the same medication. On top of this,
after stopping therapy, I suffered a period of ill health caused by my immune
system dealing with the absence of the medication. Luckily my doctor was able
to warn me about these novel experiences beforehand.
The future of trials
So, is this the end for treatment interruptions? Maybe not. Just because the
SMART and DART trials were stopped it does not mean treatment interruptions
are not an option for some of us living with HIV. And a few people appear
to do well on them.
It’s worth pointing out most SMART trial participants were treatment
experienced. So researchers will still want to see how interruptions work
in people with much less treatment experience as part of long-term treatment
management. Finding out how and when therapy can be interrupted safely and
which patients may benefit are important questions that need to be explored
in future trials. But regardless of whether you are new to treatment or have
been on it for years and want to take a break from the meds, always talk to
your doctor. After all, that’s what they’re there for.
