Questions and Answers with NAM Christofher Gadd, senior editor, NAM
Tenofovir/ddI warning
My doctor wants me to switch my HIV drug combination because
of a new interaction. I’m on efavirenz, tenofovir and ddI. What’s
going on?
Your doctor is probably concerned about you taking tenofovir (Viread) and
ddI (didanosine, Videx/VidexEC) together. Recent studies show taking these
drugs together can be dangerous. The manufacturers, Gilead Sciences and Bristol-Myers
Squibb, are so worried about the risks of taking these drugs together, they
sent a letter to doctors in March advising them not to give both drugs to
patients. The European Medicines Agency then published a public statement
in April that advised doctors not to co-administer the two drugs.
So what are the risks of taking them together?
Over the past couple of years, a number of clinical studies have shown patients
taking tenofovir and ddI together are at a high risk of treatment failure.
This means the levels of HIV in the blood may begin to rise, leading to drug
resistance. It also looks like taking tenofovir and ddI together increases
levels of ddI in
the body. This increases your risk of dangerous and unpleasant side effects
like pancreatitis (inflammation of the pancreas) and lactic acidosis (elevation
of lactic acid levels in the blood). These are rare, but occasionally fatal.
These studies provided enough evidence to indicate that combining the drugs
could be dangerous, leading to the unusual step taken by the two drug companies.
Concerns raised by these trials were backed up by results from some smaller
studies reporting unexpected falls in CD4 counts in patients taking the two
drugs. These occurred even in patients with good drug adherence and undetectable
viral loads. Experts are not clear why this happens, but it might have something
to do with the CD4 T-cells ‘committing suicide’ due to a complex
interaction between increased ddI levels and certain enzymes inside the cells.
I’m getting on fine with my combination, and don’t really
want to change. Who has the greatest chance of having problems?
The interaction warnings came from
studies involving people with HIV taking a first-line drug regimen including
tenofovir, ddI and a non-nucleoside reverse transcriptase inhibitor (NNRTI)
like efavirenz (Sustiva) or nevirapine (Viramune). Most started with high
viral loads and low CD4 counts, suggesting that this group of patients are
at a high risk.
However, the manufacturers and drug regulatory authorities are taking the
risks of this combination so seriously that their warning was extended to
all patients. They have stated that the two drugs should not be used together
by any patient, not just by those taking an NNRTI or those on their first
anti-HIV drug regimen. A greater risk of treatment failure can’t be
ruled out in other groups, including people who have taken many other anti-HIV
drugs in the past or who are combining tenofovir and ddI with a
protease inhibitor. So, even if you don’t feel like changing regimens,
it would be unwise to ignore your doctor’s advice.
What about people who don’t have enough other drugs available
to come off this combination?
It’s true some patients may not have any other options open to them
and need to carry on taking tenofovir with ddI. Patients in this situation
should continue to take both drugs until new treatment options become available.
In the meantime, they should be monitored closely to ensure the drugs are
still working and that they are not developing any side effects.
I think I’ve got quite a few drugs options still available.
Should
I stop taking tenofovir and ddI straightaway?
Definitely not. You should only change your drug regimen after you have discussed
options with your HIV doctor and decided together how and when to switch to
a new drug regimen. If you stop taking one or both of these drugs without
replacing them with another active drug, you will run the risk of your treatment
failing very rapidly. This will probably lead to drug resistance and limit
the treatment options available to you in the future.
• NAM provides information to help you think about your use of HIV
treatments, but this is not intended to replace discussion with your doctor.
Visit NAM at www.aidsmap.com
