Leading Edge
Epilepsy and HIV—a dangerous combination
Recently, the past president of the International League
Against Epilepsy has called for prospective research
and a plan of action to tackle a growing problem
in the developing world. This problem concerns
possible interactions of antiepileptic drugs (AEDs)
with antiretroviral therapies for HIV when given in
combination.
The prevalence of HIV and epilepsy is high in many
developing countries, particularly in sub-Saharan
Africa. Phenobarbitone is the main choice for seizure
control in these regions, in part owing to its very low
cost. Phenobarbitone and some other older generation
AEDs, most notably carbamazepine, phenytoin, and
primidone, are classed as enzyme-inducing because
of their effects on the CYP450 enzyme system, which
is involved in drug metabolism. Consequently these
AEDs can cause changes in the active doses of other
drugs in the body. Administration of phenobarbitone in
conjunction with antiretroviral drugs such as Triomune,
one of the few multidrug regimens for HIV available in
sub-Saharan Africa, can result in a decrease in the half-
life of one of the antiretroviral components, nevirapine.
At present, data on the extent of the effect on
antiretroviral drugs are scarce but, if nevirapine is
decreased to subtherapeutic concentrations, several
consequences are probable. The decreased efficacy of
nevirapine is likely to lead to failure of antiretroviral
therapy for HIV, and this in turn would lead to an
increase in HIV resistance to nevirapine. Moreover, since
HIV can cause seizures, including status epilepticus,
poor virus control would be expected to increase
the incidence of seizures. By contrast, in developed
countries HIV prevalence is lower and epilepsy is more
commonly controlled with newer non-enzyme-inducing
AEDs. Patients also have better access to facilities where
careful monitoring of drug concentrations is possible.
Developing countries could face a stark choice: treat one
condition or risk treating neither.
This situation might result in a knee-jerk reaction
to stop epilepsy medication altogether to allow the
antiretrovirals to work. If patients or health officials
are faced with a choice of which condition to treat,
neurologists are worried that HIV/AIDS might be the
probable candidate, being perceived as the more life-
threatening disease. However, the huge ramifications of
http://neurology.thelancet.com Vol 6 September 2007
uncontrolled epilepsy must also be considered. Epilepsy For the letter from the ILAE
past president see Epilepsia
has a negative stigma and, in addition to the substantial 2007; 48: 1425
consequences for morbidity and mortality, has been
suggested to have major effects on both social and For more on the epilepsy in
Africa see Lancet Neurol 2007;
economic aspects of life for patients in the developing 6: 39–44
world. These include poorer employment, education,
housing, and environment, in addition to problems
with personal safety such as increased rape incidence.
If AEDs were discontinued to allow antiretrovirals to
work, cessation would probably not be undertaken in a
controlled and tapered manner with careful monitoring,
and although the full consequences of sudden cessation
of this medication are not yet known, withdrawal
seizures and status epilepticus are likely.
Prospective research would indeed be useful to
investigate the interactions between enzyme-inducing For more on AED interactions
see Lancet Neurol 2003;
AEDs and antiretrovirals more thoroughly. However, 2: 347–56 and 473–81
research funding bodies and pharmaceutical firms are
unlikely to consider this a high priority. Phenobarbitone
is no longer a first-choice drug for developed countries,
with newer, non-enzyme-inducing AEDs such as
lamotrigine and levetiracetam being more commonly
prescribed. It will also take considerable time to
undertake prospective studies of this nature, and in the
meantime, the health of many individuals will probably
be compromised.
It is tempting to think that the answer might be to
encourage production of generic non-enzyme-inducing
AEDs. However, this is unlikely to be the solution, at least
in the short term. One reason is that these newer drugs,
many still currently under patent, are unlikely to prove
as cheap as phenobarbitone, and even in their cheapest
possible form are expected to be prohibitively expensive
without subsidisation for countries with a low budget
for health per person. In addition, these drugs might
interact with antiretroviral agents, despite their different
mode of action, and thus present their own problems.
WHO is now planning a global antiretroviral
pharmacovigilance protocol and network, and this
specific issue should be considered for addition.Crucially,
epilepsy should not be perceived as the unimportant
condition, and treatment stopped as a result. HIV and
epilepsy researchers must now work together urgently to
find an alternative that does not force epilepsy patients
with HIV to make a bleak choice. ■ The Lancet Neurology
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