AIDS Treatment Update

However, another possible explanation is that
nelfinavir is less potent than nevirapine. In a
small subset of 26 nelfinavir users and 21
nevirapine users who began treatment with
viral load above 100,000 copies, a greater
number of the latter had viral load below 50
copies after 36 weeks (15% versus 62%
intent to treat analysis, 27% versus 62% on
treatment analysis).
Efavirenz versus nevirapine
Spanish researchers have presented
preliminary information from the SENC study
comparing efavirenz with nevirapine, both
taken with ddl/d4T'. Over a 24 week period,
the two treatments were found to be broadly
comparable; around 80% had viral load below
50 copies at this point by intent to treat
analysis. However, the sample sizes are very
small; 28 in the nevirapine arm and 26 on
efavirenz. In addition, participants began with
fairly low viral loads, the median being just
over 20,000 copies. For these reasons, it's
very difficult to conclude from these data that
these two NN RTIs are truly equivalent.
Instead it may be wiser to wait the results of
the 2 N N study, ongoing in the U K, which
compares these drugs with a dual NN RTI arm.
The SENC study does however provide some
interesting information on side-effects. In both
treatment groups, there were significant rises
in total cholesterol levels over the study
period. Efavirenz was observed to raise
cholesterol in the efavirenz versus indinavir
comparison study (DuPont's 006 study).
However, this increase was due to a rise in
HDL, or 'good' cholesterol rather than in LDL
or 'bad' cholesterol.
The issue of side-effects may be the best way
to choose between these two drugs in the
absence of clear evidence on efficacy. There is
little to choose between the two in terms of
the simplicity of the regimen. Nevirapine is
one tablet twice a day, efavirenz is three
capsules once a day, and neither require
restrictions on food or fluid intake.

Nevirapine's most significant side-effects are
rash, which tends to appear early in treatment
or not at all, and hepatitis, but the risk is low
and nevirapine users must undergo regular
liver function tests to monitor for this. There is
some evidence that the risk of liver toxicity is
higher in people who also have chronic
hepatitis B or C infection.
Efavirenz's Achilles heel is the significant
level of what are termed 'central nervous
system (CN S) side-effects' - vivid dreams,
euphoria, disorientation, etc. - associated with
its use. According to a recent report from
Australia, their persistence may have been
underestimated'4. 90% of 106 efavirenz users
reported CNS effects in the early weeks of
treatment, and these continued to occur during
long-term follow-up in 40%. It seems many
people persist with the efavirenz treatment
nevertheless, reflecting the need to balance
risks and benefits. Over an average follow-up
of eighteen months, seventeen people stopped
their efavirenz therapy due to CNS effects.
Future NNRTIs
Capravirine, formerly known as AG1549, is an
experimental NN RTI from Agouron which is
being studied alongside nelfinavir, both taken
with Combivir, in people new to treatment.
This blinded study is recruiting in the U K.
Capravirine is taken twice daily, and the sideeffects which have been reported most
frequently are nausea, vomiting and headache.
Emivirine, formerly MKC-442, is an NN RTI
from Triangle Pharmaceuticals. It is not
available in the UK at present. In combination
with ddl/d4T in people new to treatment, it
has reported rather disappointing results".
There is evidence that both efavirenz and
nevirapine are at least comparable to a single
P1-based HAART regimen in people new to
treatment. Whether one is a better choice for
first-line therapy than the other is not
presently known.

references pages 2-10
)th itenai nal
Congrems on DrugO]
Therapy in HIV
Irfectoi, 2000 noted
as G asqo;I 13th
liternational AIDS
Conference/ 2000 as
D,jbar
1 Beck EJ. Glasgow,
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2 Stryker P. Glasoow,
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3 Johnson M. Glascgow,
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4 Rockstroh J. Glasgiow,
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5 Bernsten B. Glasgow,
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6 Chaillon 5.40
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7 Gatell JM0.Durrhai,
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9 Saine 1. 40' ICAAC,
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12 Pordzariczer D. 40"
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13 Nrrez M. 40*
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14 Kelly VI.12'
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15 Jolison D. Dtrbanr
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16 Carn P. 40' ICAAC,
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17 Matherort S.
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