AIDS Treatment Update

starting with N NRTIs
Efavirenz and nevirapine, the two licensed
drugs in this category have become popular
first-line options. In 1998 and 1999, half of
those who began anti-H IV therapy in three
English HIV clinics took an NNRTI-based
three drug regimen, whilst a quarter began a
PI-based triple regimen (see diagram page 8)'.
In addition, the trend for switching off an
existing suppressive regimen to improve
tolerability has favoured these drugs. Both are
simpler regimens than many PIs, and for those
concerned about metabolic abnormalities and
lipodystrophy, there is some evidence that
switching to nevirapine may improve
dysregulated blood lipids. The evidence that
efavirenz can help here too is less strong, and
neither have been convincingly shown to
improve body shape changes. (This subject was
last covered in AIDS Treatment Update issue
87, and will be the subject of a forthcoming

special issue. See also the comprehensive
reviews on our website, aidsmap.com.)
Earlier studies have suggested that efavirenz
may be a more potent first-line therapy than
indinavir. Nevirapine was found comparable to
indinavir therapy in the Atlantic study, and has
also been compared with nelfinavir in the
COMBINE study.
Nevirapine versus nelfinavir
In COMBINE, 142 people who were new to
anti-H IV therapy were randomised to receive
open-label treatment with Combivir plus either
nevirapine or nelfinavir'2. All drugs were taken
twice daily. Median viral load was
approximately 60,000 and median CD4 cell
count was approximately 355 at entry.
After 36 weeks treatment, viral load responses
were better in the nevirapine arm: 67% versus
38% below 20 copies by intent to treat
analysis, and 80% versus 56% in the on
treatment analysis. These differences are wider
than may have been expected given previous
nelfinavir data, and they are not easily
explained. More people stopped their
nelfinavir treatment than stopped nevirapine
(32 versus 24 at 36 weeks), though some of
these switched because of intolerance, roughly
equal numbers in each. A higher number of
nelfinavir users were lost to follow-up (17
versus 10). Fewer nelfinavir users were
reported to be more than 95% adherent to
their treatment in the first month (59% versus
79%). Though its unclear how this was
measured, this may explain the poorer
nelfinavir performance.
Interpreting these data is difficult when the
COMBINE team appear to have allowed
ample opportunity for their study to be
criticised. It's unhelpful that at the start of the
study, more women and heterosexuals were
recruited to the nelfinavir arm than to the
nevirapine arm. It's possible that this failure
to ensure that the two arms were well-matched
may have biased the outcomes.