Dr Graham Moyle feature
FAT CHANCE:NEW HOPE FOR LOST
Dr Graeme Moyle of the Chelsea and Westminster Hospital speaks to Robert Fieldhouse
about the latest evidence for drug switching to regain limb fat
LIMB FAT?
Of all the side effects associated with antiretroviral
drugs, body fat changes are perhaps the most stigmatising. But a new study,
the RAVE study, presented at the recent 12th Retroviruses meeting in Boston
offers fresh hope to those living with fat loss from antiretroviral drugs.
PN: Tell us about the background to the RAVE study.
GM: There have already been three published studies where patients switched
from either AZT or d4T to abacavir: the MITOX study and two published in the
Journal of Acquired Immune Deficiency Syndromes (JAIDS); one from Simon Mallall’s
group in Australia and one done at the Chelsea and Westminster Hospital that
demonstrated that switching from a thymidine analogue (d4T or AZT) to abacavir
led to fat recovery.
Those were the only studies where fat recovery had been observed. But we were
concerned that people needed more options to switch to, as not everyone can
tolerate abacavir. We wanted to set up a study which compared against abacavir,
as the standard of care. Obviously, the logical drug to use was tenofovir
given the results of the Gilead 903 study which suggested that, prospectively,
lipoatrophy, or fat loss, did not occur with that drug.
PN: How quickly after switching away from either AZT or d4T did limb fat begin
to return?
GM: We only DEXA-scanned people at week 24 and week 48, but already by week
24, fat had begun to return.
PN: Were patients asked for their opinion about how their body shape
has changed over time?
GM: They were asked, but we haven’t completed the analysis yet. We will
present that at a later point along with the facial scanning done to look
at facial volume.
PN: Had the people previously treated with d4T experienced more fat
loss than those who had used AZT?
GM: It depends which group you look at. In the group treated with abacavir
there were slightly more AZT-treated patients at baseline. The limb fat was
almost identical at the start of the study: 2.72kg in those who had received
d4T and 2.96kg among those who had been treated with AZT. So they were really
quite well matched groups.
PN: As well as looking at rates of undetectable viral load at week
48, you assessed changes in blood fats. What happened?
GM: In the tenofovir group there were falls in lipids that were significantly
greater than the abacavir group with regards to total cholesterol, LDL cholesterol
and triglycerides. The abacavir group effectively did not see any change in
the lipid parameters on average, whereas the tenofovir group saw modest falls
in those parameters. The magnitude of decline in lipids that we saw with tenofovir
was in the range you would expect to see if a patient were to follow dietary
advice. We also noted the people switching away from AZT gained extra red
blood cells; increases of 0.85g/dl with tenofovir and 0.45g/dl with abacavir.
Transfusion with one unit of blood would raise your red blood cell level by
about 1g/dl so it’s quite a substantial improvement.
PN: Are these differences clinically significant?
GM: We know dietary advice is an effective way of managing and preventing
cardiovascular disease. The magnitude of the decline in lipid parameter seen
on tenofovir was one that we would associate with a reduction in cardiovascular
risk. We haven’t yet analysed the proportion of patients in the study
who meet particular National Heart Foundation or National Cholesterol Educational
Panel (NCEP) targets, but we are planning to do this. We don’t know
how many people avoided the need for lipid lowering therapy based on blood
lipid levels as a result of switching.
PN: What proportion of patients had to stop abacavir or tenofovir
and why?
GM: Eight patients or 15 per cent dropped out of the abacavir group, 6 per
cent due to suspected abacavir hypersensitivity reaction. This compares to
three patients or six per cent total of the tenofovir treated group. Only
one patient discontinued tenofovir due to side-effects.
PN: What was the clinical significance of the reduction in bone mineral
density that occurred with tenofovir?
GM: If you look at the median values the change in each of the groups (either
tenofovir or abacavir), the decline in bone mineral density was less than
seven per cent. If you look at the mean values the change was less than 5
per cent, so they are meaningless changes; changes you would expect to see
between summer and winter.
PN: Does this study have any implications for what drug people should
be choosing for their first therapy?
GM: I suppose there is plenty of prospective data (where patients are followed
on a specific treatment over time) on abacavir from both the study published
in JAIDS last month and from the ABCDE study, (which compared abacavir, 3TC
and efavirenz with d4T, 3TC and efavirenz). In terms of data on tenofovir,
the Gilead 903 study, which has reported data for three years, looked at tenofovir
with 3TC and efavirenz and showed tenofovir to be safe from a lipodystrophy
standpoint in long-term prospective use.
But the fact that both of them allow fat to recover, further underlines the
point that they are drugs which are not harmful to limb fat and provide more
options for patients.
