Compiled by Robert Fieldhouse
Tipranavir performance enhanced by T-20
People
with resistance to PIs who took tipranavir alongside antiretrovirals chosen
by resistance testing were almost twice as likely to get a one log drop in
their virus, as those on existing boosted PIs, new data show.
A one log drop is a ten-fold change, for example from 100,000 to 10,000 copies.
Twenty-four week data from one of two Boehringer Ingelheim studies evaluating
their PI were presented at the at the ICAAC conference in Washington last
month.
Their first data comes hot on the heels of the company’s application
for licensing in both the US and Europe.
The study was carried out in 620 people with HIV with an average prior use
of 12 antiretroviral drugs, in the US, Canada and Australia.
A quarter of those treated with tipranavir got a viral load below 50 copies,
compared with 10 per cent of those who received a comparator PI.
CD4 cell rises over the six month period were also higher among those treated
with tipranavir (36 compared with six cells).
Side-effects such as nausea, diarrhoea and elevated liver function, triglycerides
and cholesterol were reported more frequently among people taking tipranavir
than comparator PIs.
Use of the fusion inhibitor T-20 substantially increased the chance of getting
a viral load below detection.
By adding T-20 to tipranavir, the proportion of individuals whose viral load
went below 400 copies increased to 47 per cent (up from 35 per cent if they
only received tipranavir), and one third of those who received T-20 went below
50 copies (by comparison one quarter of those who received only tipranavir
went below 50 copies).
Tenofovir and Trizivir potent as first therapy
A new study suggests Trizivir is suitable for first line HIV therapy
if it is taken with tenofovir.
This all-nuke combination of AZT, 3TC and abacavir alone was last year shown
to be a less potent and effective first-line treatment than the ‘current
gold standard’ of Combivir (AZT, 3TC) and efavirenz.
In response, British HIV Association guidance was amended to no longer recommend
the use of Trizivir for those beginning HIV therapy.
But taking the once daily nucleotide reverse transcriptase inhibitor tenofovir
with Trizivir appears to make the option as potent and as effective as the
current ‘gold standard.’
A key advantage to this simple all-nuke combo is that it leaves the other
drug classes available for future therapy. A total of 113 people who had never
used combination therapy were enrolled in the trial. The average CD4 count
in those receiving tenofovir/Trizivir was 153 cells compared with 194 cells
in those treated with Combivir/efavirenz.
Average viral load was 180,000 among those treated with tenofovir/Trizivir
and 130,000 among those treated with Combivir/efavirenz.
At week 48, just over two thirds of participants randomised to both treatment
arms had a viral load below 50 copies.
A third of participants in each treatment arm had stopped the trial, though
higher proportions (16 per cent compared with 11 per cent) had discontinued
Trizivir due to side-effects, particularly abacavir hypersensitivity reaction.
CD4 gains over the 48 weeks were higher among those treated with tenofovir/Trizivir
(165 cells) than among those treated with Combivir/efavirenz (119).
Few babies born with HIV in UK & Ireland
Nearly
1,000 children were born to HIV positive mothers in the UK and Eire in 2003
but few were infected with HIV.
There has been a dramatic increase in the number of infants born to women
diagnosed with HIV in this country over the last few years, said Dr Tookey
from the Institute of Child Health at Autumn’s BHIVA meeting.
One in 200 (0.5 per cent) women who had babies in London last year were HIV
positive.
More than 50 per cent of the mums who knew about their infection were on HAART
at conception and more than 95 per cent of all HIV positive expectant women
in the UK are on HAART during pregnancy.
All ante natal units in Britain and Ireland now offer and recommend testing
for all pregnant women.
However some babies will be born with HIV to women who do not know their status.
“We are now diagnosing most HIV positive women because of the recommendation
to test all pregnant women,” said Dr Tookey.
Martin Flynn
ddI-efavirenz-tenofovir fails as first therapy
Initial therapy including once daily ddI, efavirenz and tenofovir
leads to an unacceptably high failure rate, a new hospital-based study suggests.
The study conducted at Chelsea and Westminster hospital by Dr Graeme Moyle
confirms an earlier report from a Spanish study involving 36 people on first-line
therapy.
All participants were new to HIV therapy and were randomised to receive either
tenofovir or 3TC with ddI and efavirenz.
Those who received tenofovir took a lower dose of ddI (250mg) with food, while
those who got 3TC took ddI (400mg) once daily on an empty stomach.
The median CD4 count was 158 cells in the 3TC arm and 174 in the tenofovir
arm at the outset. Viral load was around 100,000 in both groups.
Despite excellent adherence in both study groups, five of the 44 treated with
ddI-efavirenz-tenofovir experienced virological failure at week 48.
All of them had started the trial with CD4 counts below 200 cells and viral
load above 100,000 copies. By comparison, none of the 36 people treated with
ddI, efavirenz, 3TC experienced treatment failure.
If you are currently taking this combination, it may be sensible to discuss
these findings with your doctor.
Tolerability of tenofovir key to success
vs AZT
Early data from a study comparing tenofovir/FTC/efavirenz against Combivir/efavirenz
highlight how your chance of responding to HIV treatment is closely linked
to how easy the therapy is to take and tolerate.
At 24 weeks, 87 per cent of those receiving tenofovir-FTC-efavirenz had a
viral load below 400 copies, compared to 78 per cent of those receiving Combivir/efavirenz.
In total 73 per cent compared with 65 per cent went below 50 copies.
This difference was driven largely by discontinuations from the trial. Twice
as many on Combivir/efavirenz discontinued compared with those on tenofovir-FTC-efavirenz
(21 per cent compared with 11 per cent).
And three times as many people discontinued Combivir-efavirenz over tenofovir-FTC-efavirenz
due to side-effects (nine per cent compared with three per cent).
There was little difference in the chance of having an undetectable viral
load if you were able to tolerate your regimen and stay with it; almost all
participants who stayed on therapy in each arm were undetectable at 24 weeks.
CD4 gains were similar; 129 cells with tenofovir-FTC-efavirenz and 111 cells
with Combivir-efavirenz.
Anaemia associated with Combivir treatment appears to be the side-effect which
prompted the majority of side-effect related discontinuations. The trial will
continue for 48 weeks.
Long wait for HCV drugs in some HIV clinics
Only
three fifths of UK HIV clinics are offering hep C viral load testing and a
fifth have restrictions on treatments because of a lack of funding or a lack
of expertise.
The BHIVA audit of 100 HIV centres around the country, found more than half
of the clinics had at least 15 per cent more HIV patients in 2003 than in
the preceding year.
Seventeen of the centres did not offer hep B viral load testing. Half the
centres said their local hep C rate among HIV positive patients was less than
3 per cent, despite national rates of between 5 and 10 per cent.
Ninety-four out of the 100 clinics now routinely test all HIV patients for
HCV, but 23 of the centres had waiting times for treatment of more than six
months.
Even more worrying is the fact that there is “inappropriate use of drugs
in certain centres,” Dr de Silva said, presenting the audit.
UK estimates suggest that 8-10 per cent of people with HIV in Britain also
have HCV but the EuroSIDA study estimates that as many as one third of people
with HIV across Europe also have hepatitis C. Martin Flynn
Tenofovir/Trizivir effective for second-line
treatment
Trizivir with tenofovir appears a safe and well-tolerated option for
people whose first-line NNRTI or PI therapy has failed.
Twenty-four week data are available for 43 of the 51 patients enrolled in
the study. The data show three quarters of those who switched to the all-nuke
combo had a viral load below 400 copies at 24 weeks and two thirds had a viral
load below 50 copies.
The potential advantage in switching to this combination may be that it preserves
other classes for later use.
T-20 evaluated for once daily dosing
T-20 is currently taken as a twice-daily injection. A small study has evaluated
if the first and only fusion inhibitor could be dosed once daily. Researchers
found no difference in total daily exposure to the drug, but the lowest level
ever reached prior to next dose was 57 per cent lower among those who took
the drug once daily. Further study is underway to confirm that T-20 is safe
and maintains potency if dosed once daily.
Lopinavir-ritonavir capsules deteriorate in heat and
humidity
Researchers have tested lopinavir-ritonavir capsules in their containers at
high temperatures and high humidity. When compared to capsules stored at 40C,
lopinavir
content remained above 95 per cent potency at both 350 and
450C for up to 30 days. By day 60, content had fallen below 85 per cent, prompting
researchers to
recommend that no more than 30 days of lopinavir be prescribed to individuals
living in or travelling
to hot countries with lack of
accessible refrigeration.
FTC ‘safe and effective’ long-term
Three year data from a study where participants either continued on FTC and
AZT plus an NNRTI or a PI, or switched from 3TC to FTC along with AZT plus
their current NNRTI or PI, found no significant differences in efficacy and
safety between FTC and 3TC. FTC is also active against hep B.
Treatment breaks on NNRTIs more risky than PIs
People who take breaks from NNRTI therapy appear less likely to fully suppress
their virus three months after re-starting treatment than people re-starting
protease inhibitor (PI) therapy.
Researchers compared viral load results three months after re-initiating therapy
following a treatment interruption in 34 individuals who re-started NNRTI
treatment. Only 15 of 34 (44%) achieved an undetectable viral load (below
50) at this point, compared to all of the 11 individuals who had stopped and
restarted protease inhibitor therapy. A high proportion of people who re-started
NNRTI therapy had developed resistance to nucleoside analogues during the
interruption. Additionally, 83 per cent of those who switched to NNRTI therapy
following an interruption of PI therapy also had detectable virus three months
after re-starting therapy.This group also developed nucleoside analogue resistance
during the interruption, which researchers suggest led to the failure of subsequent
NNRTI therapy.
Anybody stopping NNRTI-based therapy should continue their nucleosides for
at least two weeks to try to reduce emergence
of drug resistance.
AZT and d4T damage fat cells prior to fat
loss
New research shows that the nucleoside analogues AZT & d4T damage fat
cells before physical signs become visible. These drugs damage the mitochondria
which generate energy within cells. Researchers compared mitochondrial DNA
levels in 41 people who have never used treatment, 38 who were using AZT,
30 on d4T as well as 24 people whose first line therapy includes nukes other
than AZT or d4T. They observed a 60 per cent decline in the mitochondrial
content of fat cells among those treated with both AZT and d4T over a six
to twelve month period. People who began treatment with either tenofovir or
abacavir showed no evidence of mitochondrial DNA loss. Researchers warned
that the mitochondrial DNA is a ‘triggering event’ for the longer
term trend of fat loss.
