Compiled by Robert Fieldhouse
Good but imperfect adherence risks failure
People who start HIV therapy with a high viral load,
low CD4 and good but imperfect adherence are more likely to develop drug resistance
than those who began with higher CD4 counts, new research suggests.
The Canadian study followed 1,191 patients for 30 months, all of which began
HIV therapy between 1996 and 1999. The majority of people studied were gay
men in their mid-30s.
Researchers found a quarter developed drug resistance mutations during this
period. The most common mutation was M184V which typically emerges as resistance
to the nucleoside analogues (NRTI) 3TC or FTC develops.
Forty per cent developed resistance to non-nucleoside reverse transcriptase
inhibitors (NNRTIs) such as nevirapine or efavirenz, a third developed resistance
to nukes (NRTIs) and just under a quarter developed resistance to protease
inhibitors.
A quarter developed resistance to more than one class of drug, with resistance
to 3TC/FTC and a NNRTI being the most common.
Those who obtained 80-90 per cent of their prescriptions refills were more
likely to have developed drug resistance than those who obtained only 0-20
per cent. Simply put: if you are not taking the pills, you are less likely
to develop resistance to them. In order to prevent resistance, adherence needs
to be greater than 95 per cent.
People with low drug levels during the first three months of treatment were
more likely to have drug resistance than those whose levels were sufficient.
Testing showed 53 people (7 per cent) had drug resistance before starting
HIV therapy, suggesting they acquired it from sexual partners.
Positive people should
get vaccine first
A scientist who co-discovered the HIV virus has urged vaccine researchers
to concentrate efforts on developing a therapeutic
vaccine for people with HIV first.
Professor Luc Montagnier, president of the World Foundation for Aids Research
and Prevention, said scientists should then use the therapeutic vaccine to
produce a preventative one in an attempt to protect HIV negative people.
Professor Montagnier predicted a therapeutic vaccination would be “a
better substitute for antiretroviral therapy”, especially for patients
in the developing world because they cannot afford treatment.
Currently some 30 vaccines are being tested around the globe, but even the
most advanced are not expected to be available for at least another decade,
according to major
vaccine funder, Bill Gates, founder of Microsoft.
Anna Poppa reports from the European Association
for the Study of Liver Disease (EASL) Meeting
Study points way for HIV/hep C treatment
A third large-scale clinical trial has proved that pegylated
interferon and ribavirin is a more effective treatment for people co-infected
with HIV and hepatitis C virus (HCV) than standard
interferon and ribavirin.
Pegylated interferon can be dosed once weekly as the polyetheylene glycol
(peg) added to alpha interferon slows down its removal from the circulation.
Results from the French RIBAVIC trial support the findings of the APRICOT
and ACTG 5071 studies.
The aim of HCV therapy is to shut off viral replication so when treatment
is stopped, the virus does not reappear in the blood stream. This is called
a ‘sustained virologic response’, or SVR. Of the 412 people in
the RIBAVIC study, 27 per cent achieved an SVR following
a 48-week course of pegylated interferon plus ribavirin, compared to just
20 per cent treated with standard interferon plus ribavirin.
Those infected with forms of HCV more responsive to treatment, genotypes 2
and 3, were more likely to achieve an SVR, though response rates in this group
did not differ according to the type of interferon given.
People with genotypes 1 or 4 did better if given pegylated rather than standard
interferon. There was no difference in the risk of side effects between the
two treatments.
Which interferon
for hep C?
A
study exploring the merits of beginning HCV therapy with
ribavirin plus either Pegasys (pegylated interferon alfa-2a), or PegIntron
(pegylated interferon alfa-2b), has found no differences between the two drugs
when used in routine clinical practice in
people with HCV monoinfection (without HIV).
Of 218 German HCV patients starting treatment for chronic HCV, around half
achieved a sustained virologic response (SVR). The response rate in those
who started Pegasys was similar to that in people starting PegIntron and there
were no differences in the proportions who did not maintain control of their
HCV, or in the likelihood of treatment being stopped early because of a poor
response.
So far, few studies have
compared the two licensed peginterferons in people with HCV, and there is
very little information to guide treatment selection in people coinfected
with HCV and HIV.
A trial designed to provide a more rigorous test of the two drugs’
performance in HCV patients, the IDEAL study, is expected to report initial
results next year.
New hep C drug on
the horizon…
An experimental drug called viramidine may reduce the risk
of developing anaemia during treatment for HCV.
Viramidine is converted to
ribavirin inside the body, and is being developed as an alternative to taking
ribavirin itself.
A study comparing the two in HCV patients receiving pegylated interferon found
people
taking viramidine were less
likely to develop anaemia than those on ribavirin.
Anaemia is the term for a fall in the number of red blood cells in the bloodstream,
and can result in fatigue. Fatigue occurred no less frequently in viramidine
users than those on ribavirin, and the study was too small to provide convincing
evidence that the two drugs have a comparable effect on the activity of HCV.
...and new hep B
drugs,
too
A trial exploring the safety of pradefovir, a drug in early development
for treatment of hepatitis B virus (HBV) infection, found no serious or unexpected
side effects in a small group of HBV patients who took the drug over 28 days.
Pradefovir is a similar drug to adefovir, a licensed HBV treatment. Both are
converted to their active ingredient, PMEA, inside the body. A key difference
is that while adefovir is processed via the kidneys, presenting a small risk
of kidney problems, pradefovir leaves the body via the liver.
A trial comparing the two drugs in people with HBV is underway.
A second experimental HBV drug, valtorcitabine, has also been found to be
well-tolerated in a small clinical trial.
Anna Poppa is a freelance medical writer, annapoppa@tiscali.co.uk
Martin Flynn reports from the 11th annual conference
of the British HIV Association
Four formidable women launch conference
Four powerful and charming women opened the 11th annual conference of the
British HIV Association (BHIVA) with the British Association for Sexual Health
(BASHH) at Dublin City Hall on 20 April.
Pictured (left to right) are Professor Fiona Mulcahy
of St James’s Hospital, Dublin; Mary Harney, Ireland’s deputy
Prime Minister and Minister for Health; Dr Angela Robinson, President of
BASHH from London’s Mortimer Market Centre, and
Dr Margaret Johnson, chair of BHIVA from London’s Royal Free Hospital.
AZT faces fall from grace in new HIV therapy
guidelines…
Top UK HIV doctors are poised to shift away from recommending HIV drug regimens
containing AZT as first-line therapy.
Growing evidence suggests long-term AZT use may contribute to fat loss (lipoatrophy)
that is costly to treat, and this is reflected in the draft 2005 British HIV
Association guidelines.
Professor Brian Gazzard, of the Chelsea and Westminster Hospital, outlined
the changes when he presented the draft at April’s BHIVA/BASHH
conference in Dublin. The guidelines, used by
doctors across the UK when treating people with HIV, suggest people currently
taking AZT should be offered a switch to abacavir or tenofovir. They state:
“Until the situation becomes clearer, the increased likelihood of lipoatrophy
mitigates against the choice of AZT as initial therapy.”
The guidelines discuss the three co-formulated dual NRTI backbones: Combivir
(AZT/3TC), Kivexa (abacavir/3TC) and Truvada (tenofovir/FTC). They acknowledge
AZT/3TC is likely to become considerably cheaper in the next two years as
generic AZT becomes available.
But the guidelines stress continued use of AZT/3TC combinations in future
is likely to depend upon AZT’s propensity to produce lipodystrophy,
“which is in itself costly to treat”.
When it comes to choosing between Kivexa and Truvada, guidelines urge doctors
to discuss with patients about managing abacavir’s short-term toxicity
and weighing this against
tenofovir’s lack of long-term data in clinic populations and its potential
long-term toxicity.
The guidelines add: “In this uncertain situation with no clear data,
the relative costs of the two combinations will legitimately be an important
consideration.”
The guidelines discuss the pros and cons of starting therapy with a
non-nucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease
inhibitor (PI) alongside a dual nucleoside analogue (NRTI) backbone. They
conclude: “More data exists for NNRTI-based regimens in terms of
effectiveness. The guidelines also now favour efavirenz over
nevirapine for first-line therapy.
“The committee believes efavirenz is the NNRTI of choice except for
women who may wish to become pregnant,” the report continues.
“Nevirapine is an alternative in women with a CD4 count of less than
250 and men with a CD4 count below 400, where the risks of serious adverse
reactions are minimised.” The preferred boosted PI is lopinavir/ritonavir
due to its “most robust data” for
potency in a PI-naïve population.
Alternatives include ritonavir-boosted saquinavir and ritonavir-boosted fosamprenavir.
Ritonavir-boosted atazanavir is not currently recommended because of a lack
of data
showing its effectiveness as a first-line therapy. When
it comes to starting therapy, the guidelines do not differ greatly from
the 2003
version they replace.
The guidelines state anyone with symptoms of HIV infection should be offered
treatment regardless of their CD4 count, as should people with CD4 counts
in the 200-350 cell range, even if they do not have symptoms.
People with CD4 counts above 350 cells are not normally offered therapy, unless
they have HIV-related symptoms. Structured treatment interruptions are only
recommended as part of a clinical trial, except for those who began antiretroviral
therapy with a CD4 count higher than 400 cells.
Resistance testing is recommended on the first available blood sample and
after each treatment fails. Final guidelines will be published in the next
few months and Positive Nation will report these in detail in a future edition.
Robert Fieldhouse
Late diagnosis major factor in HIV deaths
Access to HAART has been responsible for a decline in the UK's annual HIV
death rate from a peak of over 1,600 deaths in the mid-1990s to a currently
stable total of around 400 deaths a year.
However, a high proportion of these deaths – about 40 per cent –
occur in people diagnosed with HIV within the previous year. Speaking at the
BHIVA and BASHH conference, Tim Chadborn of the Health Protection Agency (HPA)
said that earlier HIV diagnosis may have prevented death in an estimated 60
per cent of individuals recently diagnosed and 34 per cent of all individuals
who died in 2002.
Individuals diagnosed late in 2002 were approximately 14 times more likely
to die within one year than individuals diagnosed at higher CD4 counts. Mr
Chadborn said that early HIV diagnosis is “critical" if
people are to get benefit from HAART and getting people diagnosed earlier
may help to reduce the further spread of HIV.The researchers highlighted that
in 2002, 26 per cent of gay
men in England and Wales were diagnosed late (with a CD4 count below 200)
compared to half of all heterosexual men and 43 per cent of non-pregnant heterosexual
women.
Pregnant women were less likely (22 per cent of all those diagnosed late)
to be diagnosed with a CD4 count of less than 200 as their HIV infection was
picked up earlier during routine antenatal screening sessions.
…but Combivir wins nuke debate
A
lively GSK-sponsored debate over which nucleoside analogue combination is
best for people starting HAART ended in victory for Combivir.
Dr Martin Fisher, of the Royal Sussex County Hospital, argued that Kivexa
(3TC and
abcavir) the new GSK once-daily pill, was more tolerable than Combivir. Switching
from AZT to abacavir improved lipodystrophy, and the abacavir hypersensitivity
reaction was rare and easy for
doctors to spot, he said.Kivexa costs £374 per patient per month, compared
with £343 for Combivir and £418 for Truvada, Dr Fisher added.
Dr Mike Brady, of King’s College Hospital, said patients preferred Truvada
(tenofovir and FTC) as it was taken once-daily. He pointed out that in a recent
trial comparing Combivir and tenofovir, six per cent of patients stopped Combivir
in the first year because of AZT-related anaemia, a side effect not reported
with tenofovir. Dr Mark Nelson, of the Chelsea and Westminster Hospital, said
Combivir (AZT and 3TC) had proved itself to be effective in more than 30 trials.
He argued it was likely all nucleoside analogue drugs, not just AZT, caused
lipodystrophy. At the end of the debate, half the audiences’ doctors
and charity workers voted for Combivir as the nuke backbone of choice for
the majority of patients starting HAART, while 43 per cent voted for Kivexa.
Patient representatives are top banana
Garry Brough (left) made a big impression at the conference with his talk
about patient involvement in HIV clinics. Gary is the patient rep at London's
Mortimer Market Centre, which supports doctors and nurses as well as helping
patients over issues like adherence, disclosure, body image and self-esteem,
stigma and sex and relationships. Innovative schemes with HIV positive patient
reps have also been launched in Brighton and are now likely to be rolled out
across the country.
words
“AZT does cause
lipodystrophy but at a slower rate than d4T.”
Professor Brian Gazzard, Chelsea and Westminster Hospital.
“There is no evidence at the moment that AZT
causes lipodystrophy.”
Dr Mark Nelson, Chelsea and Westminster Hospital.
“If you switch to abacavir from AZT, lipodystrophy is reversed. Dr Nelson
must be the only HIV doctor in Britain who doesn’t believe AZT causes
lipodystrophy.”
Dr Martin Fisher, Brighton and sussex univeristy
hospitals.
“How we stop HIV drugs
is as important as how
we start them.”
Professor Bill Powderly, University College Dublin.
“The greater your sexual network, the greater your risk of catching
a sexually transmitted infection. It’s not your partners that
matter but your partner’s, partner’s partner.”
Dr Helen Ward, Imperial College London
“Treatment decisions will be cost-driven as we become more cost
conscious.”
Professor Brian Gazzard, Chelsea and westminster
hospital
