Compiled by Robert Fieldhouse
HAART linked to high blood pressure
Using highly active antiretroviral therapy (HAART) for more than two
years may increase the risk of high blood pressure, a new study suggests.
The findings have reinforced existing concerns that people on HAART may be
at greater risk of heart disease and strokes.
Investigators analysed the records of over 5,500 HIV
positive gay men in the US, recruited between 1984 and 1995.
Researchers were unable to conclude that any particular class of drug contributed
more to increasing the risk.
The men, a majority white and in their early thirties, had their blood
pressure measured every six months. Almost two thirds were smokers.
Researchers warned against reading too much into the findings as weight gain
in the men on long-term HAART could also explain the increased risk of high
blood pressure.
However, these new findings re-emphasise the importance of getting your blood
pressure checked regularly.
A blood pressure measurement is expressed as two numbers, one number presented
‘over’ the other. The ‘top’ number is recorded when
the heart is
beating, the ‘bottom’ is recorded between the heartbeats. High
blood pressure is defined as a reading more than 140/90.
Nuke-free combo
proves effective
Combining lopinavir (Kaletra), a ritonavir-boosted protease inhibitor,
with the non-nuke efavirenz (Sustiva) is an effective treatment for people
starting therapy, according to a new study.
This combination is attractive as it spares the use of drugs from the nucleoside
analogue family like AZT, potentially avoiding side effects such as fat loss
and
nerve damage.
A small preliminary French study looked at 86 adults over 48 weeks. Participants
started the trial with an average viral load of just under 75,000 copies.
By the end, almost three out of four participants had a viral load below 400
while 69 per cent had viral loads below 50 copies. This response is similar
to what you would expect from potent triple-combination therapy.
CD4 gains during the study were also good. The average CD4 count at the start
was 311 cells. These rose by an average of 238 cells by week 48. 
One in four participants dropped out of the trial; a third of these due to
efavirenz-related central nervous system side effects or associated rash.
One patient stopped due to suspected lopinavir-ritonavir side effects.
Blood fats such as cholesterol and triglycerides rose during the first eight
weeks but remained stable for the rest of the trial. HDL, ‘good’
cholesterol levels, increased significantly over the duration of the study.
A nuke-free trial of lopinavir-ritonavir and the NNRTI nevirapine is currently
enrolling at the Royal Free Hospital, London.
If you have not used therapy before and would like to avoid nukes in your
first line therapy, this trial may be a good option. For more info, contact
the research nurses at the Ian Charelson Centre at the Royal Free Hospital.
Drug giant in move
to speed up vaccine
A global HIV vaccine agency has linked up with pharmaceutical giant GlaxoSmithKline
to push forward development of an effective HIV vaccine.
The International AIDS Vaccines Initiative (IAVI) has announced a public-private
partnership with GSK’s Belgium-based vaccine division.
The collaboration is a major breakthrough for IAVI as it is the first time
it has linked up with a major pharmaceutical company. The arrangement will
allow GSK to further develop its
non-primate human adenovirus vaccine vector. These vectors are developed from
adenoviruses (such as the common cold), altered to be non-infectious.
The overall goal is to develop a vaccine effective against all strains of
HIV, but preliminary research will focus on the development of a vaccine protective
against strains circulating in Africa.
The announcement came a few weeks ahead of the G8 summit in Scotland, where
the world’s most powerful leaders committed to HIV treatment for all
by 2010 (see page 12 for full details).
UK International Development Secretary, Hilary Benn said: “An Aids vaccine
is essential in the fight against disease and extreme poverty in the developing
world, particularly in Africa.”
Access widens to
new protease inhibitor
People running out of treatment options are to get better access
to a new, experimental protease inhibitor.
Pharmaceutical firm Tibotec has announced plans to widen access to its investigational
protease inhibitor TMC-114 this autumn.
The company is expected to seek European and US approval for the drug early
next year on the basis of 24-week results from the latest phase of the study
where patients were randomised to get one of four doses of the drug.
Data based on the first 151 patients reaching 24 weeks prompted Tibotec to
push ahead with the twice daily 600mg TMC-114 dose with a 100mg boosting dose
of ritonavir into large trials.
These trials are now recruiting worldwide. The drug will be
studied in both people who are starting HAART for the first time and in the
treatment-experienced.
Initially, the drug is likely to be licensed for protease-inhibitor experienced
patients. It will be marketed in the UK by Janssen-Cilag, a subsidiary of
drug giant Johnson & Johnson.
Some clinics still
offering T-20 too late
Some clinics in the UK are holding back prescribing the fusion inhibitor T-20
until a point when patients are least likely to get benefit from it, a study
suggests.
Some patients are only being offered the injectable HIV drug when they have
few or no other drugs to take it with. Researchers from Brighton and Sussex
University Hospital audited ‘real-life’ clinical use of T-20 among
65 people in 11 UK HIV treatment centres. They concluded the drug should be
used earlier in people who have used all three other antiretroviral classes
(nukes, NNRTIs and protease inhibitors) as this would probably lead to more
favourable outcomes such as good CD4 increases.
Previous large clinical trials evaluating T-20 in treatment-experienced patients
have shown it is possible to identify patients likely to get a lasting response
from T-20.
You are most likely to get a good response if you begin T-20 with a viral
load of less than 100,000 copies, have a CD4 count above 100 cells, have used
fewer than ten antiretroviral drugs in the past and still have at least two
active drugs to combine with T-20.
Presenting the audit at the annual National HIV Nurses Association conference
in Bristol, Nicky Perry, research manager at the Brighton and Sussex University
Hospital, said the audit showed if people had all four of these predictive
factors, two thirds became undetectable after 24 weeks of treatment with T-20
and other antiretroviral drugs. This is a great response if you are highly
treatment-experienced.
On the other hand, it may be sensible for those with no other active drugs
available to
combine with T-20, to wait for new drugs to become available.
These include the investigational protease inhibitors tipranavir, TMC-114
(see above) or the investigational non-nuke TMC-125.
medical notes
New PI tipranavir wins US licence
The investigational protease inhibitor tipranavir (Aptivus) has won
fast-track approval in the US for adults with HIV resistant to other protease
inhibitors.
Two clinical trials in people who have previously used protease inhibitors
showed tipranavir to be more effective over 24 weeks of therapy than existing
PIs like lopinavir or saquinavir.
The approved dose is 500mg of tipranavir twice daily with a 200mg boosting
dose of ritonavir. The US Food and Drug Administration (FDA) asked for further
safety studies to assess the drug’s long-term effects on
cholesterol levels and liver function. Boehringer Ingelheim is hoping for
European approval for their drug later this year.
Efavirenz and statin interaction
The non-nucleoside efavirenz considerably lowers levels of three commonly
used anti-lipid drugs, a US study has found. The US Aids Clinical Trials Group
found efavirenz lowered levels of simvastatin, atorvastatin and pravastatin;
statins commonly used to reduce high cholesterol. However, they found statins
had no effect on efavirenz levels. If you are taking efavirenz with one of
these drugs, speak to your doctor about whether to increase your statin dose.
HIV drugs do not further damage liver in co-infected
Antiretroviral therapy rarely increases liver enzymes significantly
in people co-infected with HIV and hepatitis C. Researchers re-visited the
medical notes of 85 co-infected patients who were
followed for at least one year after starting HAART. They found even where
people had elevated liver enzymes, they were not associated with liver-related
side effects. These people were no more likely to experience opportunistic
infections or death than those whose liver function was normal.
Capravirine development halted Pfizer, the world’s largest
pharmaceutical company, has terminated trials of its non-nucleoside,
capravirine. Until recently, treatment activists had hoped capravirine would
provide another treatment option for people who experienced failure on the
non-nucleosides (NNRTIs) efavirenz or nevirapine. The trials were halted after
data showed the drug was no more effective than a placebo when given alongside
the
protease inhibitor nelfinavir to people resistant to NNRTIs.
Novel HIV drug to be tested
A pipeline drug that uses a novel way of preventing HIV from hijacking
human cells is to be studied in people living with HIV for the first time.
Patient enrolment for a trial of the oral HIV integrase inhibitor GS 9137
has already begun in the US. The trial will look at the safety, tolerability
and effectiveness of the new drug. Integrase is an enzyme which HIV uses to
integrate its genetic material into the DNA of human cells. GS 9137 would
block this process. No integrase inhibitor is currently licensed, but several
companies have them in early development.
Switch to atazanavir improves lipids
People with increased blood fats such as cholesterol or triglycerides
after treatment with
protease inhibitors may benefit by switching to the newer PI, atazanavir.
A small German study of 33 people with severely raised blood fats showed that
switching to atazanavir led to a 46 per cent reduction in triglycerides and
an 18 per cent reduction in total cholesterol after 24 weeks. Triglycerides
began to rise again by week 48 but total cholesterol remained down.
Clearly, switching to atazanavir may be of benefit to you if you have elevated
lipid levels. What is still not clear is whether these decreases in lipid
levels will lead to fewer heart attacks.
