Robert Fieldhouse reports from the 12th Annual British HIV
Association Conference, Brighton
New herpes virus discovery linked to KS
Researchers
in the States have identified a human cell surface molecule that plays a critical
role in infection by Kaposi’s sarcoma herpes virus (KSHV).
KSHV causes some lymphoma and Kaposi’s sarcoma (KS), a major cancer
associated with HIV that manifests as multiple purple-coloured skin lesions.
Discovery of the surface molecule called xCT may lead to new ways of treating
KSHV and enable scientists to determine if levels of xCT affect disease severity.
Although less common in the developed world than in the early years of Aids,
KS is still the commonest cancer associated with HIV.
People with HIV are 354 times more likely to develop KS than HIV negative
people. It may also explain why certain groups are more at risk of getting
KS.
Researchers at the National Institute of Allergy and Infectious Disease at
the US National Institutes of Health found that xCT was a major gateway used
by KSHV uses to enter human cells. It may also play a role in the development
of KS. Its natural function in the body is to transport molecules into cells
that are needed for protection against stress. When cells are stressed, they
express more of this molecule on their surfaces. First identified by a Hungarian
doctor, Moritz Kaposi, in 1872, KS was considered rare, usually only occurring
in older Italian men, transplant patients and young men in certain parts of
sub-Saharan Africa.
It’s now 25 years since the first recorded cases of KS lesions appearing
in young American gay men (subsequently found to be HIV positive).
Science DOI: 10.1126/science.1120878 (2006)
Promising new nuke hits buffers
Development of the once-daily nuke (nucleoside analogue) Reverset has been
terminated due to concerns about its potential effect on the pancreas.
Researchers stopped the study after they detected an unacceptably high rate
of grade 4hyperlipasaemia.
Hyperlipasaemia is the name given for the presence of the enzyme lipase in
the blood and may be a sign of pancreas damage.
Reverset was one of the most promising drugs in the next generation of nukes.
It appeared to show good activity after the failure of both AZT and d4T as
well as 3TC and FTC.
Lung cancer risk higher in HIV positive
People living with HIV appear to be at greater risk of getting lung cancer,
even if they are non-smokers, research suggests. And the extent of a person’s
immune system damage seems to have no bearing on the risk.
Researchers analysed 5,238 HIV positive people attending Baltimore clinics
between 1989 and 2003. Lung cancer rates in this group were compared to a
group of HIV negative people.
Thirty-three lung cancers occurred in the study group. Being older was identified
as a risk factor for lung cancer, but gender, race, and CD4 cell count appeared
to have no effect. Almost 70 per cent of the people with HIV in the cohort
smoked. But even non-smokers in the group were still more likely to develop
lung cancer than HIV negative people.
“As people with HIV live longer, lung cancer will likely grow in importance
as a cause of morbidity and mortality,” the authors concluded.
“Clinicians should be alert to the possible diagnosis of lung cancer
in HIV-infected patients,” they added.
Journal of Clinical Oncology 2006; 24: 1383-1388
Positive people do well after heart treatments
A procedure that unblocks narrowed arteries without surgery is an effective
way to restore blood flow to the heart in people with HIV, new research suggests.
This study is interesting as little research has been done on the impact of
coronary procedures in people living with HIV. French researchers observed
100 people (50 with HIV, 50 without) who underwent percutaneous coronary intervention
(PCI), for conditions like heart attack and angina.
After an average of 20 months, 80 per cent of people living with HIV and 84
per cent of HIV negative patients had no major adverse cardiovascular events.
The heart attack rate was eight per cent in HIV positive people and zero in
HIV negative patients.
The researchers said further study was warranted on long-term prognosis of
acute coronary syndrome and coronary revascularization and, in particular,
use of drug-eluting stents in patients with HIV.
Heart 2006; 92: 543-544
Hope for HIV-related brain damage
Valproic acid is a safe and well tolerated treatment for HIV-associated cognitive
impairment, a pilot study has found.HIV-related cognitive impairment is associated
with disease progression, and symptoms include forgetfulness, clumsiness,
concentration problems, language difficulties and mood swings.
Currently there is no treatment for HIV-associated cognitive impairment beyond
optimised antiretroviral therapy.
And given cognitive problems can still occur in people whose HIV is well controlled,
other forms of treatment are needed. The study found valproic acid had a neuro-protective
effect with a trend towards improved neuropsychological performance in people
with HIV when compared with those on placebo.
Researchers randomised 22 people living with HIV, six of who had cognitive
impairment, to receive 250mg of valproic acid twice-daily or placebo for ten
weeks. Patients underwent neuropsychological evaluations at the start and
at six and ten weeks, as well as assessments of fatigue, overall function
and depression. They also had a brain scan at the start and after ten weeks.
Valproic acid had no ill effect on CD4 counts or viral load. A one-year study
is now planned.
Neurology 2006; 66: 919-921
New vaccine study recruiting
Volunteers in the US are signing up for an experimental HIV vaccine developed
at Atlanta’s Emory University. Only 12 people are expected to take part.
HIV negative volunteers are given low vaccine doses to check for safety and
how their immune system responds.
A second, higher-dose trial, with up to 36 people, is expected to begin in
a few months. The GeoVax product is one of more than 30 preventive HIV vaccines
in early stages of clinical trials, according to the International Aids Vaccine
Initiative.
One of the furthest along is a Merck vaccine, which tries to build immunity
using a modified cold virus. About 3,000 people are being enrolled in Merck’s
phase two trial of this vaccine.
GeoVax vaccine is administered in four doses, spread over the course of about
two months. The first two doses contain fragments of HIV’s genetic information
(DNA), which prime the patient’s immune response system. The second
two doses contain an altered poxvirus designed to boost the immune system.
Emory researchers began working on this vaccine back in 1997.
In 2003 and 2004, the DNA component of the vaccine was tested in 30 HIV-negative
volunteers in three sites in the US. It was deemed safe. The new trials are
testing both these components together.
Associated Press
HIV increases risk of ‘brittle bones’
in middle-aged women
Middle-aged
women living with HIV have lower bone mineral density (BMD) compared with
their HIV negative peers, latest research suggests.
Several studies have reported increased prevalence of reduced BMD (osteopenia
and osteoporosis) among people living with HIV.
These new findings suggest that a decrease in bone density can be linked to
HIV itself, independently of the drug combination women are taking.
Researchers evaluated bone mineral density in 495 middle-aged women, half
of who (263) were HIV positive. They chose participants with similar lifestyles
including physical activity, cigarette smoking and alcohol and opiate use
to reduce potential biases.
Twenty-three per cent of all participants had low BDM, mostly osteopenia (only
three per cent had osteoporosis). Low BDM was more common in women with HIV
(27 per cent) compared with HIV negative women (19 per cent).
Use of antiretrovirals did not seem to affect BMD. Other factors independently
associated with lower BMD in both groups were older age, being caucasian and
weighing less.
Clinical Infectious Diseases 2006; 42: 1014-1020
HIV with hep C affects survival rates
People coinfected with HIV and hepatitis C have slightly worse survival rates
than people infected with HIV alone, according to new research among people
on salvage therapy.
Researchers from the OPTIMA (Options in Management with Antiretrovirals) study
evaluated different treatment approaches for people with limited options in
the US, Canada and UK. They looked at the effect of hepatitis C on the rate
of new Aids cases and survival in study participants.
Of 311 people included in the analysis, 72 (23 per cent) were coinfected with
hepatitis C. Over an average of two years, one in four people coinfected with
hep C died compared with one in six people infected with HIV only.
Researchers found that three quarters of co-infected people reported injecting
drug use
compared with only one in four people who were infected with HIV alone.
People only infected with HIV lasted longer on their first OPTIMA combination,
on average seven months, compared to four months among people coinfected.
Researchers concluded: “Co-infection with hepatitis C appears to increase
the risk of mortality, but this effect might be partly explained by a shorter
time to switching/ stopping antiretroviral therapy.
“One possible reason could be that patients infected with hepatitis
C are less able to tolerate antiretrovirals.”
Abstract O1533
Solo boosted PI therapy proves potent for
some
A majority of highly treatment- experienced people switched from a standard
multiple drug combo to lopinavir-ritonavir (Kaletra) achieved an undetectable
viral load for over a year, a small study has shown.
Researchers led by Dr Laura Waters at London’s Chelsea and Westminster
Hospital switched 35 people from their existing regimen to the ritonavir-boosted
protease inhibitor lopinavir as part of their routine care.
Almost two-thirds of those switched to the simplified regime saw their viral
load go undetectable. Before switching, the average viral load was 55,000
and average CD4 248. All had previously used five ARV combos before switching.
Five people could not be followed-up and two quit due to side effects, leaving
28 people in the analysis. Half achieved a viral load below 50 copies and
saw an average CD4 increase of 115. Over a year, only eight participants switched
therapy: three due to virological failure, two because of viral load ‘blips,’
two for unknown reasons, and one because their CD4 declined.
Of the remaining 20 people, 12 (60 per cent) had an undetectable viral load
after an average of 14 months treatment with lopinavir-ritonavir alone.
Abstract P9
Almost one in ten HIV positive people have
hep C
A major study has reported that nine per cent of HIV positive people in UK
are coinfected with hepatitis C. The UK Collaborative HIV Cohort (UK CHIC)
collected data from seven HIV clinics that have treated some 21,250 patients
since 1996. Around half of those included in the cohort (11,357) had taken
at least one hepatitis C antibody test with 1,045 (9 per cent) testing hep
C positive.
For the past two years, British HIV Association treatment guidelines have
recommended that all people living with HIV are tested for hepatitis C virus
soon after HIV diagnosis and thereafter at regular intervals if they are deemed
at particular risk of acquiring the virus.
Associated risk factors include injecting drug use or unprotected, group or
rough sex.
The proportion of people with HIV also testing for hepatitis C has increased
over time: from just seven per cent in 1995 to 72 per cent in 2003.
Because testing is now widespread, the proportion of people testing hepatitis
C positive has actually fallen over time. In 1995, 26 per cent of the 369
people tested for hepatitis C antibodies were positive, falling to eight per
cent of the 8,033 people tested in 2004.
Abstract O14
First combo can last seven years
People living with HIV in the UK remain on their first antiretroviral combination
for an average of seven years, according to new research.
Between 1996 and 2002, 3,647 people living with HIV started their first triple
combination therapy at one of the 27 participating HIV clinics across the
UK.
As they began therapy for the first time, people’s CD4 counts averaged
270 and viral load 75,000 copies. Around one in ten had an Aids diagnosis
before starting therapy.
Their first therapy lasted an average of 6.7 years. People who started with
a CD4 count below 170 cells or with a prior Aids-defining illness, or who
started therapy with an unboosted protease inhibitor, stayed on their first
combo for a shorter time.
Researchers concluded that treatment failure and viral load rebound accounted
for between 40 and 50 per cent of treatment switches, and that side effects
were the main reason most people switched therapy.
Abstract O33
GPs fail to spot signs of HIV in undiagnosed
African people in London
Three out of four Africans newly diagnosed with HIV in London have
visited their GP in the two years prior to their HIV being picked up, often
with symptoms suggestive of HIV infection. African people in the UK typically
present for HIV treatment and care much later than caucasians.
Between 2004 and early 2006, investigators surveyed 236 recently diagnosed
Africans at 15 HIV centres in the capital. They were asked about their use
of primary care in the two years prior to HIV diagnosis. Almost three quarters
came from countries with an HIV prevalence of more than 15 per cent. Just
over half had a CD4 count below 200 at diagnosis, placing them in need of
immediate treatment.
People often went to their GP with
illnesses and symptoms such as chest complaints, flu-like symptoms and skin
problems that should have alerted the family doctor to the possibility of
HIV. GPs mentioned HIV testing to 16 per cent of the patients and just over
half took a test.
One in three said they had previously taken an HIV test, and a third of these
said they underwent the test in the UK. Investigators hypothesised that one
in five African people recently diagnosed with HIV had been infected with
the virus since arriving in the UK.
Dr Fiona Burns from London’s Mortimer Market Centre said lack of trust
in GP services was a potential barrier to accessing primary care. While 89
per cent said they trusted their HIV clinic staff, just 37 per cent said they
trusted their GP’s staff and only 30 per cent had disclosed their HIV
status to their GP.
Abstract O29
Global HIV strains found in UK’s gay
men
Around
three per cent of HIV infections acquired through sex between men in the last
five years were of non-B HIV subtypes.
Subtype B is the UK’s most prevalent HIV subtype. But migration patterns
have led to a rise in the prevalence of other subtypes historically found
in other parts of the world.
Between 2005-6, researchers from London’s Imperial College undertook
a prospective longitudinal study at a London HIV clinic of 135 UK-born gay
men who had recently seroconverted.
Five of these men (3 per cent) were found to have a non-B subtype. Over time
there was no change in the frequency of non-B subtype acquisition.
Nobody infected with a non-B
subtype had not acquired drug resistance from their partners.
Abstract O3
Clarification. Antacids fail to weaken new protease inhibitor tablet
Last month we reported how levels of the new tablet version of lopinavir-ritonavir
were not reduced by co-administration with the antacids omeprazole or ranitidine.
We mistakenly stated that the bioavailability of ritonavir-boosted atazanavir
was also unaffected co-administered with these antacids. This was not the
case: bioavailability of ritonavir-boosted atazanavir fell by 48 to 62 per
cent when co-administered with an acid-reducing drug. Abstract 578
