Compiled by Robert Fieldhouse
New US guidelines suggest earlier T-20
use
The US Department of Health and Human Services has updated its HIV treatment
guidelines on
prescribing T-20. The department now supports use of the fusion inhibitor
T-20 (Enfuvurtide) with an active ritonavir-boosted protease inhibitor (PI)
in people who have experienced treatment failure with three different classes
of drug. The department argues this strategy results in better and more prolonged
suppression of HIV.
Dr William Powderly, of University College Dublin, said: “In three class
experienced patients, the use of the fusion inhibitor T-20 with an active
boosted PI with demonstrated activity against PI-resistant virus should be
the foundation of the new regimen.” Previously the guidelines emphasised
preservation of immune function and delay of clinical progression as treatment
goals for people with extensive prior treatment and drug resistance.
Now, with the emergence of new active boosted PIs such as tipranavir or TMC-125
to pair with T-20, the updated guidelines stress viral load suppression should
be the goal of therapy even when someone is highly treatment-experienced.
http://aidsinfo.nih.gov/guidelines
Study backs tests to avert drug failure
Monitoring levels of HIV drugs in the blood may help doctors tailor dosing
to minimise risk of side effects or head off virological failure, a new study
suggests. Therapeutic drug level monitoring (TDM) can help doctors establish
whether protease inhibitors are present in sufficient quantities or detect
whether NNRTIs have reached toxic levels. Doctors at Madrid’s Carlos
III Hospital looked back at every request for TDM made for people living with
HIV between October 2000 and August 2003. The hospital measured the lowest
concentrations in samples collected just before the morning dose was due to
be taken. The analysis included 151 samples from 137 people. They found doctors
tended to request drug level checks because of side effects (in 59 per cent
of requests) and less often for virologic failure (39 per cent) or for suspected
drug interactions
(2 per cent). They typically ordered NNRTI level monitoring because of side
effects and protease inhibitor monitoring because of treatment failure. TDM
confirmed high antiretroviral concentrations in 36 per cent of patients with
suspected drug toxicity and low concentrations in 37 per cent with poor virologic
responses.
Using TDM results, doctors modified NNRTI or protease inhibitor doses in 37
per cent of patients. Dose changes helped 80 per cent of these people achieve
target drug concentrations. Follow-up TDM showed 79 per cent maintained target
drug levels.Researchers concluded: “[TDM] may be a useful tool to identify
toxic levels of NNRTIs and subtherapeutic concentrations of protease inhibitors.”
HIV Medicine 2005; 6:360-365.
Tipranavir licensed in Europe
Boehringer Ingelheim’s novel protease inhibitor tipranavir (Aptivus)
received European approval on 25 October. The drug, a non-peptidic protease
inhibitor (PI), is taken as two tablets twice-daily alongside two ritonavir
capsules, in combination with other HIV drugs, in people with previous experience
of HIV therapy who have HIV resistant to other PIs. Regulatory approval was
granted on the basis of the results of clinical trials including over 1,400
treatment-experienced individuals. People who received tipranavir were more
likely than individuals taking a comparator protease inhibitor to achieve
a response to treatment. Professor Margaret Johnson (above), of London’s
Royal Free Hospital said: “Tipranavir is a significant breakthrough
for the many patients who have been on HIV therapy and are in need of powerful
new treatment options to help manage their illness.” The most commonly
reported side effects of tipranavir are similar to those seen with other boosted
PIs and include diarrhoea, nausea, fatigue, headache and vomiting.
Red-eyed frogs: a leap forward?
Researchers have found a chemical in the skin of Australia’s red-eyed
tree frog that can block HIV infection by destroying HIV particles. They hope
the find may lead to the development of a lotion which could be used by HIV
negative people before sex, or by HIV positive women to prevent transmission
to their partner.
Journal of Virology, October 2005
HIV damages the brain despite ARVs
New
research suggests our brain remains vulnerable to infection even when people
receive highly active antiretroviral therapy. US researchers compared three
dimensional MRI (magnetic resonance imaging) brain scans of 26 people with
Aids with those of 14 who were HIV negative. They found those with Aids had
up to a 15 per cent tissue loss in regions of the brain which regulate movement
and co-ordination. Use of antiretroviral therapy did not reduce the tissue
loss. The remaining three-quarters of the brain was unaffected. Specific patterns
of tissue loss correlated with physical and mental symptoms including impaired
motor co-ordination and slowed reflexes. The team of researchers also suggested
that loss of T-cells from the immune system may contribute to thinning of
the brain’s language cortex and reasoning centre. This may illuminate
why some people with advanced HIV develop mild vocabulary loss which can worsen
into memory loss and dementia similar to the symptoms of Alzheimer’s.
A protective blood barrier prevents many HIV drugs from entering the brain,
leaving it as a reservoir where HIV can multiply. Some drugs such as AZT and
abacavir have been shown to cross this barrier and reduce HIV replication
in the brain. The researchers suggest that brain scans should be used to test
the ability of new drugs to penetrate the brain during trials.
Many in UK denied resistance testing
A significant proportion of people who experience virological failure on HIV
therapy are not
getting resistance tests to guide their choice of a new combo, a new audit
has revealed.
One in four patients switching HIV therapy because their drugs are no longer
suppressing the virus are not offered the key test before switching, according
to the latest British HIV Association (BHIVA) audit of clinical practice at
UK HIV clinics. A total of 134 clinics participated in the audit, providing
data on 504 patients. Findings were presented to the autumn BHIVA conference
by Elizabeth Hart of North Manchester General Hospital.
BHIVA has clear recommendations about when a resistance test should be offered.
In particular, testing for transmitted resistance is recommended in all newly
diagnosed patients who present with either acute seroconversion or established
infection. Testing for transmitted drug resistance is recommended before starting
therapy. If you are on therapy that is failing, resistance testing should
be undertaken when your viral load reaches 1,000 copies while you are still
on treatment.
Chris O’Connor reports from the 2005 European sessions of the International Association of Physicians in Aids Care (IAPAC), in Amsterdam
Mandatory HIV testing of migrants came under fire at the 2005 European sessions of the International Association of Physicians in Aids Care. Dr Mark Nelson, of Chelsea & Westminster Hospital, London, said: “More and more countries are imposing HIV antibody testing, not just as a pre-departure requirement, but also on arrival. HIV tests are being carried out without consent and counselling, without any strategic planning of support mechanisms and with no confidentiality.” Most recently, Iraq introduced compulsory testing of all people entering the country from Syria. With international migration in 2002 put at 185 million migrants worldwide, and forecast to rise to 230 million by 2050, human mobility had impacted on the spread of Aids. Other strategies, apart from mandatory testing, have to be found to cope with HIV infection, he added. Studies on mobile populations are scarce but it’s known that the spread of HIV in Uganda was linked to cross-border truckers and migration. Migration between low and high HIV prevalence countries such as Laos to Thailand and Nepal to India has also been a factor. Mobile populations have been shown to be three times more likely to be infected with HIV than non-mobile groups.Dr Nelson said the solution is to make mobile populations a primary focus of Aids response work and improve access to education and treatment together as well as managing irregular migration better.Trafficking of people for sexual exploitation and the human rights of migrants also need addressing Dr Nelson presented figures from the UK’s Health Protection Agency that showing migrants have more advanced disease at HIV diagnosis compared to the general population. 20 per cent of gay men at diagnosis had CD4 counts below 200 at diagnosis while 40 per cent of heterosexual (mainly migrant) men and women had CD4 counts below 200 at diagnosis.He added that individualisation of type of care and disease care was “paramount” as was the creation of family clinics to address the specific needs of migrants.
Doctors are now questioning the wisdom of changing HIV therapy in people with
raised lipids, according to a leading Dutch HIV physician.Dr Peter Reiss,
associate professor with the Academic Medical Centre in Amsterdam, said findings
from a recently published Italian study on controlling lipids in people with
HIV had forced clinicians to think again.The study, published in the journal
Aids, found that HIV positive patients with raised lipid levels could benefit
more by adding the lipid-lowering drugs, pravastatin or bezafibrate, than
switching their regime to the NNRTIs nevirapine of efavirenz. In the study,
130 patients were evaluated over 12 months.
Part of the group switched from their protease inhibitor (PI) containing regimen
to nevirapine or efavirenz. These groups showed reductions in triglyceride
levels of 25 per cent and of 9.4 per cent respectively.
However, patients who remained on their PI-based regime and were given pravastatin
or bezafibrate saw triglyceride reductions of 41 per cent and 46 per cent
respectively. Similar patterns were observed for total and LDL ‘bad’ cholesterol. Speaking at the 2005 sessions of the IAPAC in Amsterdam,
Dr Reiss said: “The findings of this study surprised a lot of clinicians.”
Reiss also described as “very promising” two studies, which reported
reductions in triglyceride levels of around 25 per cent in people on antiretroviral
medication who took Omega-3 fish oils (polyunsaturated
fatty acids).
• Aids 19:1051-1058, 2005
• Clini Infec Dis 41, 2005
• CROI, 12, abstract 39
A delegate called for more research into the use of the corticosteroid prednisolone,
often used as an anti-inflammatory for asthma and arthritis, to slow falls
in CD4 counts during treatment interruptions.
Dr Albrecht Ulmer, from Stuttgart, first presented his study at the World
Aids Conference in Bangkok in 2004. Ulmer told the conference: “It’s
an inexpensive generic so there is no incentive to conduct any studies.”
His studies with low dose prednisolone (5mg) showed stable CD4 levels compared
to dropping levels in patients who stopped all therapy. Side effects included
weight gain and minor gastrointestinal problems. It’s also known to
HIV doctors that chronic corticosteroid use can lead to immune suppression.
For expert commentary on the study, visit The Body at www.thebody.com/confs/aids2004/pierone1.html
Hepatitis B (HBV) is the next big issue facing clinicians in hepatitis and
HIV co-infection, the conference heard.
Stefan Mauss, of the Centre for HIV and Hepato-gastroenterology in Düsseldorf,
said: “Hep B is now a bigger killer than hep C.” Worldwide, several
million people are estimated to be co-infected with hepatitis and HIV. Unlike
for hepatitis C, there is a vaccine against HVB, but data on the efficacy
of drugs in people co-infected with HIV and hep B is still very limited. New
hep B drugs should be available in 2006 including entecavir, clevudine, telbivudine.
Journal of Hepatology 42, 2005
CCR5 trials abandoned
GlaxoSmithKline (GSK) has stopped trials of its CCR5 inhibitor, aplaviroc,
after encountering additional cases of liver abnormalities in patients. Earlier
this year, GSK stopped a trial of aplaviroc in patients who had not received
prior treatment for HIV after two cases of severe liver toxicity. Meanwhile,
Schering Plough has announced it has halted trials of its experimental CCR5
inhibitor vicriviroc, in people new to HIV treatment amid concerns of early
viral load rebound. Its study in treatment-experienced patients will continue,
the company said.
Latest BHIVA guidelines state that “the cost of the regimen should also be considered” when choosing therapy. Over half of the clinics (54 per cent) that took part in the latest BHIVA audit said they took cost into account when choosing therapy while 44 per cent said that cost was not a consideration.
Women co-infected with HIV and hepatitis C (HCV) have detectable HCV in their
vaginal secretions more often than women infected with HCV only. US researchers
measured cervicovaginal HCV viral load in 58 co-infected women and 13 women
with HCV only. None of the HCV-only group had detectable HCV in cervicovaginal
fluid, but detectable HCV was found in 18 (29 per cent) of the co-infected
women. HCV detection in the vagina did not correlate with CD4 cell counts,
HIV viral load in blood or antiretroviral therapy.
Journal of Infectious Diseases 2005; 192:1557-1565.
US researchers who followed 571 women for 12 months have concluded that HIV
infection and low CD4 count predict earlier menopause. Fifty-three per cent
of the women were HIV positive and the average age was 43. Of the 102 women
who experienced menopause during the study, 62 were HIV positive with an average
age of 46, while 40 were HIV negative with an average age of 47. A CD4 count
above 500 in women with HIV reduced the chance of menopause by 80 per cent.“Whether
early onset of menopause in HIV-infected women increases their risk of osteoporosis
and heart disease requires further study,” the authors concluded.
Clinical Infectious Diseases 2005; 41:1517-1524.
New research focusing on men and women on treatment suggests lower pretreatment
CD4 counts and higher viral load predict both trunk and limb fat abnormalities.In
men, a higher pretreatment CD4 count correlated with increased arm and leg
fat (1.8 per cent average annual increase per 100 cells).
Treatment with AZT correlated with a 10.8 per cent loss of trunk fat and a
4.9 per cent loss of limb fat per year. Interestingly, use of d4T did not
correlate with fat loss. ARV therapy predicted a 1.6 per cent loss of arm
and leg bone mineral density annually, protease inhibitor therapy a 1.9 per
cent drop, and AZT a 2.6 per cent yearly decline in trunk bone mineral content.
Clinical Infectious Diseases 2005; 41:1662-1670.
