Compiled by Robert Fieldhouse
Treatment breaks back on agenda
Scheduled treatment interruptions are safe as long as people’s CD4 counts
remain above 350 cells, according to new research.
Earlier this year a similar trial, the SMART study, was abruptly halted after
participants on treatment breaks experienced a “worrying” number
of Aids events. At the time, experts predicted the end of interuptions as
a treatment strategy.
But now the Staccato study, involving 430 people, has found interuptions are
safe if people resume HAART if their CD4 count falls below 350.
In this study, patients could interrupt therapy again after their CD4 counts
rose above 350 for at least 12 weeks. In the SMART trial, patients only went
back on treatment when their CD4 count fell to 250.
Lead researcher Dr Bernard Hirschel said it was wrong to conclude the SMART
trial meant the end of all HIV treatment interruptions.
“In the SMART trial, the median interval between starting HAART and
starting the break was six years, but it was only about 18 months in Staccato
which is a massive difference.”
Around a third on the Staccato trial did not need to start therapy again after
22 months, but some had many stop/start cycles.
At the end of treatment only 7.7 per cent of subjects in the control group
and 6.8 per cent in the interruption group had viral loads below 500 copies.
Seven patients in the interruption group and three in the continued treatment
group developed drug resistance.
Seventeen patients experienced symptoms such as fever, sore throat or skin
lesions during their first treatment interruption, suggesting acute retroviral
syndrome, but only six had viral loads greater than 100,000 and there were
no Aids-defining events.
Lancet 2006; 368: 459-465
Kidney disease increases
As people with HIV live longer, kidney disease associated with HIV infection
or its treatment is becoming more common. Researchers from the University
of Munich reviewed cases of kidney disease associated with HIV since combination
therapy was introduced.
Acute renal failure is associated with advanced HIV infection, hepatitis C
co-infection and a history of antiretroviral treatment. Chronic kidney disease
is also common in people living with HIV.
Metabolic changes associated with antiretroviral therapy can contribute to
kidney disease by increasing the likelihood of diabetes and hypertension.
Toxic drug effects have also led to acute kidney failure, tubular necrosis
and kidney stones.
The researchers called for larger trials to evaluate the effect of different
drugs and urged doctors to be aware of the need to alter drug doses for people
with kidney impairment.
Clin Infect Dis 2006; 42: 1488-1495
Research to eradicate virus from body gets
cash boost
The US Foundation for Aids Research (amfAR) has awarded 12 grants and fellowships
to investigate eradicating HIV from the body.
The awards total almost $1.5 million and will fund scientific studies that
may reveal how to eliminate the virus altogether.
Many consider research focused on viral reservoirs, latent virus and acute
HIV infection to be the first step toward the elusive cure for HIV infection.
Research that led to highly active antiretroviral therapy (HAART) in 1996
remains one of the key scientific success stories in the 25-year-old epidemic.
But although HAART prolongs life by suppressing viral reproduction, reservoirs
of latent virus remain throughout the body. Because these reservoirs are beyond
the reach of HAART, it creates an impediment to eliminating HIV from the body
altogether.
amfAR is one of the world’s leading non-profit organisations supporting
HIV research, prevention, treatment and education.
Positive pregnant women prone to anaemia
and hypertension
Women living with HIV are more likely to have anaemia and high blood pressure
during pregnancy. They are also more likely to give birth to babies of lower
birth weight and with retarded growth than HIV negative women.
South African researchers reviewed the maternal and neonatal outcomes of 212
HIV positive and 101 matched HIV negative women. More than a quarter of pregnant
women in South Africa are HIV positive.
The HIV positive group had lower haemoglobin levels (10.85 vs 11.48g/dL),
weighed less (72.07 vs 76.69kg) and were more likely to present with abnormal
vaginal discharge (33 vs 25 per cent).
J Clin Nursing 2006; 15: 735-741
Dairy-free advice flawed
Eating
moderate quantities of dairy foods does not make HIV-related diarrhoea worse,
a new study has found.
Chronic diarrhoea is common among people with HIV in the HAART era and people
are often urged to avoid products containing lactose. But there is little
evidence to support this dietary strategy.
In a study of 49 HIV positive people with diarrhoea, researchers compared
stool weight in the eight hours following drinking low-fat milk (12g of lactose)
or lactose-free milk. Lactose was considered not to have had a harmful effect
if the stool weight did not differ by more than 167g in those that drank the
low fat milk. All but one participant was male and the average age was 42.
The average CD4 count was 390 and average viral load was 112 copies. Thirty-nine
were taking HAART.
Use of the lactose-containing milk was associated with a slight decrease in
stool weight from 167.6g to 126.3g. There was also a slight increase in stool
weight among those drinking the lactose-free milk.
“Given the risks of malnutrition and osteopenia in this population,
practitioners may wish to encourage their HIV patients with diarrhoea to include
moderate quantities of dairy products in their diets,” the authors concluded.
Arch Intern Med 2006; 166: 1178-1183
Oral entry inhibitor trials recruit
A drug that prevents HIV entering cells and can be taken orally is making
its way through late-stage clinical trials.
Currently the only entry inhibitor licensed for use in Europe is T-20, which
has to be injected. A new double-blind trial for the drug, known as SP01A,
is due to enrol 411 patients (137 placebo and 274 active dose) and study these
participants over 48 weeks. Double-blind means neither the patient nor the
researcher knows if the participant is receiving the drug.
The trial will also assess the safety and efficacy of SP01A on viral load
in treatment-experienced individuals. Results from the trial are expected
next year.
HIV therapy fails to fully restore gut immune
function
According
to latest research, HIV treatment fails to completely restore immune function
in the gut lining. Researchers at the University of California say this is
one way HIV can evade the effects of HAART, providing a reservoir where it
can hide and continue to replicate.
They looked at biopsy samples from 10 people living with HIV before starting
HAART and three years after. Comparing the samples, they evaluated HIV suppression,
CD4 cell restoration, HIV-specific CD8 responses and antiviral immune responses.
Three patients started HAART during primary (early) infection, while seven
started therapy during chronic infection.
Starting HIV therapy during primary HIV infection led to a more rapid and
sustained suppression of HIV in blood and in gut- associated lymphoid tissue
(GALT) than staring HAART during chronic HIV infection.
Restoration of gut mucosal CD4 cells was slow in people treated in both primary
and chronic HIV infection. None of the patients in the chronic infection group
was able to restore mucosal CD4 cells to normal levels by using antiretroviral
treatment.
Increased levels of HIV-specific CD8 cell responses also suggested incomplete
suppression of viral replication in GALT.
The findings show incomplete HIV suppression and increased immune activation
and inflammation in gut tissue in people on therapy predicts a slow and incomplete
restoration of the gut mucosal immune system.
Starting therapy before a severe loss of CD4 cells may help restore and maintain
both mucosal and peripheral blood immune systems.
J Virol 2006; 80: 8236-8247
New PI licensed in United States
A new protease inhibitor, Prezista (TMC114), developed to treat resistant
strains of HIV in combination with other medications, has won US approval.
TMC114 is given alongside a low dose of ritonavir, an older protease inhibitor
which slows clearance of the new drug from the body and increases its concentration.
US activists welcomed the price of new drug, which manufacturer Johnson &
Johnson has pegged at around the same price as the older PI atazanavir. This
makes it cheaper than its main competitor tipranavir.
Any new antiretroviral drug needs to be partnered with another fully active
drug to increase the likelihood of an effective long-term response.
Roche Pharmaceuticals has also announced that, in clinical trials, two-thirds
of patients resistant to other medications who combined its drug T-20 with
TMC114 achieved an undetectable viral load. Side effects of TMC114 can include
diarrhoea, nausea and headache as well as mild to serious skin rashes.
TMC114 is the first of three promising drugs being developed by Johnson and
Johnson to receive a license. It is expected to be followed by TMC125, an
NNRTI likely to be launched in late 2008 and TMC278, a second non-nucleoside
reverse transcriptase inhibitor.
Three-in-one once daily drug approved in
USA
The US Food and Drug Administration has granted approval for the first ever
fixed-dose combination of three widely used HIV drugs.
Atripla, as it is called in the US, is a once-daily single-tablet regimen
for treating HIV. It can be used as a stand-alone therapy or in combination
with other antiretrovirals.
The tablet contains 600mg of efavirenz (Sustiva), 200mg emtricitabine/FTC
(Emtriva) and 300 mg of tenofovir (Viread).
It can replace the frequently prescribed first-line combination of Sustiva
(600mg of efavirenz) and the fixed-dose tablet Truvada (200mg emtricitabine/300mg
tenofovir).
A clinical trial called GS 934 showed the three drugs were better tolerated
and resulted in a superior treatment outcome over 48 weeks when compared to
the previous gold standard of AZT, 3TC and efavirenz. A 96-week analysis was
due to be presented at the World Aids Conference in Toronto.
Significantly, this marks the first ever collaboration of two pharmaceutical
companies, Gilead Sciences and Bristol-Myers Squibb, to combine their separate
drugs in a single fixed-dose combination. EU approval for the new pill is
expected in the coming year.
Exercise trims waists in women with lipo
Women
living with HIV can become stronger, fitter and trimmer by following a supervised,
home-based aerobic and resistance training programme, according to latest
research.
Research led by Dr Steven K Grinspoon evaluated the effects of a 16-week course
in 40 women living with HIV.
Before starting the women had seen a thickening of their waists and reported
body fat changes related to lipodystrophy.
After 16 weeks their aerobic capacity and endurance increased while these
decreased in the control group, the authors report.
Women in the exercise group were found to be stronger all round than in the
control group and their waists became smaller. But there were no differences
in abdominal or total fat between the groups.
The researcher concluded: “The programme made patients feel better about
their health, which may improve [treatment] compliance as well.”
Arch Intern Med 2006;166:1225-1231.
EU approves new ‘easy’ lopinavir
pill
The European Commission has approved a new easier to take formulation of Abbott’s
protease inhibitor lopinavir/ritonavir (Kaletra). The new formulation was
approved in the US last October. Adults taking lopinavir/ritonavir can now
take the pill with or without food and the number of daily pills is down from
six to four.
Now EU approval has been secured, Abbott can seek approval for the drug in
developing countries where keeping drugs refrigerated can be a problem.
HAART fails to cut risk of death in first
year
Although far fewer people progress to Aids and death these days, there
has been no corresponding drop in the risk of people dying in the 12 months
after starting HIV therapy.
In fact researchers at Bristol University found people who began HAART in
2002/3 were more likely to progress to Aids in the first year than those who
started therapy in 1998. This was despite having lower viral loads.
TB infection and late diagnosis in a growing number of heterosexuals and women
may go some way to explain the discordant findings, the researchers said.
The data came from 12 cohort studies involving 22,217 people in Europe and
North America who began HAART between 1995 and 2003. During that time heterosexual
infections rose from 20 to 47 per cent and the number of female patients doubled
from 16 to 32 per cent. CD4 count on starting HAART climbed from 170 in 1995/6
to 269 in 1998, but had fallen to 200 in 2002/3.
HIV suppression with medication improved during the study period. In 1995/6,
just over half of patients achieved a viral load of 500 or less within six
months of starting HAART. By 2002/3, this had increased to 83 per cent.
However, overall the risk of death within one year of starting HAART remained
fairly stable during the nine-year period.
Lancet 2006;368:427-428,451-458.
US approves HPV vaccine
The
US has approved the first vaccine to prevent the virus that can cause cervical
cancer.
Public health experts dubbed Gardasil a major advance against a disease that
annually kills around 300,000 women worldwide.
Given in three doses over six months, Gardasil targets four HPV (human papilloma
virus) types believed to cause more than 70 per cent of cervical cancer cases
and 90 per cent of genital warts. The vaccine was approved for use in girls
and women aged nine to 26.
GlaxoSmithKline applied for EU approval of their HPV vaccine, Cervarix, back
in March this year.
Brain bleeds linked to new PI
Thirteen
people have experienced bleeding in the brain, and eight of these have died,
after taking the new protease inhibitor tipranavir, the US Food and Drug Administration
reports. Fourteen intracranial haemorrhages occurred in 13 of the 6,840 HIV
positive people taking part in tipranavir clinical studies.
The drug was licensed last year to treat protease inhibitor-resistant HIV
in combination with twice-daily ritonavir. Manufacturer Boehringer Ingelheim
(BI) issued a letter notifying healthcare professionals of the findings.
BI told doctors it was confident of tipranavir’s benefits in patients
“within its labeled indication” (those patients with drug resistance)
and that no intracranial haemorrhages have been seen in patients taking tipranavir
following licensing.
Many patients who experienced an intracranial haemorrhage had additional medical
conditions such as head trauma and recent neurosurgery. Many were also taking
other medications, including anticoagulant and antiplatlet drugs, which may
have played a part in the intracranial bleedings.
Meanwhile, BI has halted study of tipranavir in people using protease inhibitors
for the first time because patients receiving a 500mg dose of tripranivir
with 100mg of ritonavir had inferior viral load outcomes when compared to
patients receiving lopinavir/ritonavir (Kaletra).
