News (Updated October
2, 2011)
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27 Sep 2011
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IRIN
In 2009, researchers
released the results of a then unpublished Haitian clinical trial. Conducted
among 800 HIV patients, the study showed that those who received antiretrovirals
(ARVs) when their immune systems were stronger - at higher CD4 counts of 200 to
350 - were less likely to die than their peers who waited until their CD4 counts
fell to 200. [ http://www.plusnews.org/report.aspx?reportid=84791 ]
About five months later,
the World Health Organization (WHO) issued new HIV treatment guidelines that
advised countries to start HIV patients on treatment at a new higher CD4 count
of 350 instead of 200. [ http://www.plusnews.org/report.aspx?reportid=87263 ]
Now those researchers have
released the world's first and possibly only cost-effectiveness study on earlier
HIV treatment tied to a randomized clinical trial. Published in the September
2011 edition of the medical journal, PLoS Medicine, the study is based on data
from the original Haitian study that allowed researchers to calculate costs
associated with the first three years of earlier treatment - including
everything from drug and family caregiver costs to subsidies for patient
transport to and from the clinic. [ http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001095
]
Bruce Schackman, associate
professor of public health at the US Weill Cornell Medical College and a
co-author of the study, said this was probably the first and last research of
its kind. Given the overwhelming evidence for early treatment, duplicating the
study now would be unethical, he said.
"This was a unique
opportunity to do this kind of research," Schackman told IRIN/PlusNews.
"I don't think we'd be able to do a similar comparison [study] given the
compelling mortality gain we've seen with early treatment."
And although cost
effectiveness is relative, Schackman said he believed the findings were
applicable to other countries.
"The patterns of care
that occurred in the early treatment versus the standard treatment group are
generalizable," he told IRIN/PlusNews.
"Among the standard
treatment group, you see higher costs for lab tests and more costs for
outpatient care because patients were not yet receiving drugs and got
sicker."
He added that some
countries with higher healthcare costs than
With an HIV prevalence of
about 2 percent,
"This study is so
important because the
Koenig is also the medical
director for Partners in Health's
Long-term benefits
Up until now, the
cost-effectiveness of early treatment had only been shown through modelling
studies. These have demonstrated that while earlier treatment involves more
money for drugs initially, it becomes more cost-effective the longer patients
are on ARVs as they stay healthier for longer, decreasing the burden on national
health systems.
The median follow-up time
for patients enrolled in the
After the trial was
stopped in 2009, all patients with CD4 counts of 350 or below in the study were
offered HIV treatment and uptake was high, according to Koenig. However, those
patients who started treatment later may never recover as much of their immune
system as their early-treatment peers.
"There are
indications that patients who start treatment late never develop the immune
system that they would have with early treatment," she told IRIN/PlusNews.
"For the rest of their lives they are going to have more infections.
"For the price of two
Starbuck's lattes a month, you could preserve someone's immune system,"
Koenig added. "In the
Both authors said they
hoped their findings would help more developing countries move towards adopting
earlier treatment - and donors commit to supporting this.
"It's important to
highlight the findings of this study but also to continue the funding for early
treatment, which also has HIV prevention benefits that were not part of the
economic analysis, as well as direct life expectancy benefits," Schackman
said. "In this environment it's challenging to do that but we're hoping
this will provide the additional economic [rationale] to pursue this."
llg/kn/mw
The Daily Telegraph
reported that a “vaccine could reduce HIV to ‘minor infection’”. The
news story reports on a phase I clinical trial that assessed the safety of a new
HIV vaccine in a small group of people in
The researchers recruited
30 people who did not have HIV and gave 24 of them three injections of the new
HIV vaccine, which was based on a smallpox vaccine. The other six people
received placebo injections. The researchers followed the volunteers for 48
weeks.
The researchers found that
the vaccine appeared to be well-tolerated over this time and there were no
serious side effects. More than three-quarters of the volunteers had a
detectable immune response to the vaccine. However, the primary aim of this
preliminary study was to assess safety not effectiveness. It is not known
whether the immune response caused by the vaccine would be sufficient to protect
against HIV infection or to lower HIV levels in people who are already HIV
positive. It is likely that further safety trials in a larger group of people
will be performed before the effectiveness of this vaccine is assessed.
Where did the story come
from?
The study was carried out
by researchers from The Hospital Clinic-IDIBAPS,
The study was published in
the peer-reviewed medical journal Vaccine.
The research was covered
well by The Daily Telegraph, the Daily Mail and the Daily Mirror, which all said
that further tests would need to be carried out. The Daily Telegraph detailed
what the researchers had said the next steps would be.
What kind of research was
this?
This was a phase I
clinical trial to assess the safety of an HIV/AIDS vaccine and how well it could
provoke an immune response, which is a sign that a vaccine is having an effect.
Phase I studies are studies that test the preliminary safety of a treatment in a
small group of people. Often these types of studies do not have a control group.
In this case, there were 24 people who received the vaccine and six who received
a placebo. Importantly, this type of trial is not designed to test effectiveness
and the researchers were not trying to assess how well the vaccine would protect
people from contracting HIV. However, they did look at how strong the immune
response to the vaccine was. Immune response is a marker for eventual success of
the vaccine and a sign that the vaccine is having an effect.
The vaccine was based on a
smallpox vaccine that had been adapted with HIV genes. The vaccine was called
MVA-B. The idea was that the vaccine would prime the body to recognise HIV so
that it would mount a rapid immune response. If used to treat people who have
already contracted HIV, this would potentially allow the body to clear the HIV
to levels that don’t cause disease. If used to prevent people from getting
HIV, it would hopefully prevent the virus from entering cells in the first
place.
What did the research
involve?
The study was carried out
in
The 24 people received
three injections of the vaccine into their muscle, and the control group
received placebo injections. Both groups received these injections at the start
of the study, after four weeks and after 16 weeks. The participants were then
followed for 48 weeks.
The participants were
asked to use an effective method of contraception with their partner from 14
days prior to the first vaccination until four months after the last one.
The primary endpoints (the
measures considered to be most important by the researchers) were serious side
effects and how well the body mounted an immune response. They looked, in
particular, at a type of immune cell called a T-cell. The researchers also took
into account less severe side effects and how well the body produced antibodies
against the vaccine.
Screening for side effects
was performed throughout the study. Blood tests were performed at the study
start and at weeks four, eight, 16, 20 and 48. The participants were given safe
sex counselling and an HIV test at the screening interview and at weeks four, 16
and 48.
What were the basic
results?
The researchers said that,
overall, the vaccine was well-tolerated. A total of 169 adverse events were
reported during follow-up. Five of these were grade-three adverse events, which
would be considered serious. However, although the five serious adverse events
were all in the vaccination group, these were not considered to be related to
the study drug. For example, one volunteer had tonsillitis, one volunteer had a
traffic accident, one volunteer had both pneumonia and two asthmatic attacks. Of
the 145 reported milder adverse events (grade one and two), 52 were considered
to be definitely related to the vaccination. The most common mild adverse events
were pain at the site of the injection and headaches.
The researchers found that
positive T-cell immune responses were detected in 75% of volunteers and that
these were maintained until week 48 in 68% of the participants. The proportion
of responders increased after the second dose. Ninety-five per cent of the
participants had antibodies against the vaccine at week 18 and 72% had
antibodies at week 48.
How did the researchers
interpret the results?
The researchers say that
in this first phase I trial with the HIV/AIDS vaccine candidate MVA-B in healthy
volunteers the vaccine was safe and well-tolerated and elicited strong and
durable T-cell responses in 75% of volunteers. They say that their data support
further exploration of MVA-B as an HIV vaccine candidate.
Conclusion
This phase I trial showed
that this HIV vaccine was well-tolerated and did not lead to serious adverse
effects in a small group of healthy volunteers. The vaccine was also shown to
cause a T-cell immune response in 75% of the 24 participants and to cause
antibody responses in 95%.
These results are
encouraging and will probably mean that the researchers go on to look at safety
and immune response to this vaccine in a larger group of people. There are two
potential ways in which vaccines could be used to fight HIV. A vaccine may
either be used as a prophylactic to stop people being infected with the virus,
or therapeutically, to help the body to lower HIV levels once a person has
already been infected. The aim of therapeutic use would be to reduce disease
symptoms.
This study did not look at
the effectiveness of the vaccine, including how well it could protect against
infection with HIV or lower HIV levels in the body of people already infected.
Further research is needed
to test the vaccine in these two areas - preventing HIV infection or reducing
the number of virus particles in infected people. Also, other studies are
looking at potential HIV vaccines, and research will be needed to test how well
this vaccine compares to these.
September 27, 2011
Long-awaited results from
a Phase II study of ibalizumab, an antibody-based therapy that has been in early
stage development for several years, were reported at the 51st Interscience
Conference on Antimicrobial Agents and Chemotherapy (ICAAC) on September 17 in
Ibalizumab is an experimental entry inhibitor being developed by TaiMed
Biologics, a biotechnology company with research facilities in
Because of ibalizumab’s unique mechanism of action, researchers have long
believed that the drug holds tremendous promise as an HIV treatment,
particularly for people with multiple-drug-resistant strains of the virus.
Ibalizumab is currently administered intravenously in an outpatient setting. To
date, the drug has been given by researchers once weekly and every other week,
using a dose that depends on body weight.
With the successful completion of a variety of early stage studies, including a
48-week Phase IIa study reported in 2006 demonstrating statistically significant
viral load reductions compared with placebo, a Phase IIb study was started in
August 2008. Twenty-four week data from the latest study were reported at ICAAC
by Stanley Lewis, MD, PhD, of TaiMed.
Unlike the weight-based dosing used previously, the Phase IIb study explored two
fixed doses: 800 milligrams (mg) administered intravenously once every two weeks
and 2,000 mg given every four weeks. The clinical trial enrolled 113 people
living with HIV with resistance to multiple drugs, including at least one drug
in the three major classes of antiretrovirals (the nucleoside reverse
transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and
the protease inhibitors).
Both doses were combined with an optimized background regimen containing at
least one drug the patients’ viruses were sensitive to. Of note, no placebo
for comparison purposes was used in the study.
After 24 weeks, viral loads were reduced, on average, by 1.5 log in both
treatment groups. Undetectable viral loads were documented in 44 percent of
those in the 800 mg ibalizumab group and 28 percent in the 2,000 mg ibalizumab
group. CD4 counts increased by 63 cells and 80 cells, respectively.
Though these viral load reductions are notable, the lack of a placebo group in
the study prevents firm conclusions about ibalizumab’s potential. For example,
it remains unclear how much of the viral load reductions seen in both treatment
groups were attributed to the ARVs used in combination with ibalizumab.
Encouragingly, Lewis reported that ibalizumab was well tolerated with no
drug-related deaths, serious side effects or discontinuations. Though some
laboratory abnormalities were reported, these were not associated with any
“clinically meaningful” problems. The most common side effects were rash,
diarrhea, headache and nausea, which appeared to be more common in the 2,000 mg
dosing group.
Going forward, TaiMed plans to use the lower dose of the drug to minimize the
risk of side effects without compromising efficacy. The company is also
experimenting with a subcutaneous version of the drug—administered using a
hypodermic needle to deliver ibalizumab directly under the skin—to allow for
once-weekly injections at home.