Robert Fieldhouse reports from the Third International Aids
Society Conference, Rio de Janeiro
Strong results for tenofovir/3TC/efavirenz
A once-daily combination of tenofovir, 3TC and efavirenz has proved to be
well-tolerated and potent in the medium term. A clinical trial of 86 people
taking this combination over four years found 87 per cent
maintained a viral load below 50 copies. The average CD4 rise over this period
was 391 cells.
No patient stopped tenofovir therapy due to kidney problems. Hip and spine
bone mineral density decreased slightly in the first 48 weeks of treatment,
but no further declines were noticed during years two, three or four. WePe6.3C05
Remune may lengthen treatment interruptions
People with HIV who received an investigational therapeutic vaccination while
on a so-called
treatment ‘holiday’, faired better than those who did not. People
given the vaccine Remune during a treatment interruption saw less significant
increases in viral load and less significant declines in CD4 count.
Therapeutic vaccinations are intended to stimulate the immune system to recognize
HIV, boosting the immune system’s response to HIV by increasing the
range of CD4 and CD8 cells with specific activity against HIV. Best responses
were achieved in people who had previously taken Remune while on antiretroviral
therapy in an earlier study. Further studies are planned to determine how
a therapeutic vaccination such as Remune may be best used in HIV care.
WePp0402*
Atazanavir safe during pregnancy
New
research suggests the protease inhibitor atazanavir is a safe treatment for
women
who are pregnant or who are considering having children. Researchers looked
back at the records of nine HIV positive women who took atazanavir up until
February 2005. By the time of delivery all of the women had viral loads below
100 copies and CD4 counts had risen from an average of 366 to 450. All children
were born HIV negative and only three had mildly elevated bilirubin levels,
with two of the babies requiring brief phototherapy. No liver, kidney or pancreas-related
side effects were reported. TuPe5.2P01*
Saquinavir failure does not rule out other
PIs
People
experiencing treatment failure on ritonavir-boosted saquinavir as first-line
therapy can still benefit from treatment with other protease inhibitors (PIs)
in the future, a new study suggests.
Those who achieved an undetectable viral load on saquinavir who then became
‘detectable’ again, did not appear to develop major PI resistance
mutations that make future treatment with other PIs less effective.
Saquinavir plus two nucleoside analogues were given to 258 people on first-line
therapy for six months. It proved a potent combination with 91 per cent of
participants getting a viral load below 50 copies at 24 weeks. Viral load
became detectable in just four per cent of participants after an average of
30 weeks.
However, no significant resistance mutations to either saquinavir or any of
the other currently available protease inhibitors were identified by resistance
testing. A similar finding has previously been reported with the ritonavir-boosted
protease inhibitors lopinavir and fosamprenavir. Ritonavir-boosted saquinavir
is now available re-formulated as Invirase, with two tablets taken twice-daily.
WePe4.4C12*
Crystal may fuel transmission of resistant
HIV
HIV
positive people using crystal meth are more likely to disregard safer sex
practices, a new US
survey suggests.The US study found that crystal methamphetamine use by HIV
positive people quadrupled the risk of having unprotected anal or vaginal
sex with an HIV negative partner or a with a person whose HIV status was unknown.
In addition, using the anti-impotence drug Viagra increased the likelihood
of having unsafe sex with a partner whose HIV status was not known in the
preceding four months. Researchers interviewed 168 men and 21 women with detectable
viral loads and known drug resistance while receiving antiretroviral treatment.
At one or more clinic visits, more than a quarter of those interviewed reported
having had unsafe sex with an HIV negative partner or a person of unknown
HIV status. Over one third had resistance to a drug from each of the three
commonly prescribed classes (nukes, protease inhibitors (PIs) and NNRTIs),
while one quarter had resistance to NNRTIs and PIs.
A separate report in the August issue of the American Journal of Psychiatry
linked crystal meth use by people living with HIV with alterations in the
size their brain which may lead to cognitive impairment such as difficulties
learning or processing information. Researchers compared brain scans of HIV
positive or negative crystal users with those of HIV positive and negative
people who had never used crystal and concluded that concurrent crystal use
and being HIV positive might cause greater cognitive impairment than each
condition on its own. While HIV infection was linked to loss of volume in
the cerebral cortex, which is associated with worsening cognitive function,
the crystal users were also shown to have increase in a part of the brain
know to affect motor function and motivation. UKC is currently conducting
research into crystal meth use by gay men in London. For further details,
contact Jack Summerside on 020 7564 2180. MoPpLB0105*
Crock of shite or croc’ of gold?
Australian researchers are busy testing the blood of crocodiles after tests
revealed their immune systems are able to kill HIV. They hope to be able to
isolate powerful antibodies which could be used to develop new treatments
for HIV and other infections.
Benefit of 3TC over full therapy interruption
HIV
positive people who continue to take only the nucleoside analogue 3TC during
a treatment ‘holiday’ develop fewer symptoms. A study found continued
use of 3TC during the break also led to less significant CD4 declines and
less substantial rises in viral loads. These conclusions were based on the
final 48 week results from a study of 50 HIV positive people who wanted to
stop treatment after their viral loads became detectable again. Maintaining
3TC therapy alone seems to make it more difficult for HIV to reproduce itself.
This is also the case for people who have developed resistance to the drug.
Taking 3TC alone may be a useful strategy for people with high levels
of drug resistance who are waiting for two or three new potent antiretrovirals
to become available in order to construct a new treatment line.
WeFo0204*
in the pipeline
Is valproic acid an HIV cure?
In a preliminary study, valproic acid was used to awaken dormant HIV, providing
hope for its eventual eradication from the body. Valproic acid is already
licensed for the treatment of bipolar disorder and epilepsy, and US researchers
tested the effects of it in four people living with HIV for three months.
They found the pool of dormant HIV infected cells was reduced by 75 per cent
in three.
It’s thought the drug reactivates the virus in dormant cells and either
wakes it or kills it. If every dormant cell in the body were targeted and
purged it may be possible to take treatment for only two or three years before
the virus is eradicated. Other researchers questioned the research saying
that when the valproic acid is stopped the virus rapidly returns, even if
you only have one dormant virus-infected
cell left. Lancet 366: 549-555, 2005
GSK halt study
GlaxoSmithKline has halted its study of the experimental CCR5 inhibitor aplaviroc
in people starting therapy, after reports of severe liver side effects.Studies
in treatment-experienced patients will continue, but participants will be
closely monitored for signs of liver toxicity. It is still unknown if the
CCR5 inhibitor may drive a switch to the more harmful X4 virus in people with
advanced HIV disease. If you are taking a CCR5 inhibitor in one of the treatment
experienced trials, you should speak to one of the trial investigators.
Reverset
Reverset is a nucleoside analogue similar to 3TC and not a non-nucleoside
reverse
transcriptase inhibitor as PN reported last month. It should not be taken
with ddl and may be useful for people with resistance to 3TC and FTC.
Compound effective against multi drug-resistant HIV
Australian biotech firm Biotron says its Virion compound works against drug-resistant
HIV. This treatment works at a later stage than all major HIV drugs currently
available. It prevents infectious viruses from leaving cells and works in
monocyte/macrophage cells, where there is often a reservoir of virus unaffected
by current antiretroviral treatments. Virion is currently undergoing final
safety studies and so-called ‘proof of concept’ trials required
for regulatory approval are expected by the end of this year. The biotech
plans to partner with a major pharmaceutical company within the next 12 months.
www.biotron.com.au
New protease inhibitor proves its potency
The new investigational protease inhibitor, TMC-114, appears potent when dosed
twice daily with ritonavir, even if you have used PIs in the past and have
multiple PI resistance mutations.
Researchers recruited 318 HIV positive people to test one of four doses of
TMC-114, developed by Janssen-Cilag, or a currently licensed protease inhibitor.
Sixty-five received 600mg of TMC-114 with 100mg of ritonavir twice-daily.
Over half of these recorded a viral load below 50 after 24 weeks of treatment.
If the fusion inhibitor T-20 was included in the combination, the proportion
of people whose viral load went below 50 copies at 24 weeks increased to 63
per cent.These are impressive results considering the amount of treatment
experience the trial participants will have had.
WeOaLB0102*
