Compiled by Robert Fieldhouse
HIV treatment breaks ‘OK for some’
Early results from a small study of 74 people living with HIV suggest CD4-guided
treatment breaks may be safest for people with high CD4 counts. Structured
treatment interruptions of this kind re-initiates combination therapy before
the CD4 count falls below a specific level.However, researchers have cautioned
that doctors should not use treatment interruptions routinely until they have
been tested in larger groups of people living with HIV. People who had previously
used therapy containing two nucleoside analogues were randomised to three
groups. One received the ritonavir-boosted protease inhibitor saquinavir with
two nucleoside analogues continuously, another took a CD4-guided treatment
interruption, while the third took treatment on a week-on-week-off cycle.The
week-on-week-off arm was stopped early as almost half the patients on this
strategy
experienced virologic failure. Nineteen of 23 patients in the treatment interruption
arm restarted HAART after periods ranging from 12 to 96 weeks.More than 70
per cent in this group saw their CD4 counts remain above 350 cells during
the 96-week randomised phase.In the final 12 weeks, when all patients received
triple combination therapy, the proportion of patients with viral load below
400 copies increased from 30 to 91 per cent. Rates of clinical disease progression
did not differ between the groups at the end of the 12 week treatment phase
and rates of adverse events were similar for continuous and CD4-guided treatment.
SMART, the largest structured treatment interruption trial, is currently enrolling
a large number of patients to find out if this strategy is clinically safe.
Journal of Acquired Immune Deficiency Syndromes (JAIDS), 2005; 39: 523-529.
Is HIV weakening?
A new small study suggests HIV may be weakening after more than 20 years of
mutations and several million deaths.Samples of HIV-1, taken from patients
in the 1980s and again in 2002-3, were compared by researchers at Antwerp’s
Institute of Tropical Medicine. The researchers found the newer samples did
not multiply as well and were more sensitive to drugs. One of the researchers,
Dr Eric Artz, said: “Obviously, the virus is still causing death, although
it may be causing death at a slower rate of progression now. Maybe in another
50 or 60 years we might see this virus not causing death.”It had once
been argued that the virus would become increasingly virulent as it passed
through more and more human hosts; in fact, the opposite appears to be true.
The virus passed on now may well be less ‘fit’ each time it is
transmitted. However, the study is very small; evaluating only 12 samples
at each point and alterations in HIV’s ability to reproduce itself is
most likely best identified over generations, not a period of 15 or so years.
Because all the blood samples of HIV came from people who had never used treatment,
the lack of ‘fitness’ cannot be attributed to the use of antiretroviral
drugs. The researchers stressed that their findings should not be taken as
a green light to scale down HIV prevention initiatives around the world. Bruce
Wainwright AIDS 19; 1555-1564, 2005
Pussy; purrfect possibilities for prevention?
New research showing cats vaccinated with an experimental form of HIV are
as well protected against the feline version of HIV (FIV) as those receiving
the FIV vaccine may have implications for human vaccine development. Some
compounds made from separate virus strains have been successfully used in
vaccines against viruses from the same subfamily, such as smallpox in humans,
which is made from cowpox.
AIDS 19 (14):1457-1466, 2005
Homeopathy acts as ‘placebo effect’
People
who experience clinical benefit from homeopathic medicine are just experiencing
placebo effects, according to scientists.Researchers from Switzerland and
the Medical Research Council reviewed the quality of trials evaluating the
effects of homeopathic and allopathic medicine and found weak evidence for
a specific effect of homeopathy.They compared results from 110 homeopathy
trials with results from 110 conventional medicine trials. The researchers
said: “When analyses were restricted to large trials of higher quality
there was no convincing evidence that homeopathy was superior to placebo,
whereas for conventional medicine an important effect remained.”Lancet
editors said: "Now doctors need to be bold and honest with their patients
about homeopathy's lack of benefit, and with themselves about the failings
of modern medicine to address patients' needs for personalised care."Lancet
2005; 366:690-692,726-732.
Fewer people stopping HIV therapy
Researchers have compared treatment discontinuation rates among Europeans
with HIV who began therapy before and after 1999.The study of 1,198 people
found that a year after beginning treatment, six per cent of those who started
post-1999 had stopped all antiretrovirals while one in four had changed at
least one drug.
Overall, 70 per cent stayed on their original regimen. Drug side effects were
the main reason for stopping or switching drugs, in just under one third of
patients.People starting therapy after 1999 were significantly less
likely to stop or switch therapy than those who started before. They had a
72 per cent lower rate of stopping or switching drugs due to side effects.This
suggests encouragingly that treatments are becoming more tolerable with time.People
coinfected with hepatitis C (HCV) stopped or switched antiretrovirals 46 per
cent more than others and were more likely to stop some or all their drugs
because of side effects or patient/doctor choice.The European team that conducted
the study said: “Managing side effects must remain a key intervention
in maintaining HAART.” They added that further studies were needed to
look at the
“relationship between HCV, specific antiretrovirals, and different treatment
strategies.”
Aids Research and Human Retroviruses 2005; 6: 527-536.
Treatment reduces HIV in amniotic fluid
A
study of HIV positive pregnant women treated with nevirapine or AZT failed
to detect virus in their amniotic fluid and foetal cord blood samples.South
African researchers studied 26 pregnant women with full-term, uncomplicated
pregnancies who gave birth to babies by Caesarean section. Their CD4 counts
ranged from 158 to 654 cells and their viral loads from below 400 copies to
169,990 copies.The women took either single-dose nevirapine at least four
hours before having the Caesarean section or 300mg AZT twice-daily from 34
weeks of pregnancy and at least three hours before the operation. Cytomegalovirus
was detected in four fluid samples. None of the babies were born HIV positive.The
authors concluded: “Although the exact mode of HIV transmission in-utero
remains speculative, our data suggest that, in normal, uncomplicated pregnancies,
before the onset of labour or rupture of the amniotic membranes, the amniotic
fluid is free of HIV.
“Thus, the foetus is not exposed to HIV-infected amniotic fluid before
the onset of labour and/or rupture
of the amniotic membranes.” Journal of Infectious Diseases 2005; 192:
488-491
medical notes
Fat loss most likely symptom of lipodystrophyLosing fat on
the arms, legs and stomach are the most common ways men with HIV are affected
by body fat changes. A US study compared fat loss in 425 men
living with HIV against a group of negative men. Treatment with d4T or indinavir
raised the risk of losing leg fat, while use of nevirapine was linked to reduced
fat on the stomach. JAIDS 2005:121-131.
Lipodystrophy stable in children during two years
A French study of 66 girls and 64 boys taking HAART found changes, such as
increased cholesterol and body fat changes, remained stable over two years
of treatment.However, insulin resistance doubled over two years, affecting
13 per cent of the children. Around a quarter of the kids, whose average age
was ten, had lipodystrophy, while just over one in five had elevated cholesterol
levels.JAIDS 2005; 40:161-168
HIV drug shows promise
Large clinical trials in 2006 will test a pioneering drug called a maturation
inhibitor. Panacos Pharmaceuticals believe that PA-457 could be effective
against HIV strains resistant to current drugs. In recent studies the drug
demonstrated an average 90 per cent decrease in virus at the highest dose
(200mg once daily). Reported side effects were mild or moderate. PA-457 works
by disrupting a late step in HIV’s replication cycle by warping the
shape of the newly developed HIV core protein, capsid. This blocks replication
of infectious HIV. www.panacos.com
Jaundice linked to genetics
Research suggests people with a particular genetic profile are most likely
to experience high bilirubin levels with the protease inhibitors (PIs) atazanavir
and indinavir.Researchers analysed the UGT1A1*28 gene in 96 HIV positive people
whose bilirubin levels were measured over an average of six years. Bilirubin
is one measure of how well your liver is functioning and high levels lead
to jaundice.Treatment with atazanavir raised bilirubins 15 µmol/L above
the average and indinavir boosted levels to eight µmol/L.People carrying
two copies of the gene had bilirubin levels an average 5.2 µmol/L above
the group level. Taking efavirenz lowered bilirubin levels.Researchers suggested
that looking for this gene before starting therapy would identify HIV positive
individuals at risk for hyperbilirubinemia and decrease episodes of jaundice.
Journal of Infectious Diseases 2005; 192: 1381-1386.
New non-nuke development
An investigational non-nucleoside reverse transcriptase inhibitor (NNRTI),
GW695634, significantly reduces viral load in people resistant to nevirapine,
efavirenz or delavirdine. Forty-six people with an average of two key NNRTI
resistance mutations received one of four doses (100, 200, 300 or 400mg) twice-daily
or a placebo. Fifty-five per cent had the K103N mutation which signifies resistance
to all currently available NNRTIs. After one week, people achieved an average
viral load decline of between 1.1 and 1.6 log. This is greater than a ten-fold
change and is considered a significant reduction in virus levels.
WePeb.2C03, 2005. 3rd IAS Conference, Rio de Janeiro
