Compiled by Robert Fieldhouse
Boys less likely to catch HIV from mum
Baby
boys have a lower risk of acquiring HIV from their mothers than girls, researchers
have found.
This is the case even after preventative methods such as elective Caesarean
sections and AZT are taken into account, they suggest. But it appears gender
difference in infection rates disappear when expectant mums are treated with
combination therapy. Italian researchers examined mother-to-child HIV transmission
rates in more than 4,000 infants between 1985 and 1995 and 1996 and 2001.
The overall transmission rate across both periods was 478 (12 per cent), but
the rate among boys was 10 per cent while it was 13 per cent for girls.
In the earlier period, HIV transmission rates were similar in boys (16 per
cent) and girls (18 per cent). But after 1996, only three per cent of boys
became infected compared with six per cent of girls.
Boys were less likely to acquire HIV from their mothers, irrespective of whether
they were born through a vaginal delivery or Caesarean section or when AZT
was used alone to prevent infection.
But there was no difference in transmission rates in mothers treated with
combination ARVs.
JAIDS 40: 479-485, 2005
Company to trial once-daily doses of new inhibitor
Gilead Sciences is poised to evaluate three different once-daily doses of
its up and coming integrase inhibitor GS9137.Integrase inhibitors are a new
class of antiretroviral drug
currently in development. If proven effective, they could be a lifeline for
highly treatment-experienced people with virus resistant to existing classes
of HIV drugs.
The company will use a larger phase II clinical trial in the first half of
this year to try 20mg, 50mg and 125mg doses, each boosted with 100mg of ritonavir.
Food supplement may repair nuke damage
A single-patient case study has suggested a role for a commonly used dietary
supplement in treating damage to muscles connected to bones. The case study
showed the mitochondrial antioxidant coenzyme Q10 could treat ‘ragged
red’ fibre myopathy associated with use of nukes (nucleoside analogues).
Usually this damage is reversible with discontinuation of the drug causing
the problem. A 52-year-old man living with HIV for 14 years developed skeletal
myopathy while on effective AZT treatment. He started treatment with Q10 and
made a remarkable recovery, avoiding the need to change his antiretroviral
medication. Larger controlled trials will be needed to confirm these findings.
International Journal of STD & AIDS 16 (12):
827-829
Diverse HIV strains circulating in UK
Evidence is emerging that HIV strains other than the common subtype B are
being transmitted in the UK.
The evidence was presented by researchers at a south London HIV clinic with
an ethnically diverse patient population.The majority of white HIV positive
gay men carry the subtype B virus, common in Western Europe and North America.
For many years the viral diversity of HIV in the
UK has begun to more accurately reflect the global picture of HIV, with an
increase in the proportion of non-B strains.This is mainly in people who have
acquired their infection abroad. Until now there was no evidence non-B strains
were being transmitted within the UK.
King’s College Hospital sequenced blood samples from 344 people to identify
their HIV strain. In total, 223 carried a non-B subtype. Only 17 of the African
patients were thought to have acquired their HIV infection in the UK.Twenty-one
caucasian people were shown to have been infected with a non-B strain; 15
most likely in the UK.Researchers found that all 13 of the African- Caribbean
patients were thought to have acquired their HIV in the UK. With increased
international travel and migration, the diversity of HIV in the UK may continue
to increase, alongside those ‘global’ strains now within the UK.
JAIDS 41: 201-209, 2006
Four-drug hope for treatment experienced
Treatment-experienced people with low, detectable viral loads could benefit
from switching to
tenofovir plus Trizivir (AZT/3TC/abacavir), a new study suggests.
German doctors analysed the treatment response of 116 treatment-experienced
people who switched
to the twice daily co-formulation Trizivir plus once-daily tenofovir.
The majority of patients were in their early 40s and had previously used seven
different antiretroviral drugs over six and a half years. The average viral
load of participants was 371 copies and the average CD4 was 289. Twenty-four
weeks after switching, 85 per cent were still taking the four-drug regimen.
CD4 counts increased to an average of 345 cells and viral load declined to
an average of 69 copies.
The study authors concluded: “The simple combination therapy of tenofovir
plus Trizivir may be a viable, longer-term option in highly-experienced patients
with lower viral loads.”
H520*
Liver protein link to HIV progression
Raised
levels of a liver protein have been linked to increased rates of
illness progression among gay and bisexual men. C-reactive protein (CRP) is
a protein only produced by the liver during episodes of acute inflammation.
Researchers from the Multicenter Aids Cohort Study (MACS) in the US say men
with a CRP level greater than 2.3mg/L are at an increased risk of progression
from HIV to Aids. They also found that CRP levels increased significantly
over time, even in people who did not progress to Aids, but those who did,
experienced the greatest increases in CRP over time.
The MACS study looked at blood samples of over 1,600 gay and bisexual men
stored before the introduction of HAART and matched the results over time
with how the men actually progressed.
Previously the study shared an association between higher viral load and lower
CD4 count.
In the general population, higher CRP levels are associated with heart disease.
MACS researchers suggest the higher rates of CRP among a subgroup of HIV positive
gay men could have potential implications for their future risk of heart disease.
Arch Intern Med 2006; 166:64-70
T-20 can prevent mother-to-child transmission
While newborn baby boys may have a lower risk of acquiring HIV from mums,
new research suggests a role for the fusion inhibitor T-20 (Fuzeon) in the
prevention of HIV transmission in all births.
Doctors from St George’s Hospital, London, have reported two cases of
HIV transmission being prevented from women with multidrug resistant HIV to
their babies when T-20 was included in the women’s HIV combination.
T-20 did not cause any side effects in the newborns as it did not cross the
placenta.
The first case involved a heavily pre-treated 36-year-old whose viral load
at the sixteenth week of pregnancy was 20,000 copies and whose CD4 count was
98. HIV drug resistance testing showed multiple major resistance mutations
and she started a combination of abacavir, delavirdine, fosamprenavir and
atazanavir.
Initially her viral load fell to undetectable. However, by week 32 of pregnancy
it had climbed again to 1,362 copies. At this point T-20 was added to her
regimen and she gave birth
in week 39 of pregnancy by Caesarean section. At the time of delivery, her
viral load was undetectable and her CD4 almost 200. The baby received treatment
with 3TC and lopinavir/ritonavir. Four separate HIV tests over four months
confirmed the baby to be HIV negative.
The second case concerned a heavily pre-treated 33-year-old whose CD4 count
at the sixth week of pregnancy was 75 cells and whose viral load was 20,000
copies. She too had multiple resistance mutations.
Therapy with nevirapine, tenofovir, fosamprenavir and ritonavir was initiated.
However, by week 32 her CD4 cell count had fallen to 51 cells and her viral
load had risen to 31,000 copies. At this point T-20 was added to her combination.
After two weeks her viral load had declined to 305 copies and her CD4 count
risen to 135 cells and she had a Caesarean section. The baby was again treated
with 3TC and lopinavir/ritonavir and remained HIV negative.
T-20 penetrates the genital tract poorly and women taking it to prevent mother-to-child
HIV transmission are likely to need a Caesarean section, rather than opt for
a vaginal delivery.
AIDS 20: 297 - 299, 2006
DHEA helps beat depression
New research suggests the UK-banned supplement DHEA is an effective treatment
for low-level depression in people with HIV. This is of particular interest
to people living with HIV as declining levels of DHEA have previously been
associated with faster progression to Aids.
In this eight-week trial, 145 HIV positive people with depression received
either DHEA, dosed flexibly from 100 to 400mg each day, or a placebo. Depression
improved in 62 per cent of the people taking DHEA, compared to just 33 per
cent on the placebo.
There were few side effects and no significant changes in CD4 cell count or
viral load in either treatment group. Further long-term data in a broader
patient population is needed. Over-the-counter sales of DHEA are banned in
the UK but it is available via internet pharmacies.
American Journal of Psychiatry, 2006; 163: 59-66
Woman catches HIV from her doctor during
childbirth
A
Spanish woman has become HIV positive from her obstetrician during a Caesarean
section.
The doctor was unaware of his HIV status at the time of the procedure and
the infection appears to have been caused by a needle stick injury. Anaylsis
of the obstetrician’s and the woman’s HIV strain makes it highly
likely the doctor is the source of the infection. The 32-year-old had a negative
HIV test during pregnancy. Two weeks after the Caesarean section, she developed
a high temperature, swollen glands and rash. A test eight weeks later showed
her to be HIV positive. Her CD4 count was 607 and her viral load 1,400. Her
baby and partner both tested HIV negative. The doctor admitted to having had
a needle stick injury during the procedure. Seven months after the Caesarean,
the doctor took an HIV test and it was positive. His CD4 count was 720 and
his viral load 1,500 copies. AIDS 20: 285 – 287, 2006.
TB drug weakens HIV protease inhibitor
A commonly used drug to fight TB significantly decreases concentrations of
the protease inhibitor atazanavir in the blood, a study has found.Researchers
in Spain designed a trial to test whether boosting atazanvir with ritonovir
might overcome its interaction with rifampin. It is common in the UK to boost
atazanavir with a small dose of ritonavir. People taking a triple nucleoside
analogue regimen plus anti-TB therapy added ritonavir-boosted atazanavir.
But the study was stopped within three weeks as researchers found that three
patients had blood levels of atazanavir far below the recommended therapeutic
level, despite them taking ritonavir.
A1202*
Once-daily lopinavir helps people stick to
meds
A new, once-daily tablet version of the protease inhibitor lopinavir (Kaletra)
has been licensed in the US and is due to be licensed in Europe later this
year.Lopinavir is currently taken as three capsules, twice-daily.
Researchers have demonstrated that once-daily lopinavir is as effective as
twice-daily and it improves adherence. Nearly two years into therapy, people
on once-daily lopinavir took nine out of ten doses appropriately compared
to only eight out of ten on the twice-daily pill.
In a separate study, 15 HIV negative people switched from taking the current
formulation of lopinavir to the new tablet formulation once-daily. It concluded
that concentrations of lopinavir and ritonavir were generally higher with
the new tablet formulation. Importantly, the tablet formulation demonstrated
a lower rate of side effects, particularly diarrhoea. Further studies of once-daily
lopinavir/ritonavir in this new tablet formulation in both treatment-naive
and treatment-experienced studies are either currently underway or planned.
The new tablet version of lopinavir should be licensed in Europe later this
year. The once-daily licence will follow. H522*, H1894*
Royal Free gets new liver damage test
The HIV/HCV clinic at London’s Royal Free Hospital has become
the first in the UK to introduce a new, non-invasive test, which holds promise
as a tool to diagnose liver damage (fibrosis) in people coinfected with HIV
and hepatitis.
This new technology, the Fibro Scan, may reduce the need for the often painful
procedure of liver biopsies in co-infected patients. Doctors at the Royal
Free will be researching its usefulness in detecting fibrosis in co-infected
people in order to replace biopsy in the management of their hepatitis.
Research has previously showed the FibroScan to be effective in HIV-negative
people and French researchers have recently reported encouraging research
in co-infected patients.
The new five-minute, painless procedure measures the stiffness of the liver,
which the French research suggests matches the degree of liver fibrosis detected
by biopsy.
JAIDS 41: 175-179, 2006
Scotland turns down tipranavir
The
Scottish Medicines Consortium (SMC) has refused to make the recently licensed
protease inhibitor (PI) tipranavir (Aptivus) available.
The drug could have benefited treatment-experienced people whose HIV had become
resistant to other PIs.
The new PI is available in the rest of the UK. SMC advice stated: “Tipranavir
is more expensive than other protease inhibitors and the economic case for
its use has not been demonstrated.”
However, doctors in Scotland will be able to override the decision if they
feel a patient warrants the treatment. While the drug is more expensive at
£490 a month, a large 48-week trial demonstrated it to be the most effective
therapy for people who had experienced failure with other PIs.
The SMC refused to comment on the decision but Brian West, of charity HIV
Scotland, told PN it was doing all they could to make sure the decision did
not affect patient care.
“While doctors in the larger Scottish centres may feel confident to
ignore the advice from the SMC,” said West, “it is possible that
others may be denied access to the drug, potentially prompting people to travel
south of the border for treatment.”
Four-drug therapy proves no better
People who start therapy with very advanced HIV fare no better in the short-term
if they begin with
two nukes (nucleoside analogues) and two PIs (protease inhibitors), compared
with those who take a
single PI and two nukes.
Advanced HIV illness is defined as a CD4 count under 200 cells and a viral
load greater than 100,000. The 30-person study failed to show that viral load
fell more quickly and CD4 cells rose higher if saquinavir and nelfinavir were
taken together. International Journal of STD & Aids 16 (12):807-810
New PI moves forward
An experimental protease inhibitor (PI) currently in clinical development
may be effective in people with PI resistant-virus. Brecanavir (GW640385)
has demonstrated activity against multiple protease inhibitor-resistant HIV
in the test tube, appearing up to 100 times more potent than older PIs.
Thirty-one HIV positive adults received 300mg of brecanavir twice-daily boosted
with 100mg of ritonavir plus two nukes (nucleoside analogues). Eighty-one
per cent achieved a viral load below 400 copies at week 24 and 77 percent
went below 50 copies. The average increase in CD4 cell counts over this period
was 84 cells.
Patients with PI-sensitive and highly PI-resistant virus responded in a similar
way.
Participants reported side effects as being mild, requiring no treatment modification
or discontinuation. Brecanavir is expected to enter the next stage of development
later this year.
H412*
Yoghurt bacteria may fight HIV
Scientists claim to have genetically modified some of the ‘friendly
bacteria’ found in yoghurt to release a drug that blocks HIV infection.
The bacterium Lactococcus lactis was genetically modified to generate cyanovirin,
a drug which has prevented HIV infection in monkeys and human cells. It will
move forward into human trials next year. Cyanovirin is a small protein taken
from a bacterium normally found in water. It latches onto the outer coat of
HIV, preventing the infection of cells, and is also currently under investigation
as a microbicide.
