Compiled by Robert Fieldhouse
Three common nukes found to increase diabetes
risk
A
major study into the long-term side effects of antiretroviral drugs has found
three ‘nukes’ are associated with development of new onset diabetes.
The drugs were the nucleoside analogues (NRTIs) d4T (Zerit), ddI (Videx) and
AZT (Retrovir), also used in Combivir and Trizivir.
The non-nuke nevirapine (Viramune) appeared to have a protective effect and
no protease inhibitor was shown to be linked with development of diabetes.
The DAD study (Data Collection on Adverse Effects of Antiretroviral Drugs)
involves 33,389 people living with HIV across three continents.
Now in its sixth year, DAD is beginning to be able to distinguish between
the side effects of individual drugs and drug classes.
One in 35 DAD patients had diabetes on entering the study. During the six
years of follow-up, a further 745 patients were diagnosed with diabetes.
Investigators calculated a six per cent rise in risk of diabetes for every
year on antiretroviral therapy, although the increase appeared to level off
somewhat after four years of treatment.
Nevirapine appeared to have a protective effect, as the risk of new onset
diabetes reduced by 11 per cent for every year on the drug.
d4T was most significantly associated with new onset diabetes, the risk increasing
by 19 per cent for every year spent on the drug with no apparent leveling
off over time.
DdI and AZT were also associated with increased risk of diabetes though they
carried the same relative risk as antiretroviral therapy in general at six
per cent a year.
Diabetes risk was significantly associated with rises in cholesterol, triglycerides
and the development of body fat wasting and with falls in ‘good’
HDL-cholesterol.
Being obese, male, black and older was also associated with diabetes while
smoking was not.
Researchers said it remains unknown whether d4T directly impaires glucose
tolerance or whether diabetes develops as a consequence of body fat loss.
• Abstract PL9.5. 8th International Congress on Drug Therapy in HIV
Infection, Glasgow, 2006.
Super-vaccines on the way
More effective and easier-to-administer vaccines could soon protect millions
of people from malaria, TB and HIV, thanks to a breakthrough from a global
research team.
Scientists have been genetically modifing virus DNA to produce disease-killing
antigens, instead of just reproducing itself.
Vaccines cause our bodies to produce antibodies to fight off infection in
the blood. But antibodies can’t get inside cells where many diseases
hide.
Not only can this new type of vaccine get inside the cell, but it also produces
chemicals that stimulate the body's immune system producing a stronger and
longer lasting response.
Vaccines also need to be frozen during transportation and storage and nearly
half are wasted because of this.
With this in mind, the same team, led by Professor Adrian Hill from University
of Oxford, approached a biosciences company that has come up with a new vaccine
formulation.
By removing the water from the vaccine and turning it into a powder, it no
longer requires storing at -80°C. It can be made injectable again on site.
Fat blocker helps HIV-related metabolic problems
A potent fat-regulating drug can improve triglyceride levels and insulin
sensitivity in people living with HIV with metabolic disturbance, according
to new research.
Acipimox helps prevent lipolysis; the breakdown of fat stored in fat cells
that can lead to raised lipids in the blood (dyslipidemia) and lipodystrophy.
Researchers evaluated the safety and efficacy of acipimox in 23 HIV positive
men and women with elevated triglyceride levels and abnormal fat distribution.
None were on lipid-lowering therapy.
For three months, 11 people took 250mg of acipimox three times daily and 12
people took placebo.
Those taking Acipimox showed significantly reduced levels of lipolysis and
a 68 per cent reduction in circulating free fatty acids.
This was accompanied by a significant but modest triglyceride reduction and
significant improvements in insulin sensitivity. These metabolic improvements
were not seen with placebo.
The researchers concluded that acipimox warranted further investigation as
a potentially useful agent for improving metabolic disorders in people living
with HIV.
• J Clin Endocrinol Metab 2006; 91:4438-4444
Immunotherapy may help suppress virus during
treatment interruptions
An experimental HIV vaccine appears to help people maintain lower viral loads
during treatment interruptions, according to latest research.
Researchers at the University of Alabama gave people with HIV on treatment
breaks the vaccine ALVAC. The vaccine uses canarypox virus that is harmless
to humans to carry certain HIV genes, but not the whole virus, into the body.
Researchers wanted to see if the vaccine would improve the way patients’
immune systems controlled HIV 12 weeks after stopping treatment.
A significantly greater proportion of vaccine recipients, 31 per cent, maintained
HIV viral loads below 5,000 copies beyond 12 weeks compared with just nine
per cent of those receiving placebo.
Adding the immune system stimulator interleukin (IL-2) failed to influence
the rate of HIV viral load rebound.
But people who received IL-2 experienced significantly greater CD4 cell count
increases compared with those who did not.
Three quarters of those given ALVAC plus IL-2 experienced serious side effects
compared with around a third of those given placebo plus IL-2.
After the participants restarted antiretroviral therapy their HIV was quickly
re-suppressed.
Further studies with more potent immunogens used during antiretroviral therapy
interruptions are needed to assess their potential role as therapeutic immunisations.
• J Infect Dis 2006;194:1672-1676
US poised to expand experimental meds access
US drug firms may soon make more experimental drugs available for a
fee to more patients with life-threatening illnesses with no approved treatments.
Plans for relaxing access to experimental meds have been proposed by the US
Food and Drug Administration (FDA). Drug companies would be allowed to charge
patients enough to cover costs directly linked to drug development as well
as administrative costs to make the products available, the FDA said
Experimental drugs not yet approved by the agency, have been available to
some patients on named patient programmes since the 1970s.
In the past, the FDA has permitted thousands of people with HIV, cancer and
heart problems to use drugs before they were approved. But agency officials
said current regulations caused confusion by not clearly stating when companies
could charge a fee. The new rules spell out access for individuals as well
as small groups of patients, the FDA said.
Women with HIV have fewer vaginal infections
on HAART
According
to new research, there has been a decrease in rates of certain vaginal infections
in women living with HIV. The US National Institutes of Health spotted the
improvement by evaluating 2,056 HIV positive and 554 ‘high risk’
HIV negative women annually between 1994 and 2003.
At the start, 42.8 per cent of the HIV positive women had bacterial vaginosis.
Vaginosis is on overgrowth of some of the normal vaginal bacteria. This compared
with 47 per cent of the HIV negative women.
The rates of infection with trichomoniasis, a single cell parasite, were 6.1
per cent in the women living with HIV and 7.8 per cent in those who weren’t.
The study also looked at yeast vaginitis, which had rates of 10 per cent and
3.8 per cent respectively.
Rates of bacterial vaginosis and trichomoniasis were seen to decrease significantly
in both groups over the nine years. However, rates of yeast vaginitis fell
only among women living with HIV.
Use of HAART was associated with the decreases in all three infections.
Researchers concluded: “Decreased rates of vaginal infections may decrease
the risk of transmission of HIV to sexual partners and newborns.”
• JAIDS 2006;43:161-168.
Hormone linked to HIV depression
Depression
in people with HIV-related dementia may be associated with a decline in a
key hormone, according to latest research.
The hormone somatostatin is produced mainly by a part of the brain, the hypothalamus,
that inhibits the secretion of various other hormones such as insulin.
In the past, reduced somatostatin has been associated with depressed mood,
and studies show HIV in the brain results in loss of brain cells that produce
the hormone.
Researchers carried out postmortem studies of 21 people with HIV within 24
hours of death.
Eight had HIV encephalopathy (HIV-related dementia) and five had no sign of
HIV brain disease; 14 had no documented history of major depression, while
seven had recorded major depression.
Somatostatin levels in the group with documented depression were 68 per cent
lower than those without history of major depressive disorder. Investigators
said the hormone “may play a primary role in the evolution of major
depressive disorder in the setting of HIV”.
• Neurology 2006;67:1867-1869.
Balls to viral replication
French scientists have shown that HIV reproduces in immune cells in
the testicles.
This explains the persistence of HIV virus in semen despite use of HAART.
Researchers at the National Institute of Health and Medical Research in Rennes,
France, examined testicle tissue for the presence of HIV receptors. They found
all the necessary cellular receptors (CD4, CXCR4, CCR5, and DC-SIGN) were
present on cells located within the testicles.
They grew human testis tissue in culture that was able to be infected by HIV.
The infected cells also produced new, active HIV.
The scientists said their finding that HIV can replicate within the testicles
is significant since many HAART drugs have difficulty penetrating this reservoir
and may be present at sub-therapeutic levels. Viral replication in the testes
may permit the continued spread of the virus in people with undetectable blood
viral loads.
• The American Journal of Pathology.
Selenium link to viral suppression
Taking
selenium, an antioxidant mineral, may modestly reduce the amount of virus
in your blood and raise your CD4 count, in addition to the effect you get
from HIV therapy.
Research has linked selenium deficiency to forms of heart disease and a weakened
immune system. Previous studies also have found that the mineral suppresses
HIV replication in the test tube and some people living with HIV have lower
selenium levels.
The study recruited 262 adults living with HIV between 2001 and 2005. Two
thirds were taking antiretroviral therapy when they started the trial.
One hundred and forty people to received 200µg of selenium daily in
the form of selenium yeast capsules, Selenomax, and 121 got placebo. After
nine months 174 participants remained in the study, 91 on selenium and 83
on placebo.
Results in the 50 people who responded with the greatest increases in blood
selenium levels showed that HIV viral load declined 12 per cent (by an average
of 10,000 copies over 9 months) and CD4 counts rose by an average of 30 cells.
The same effect was seen among people not on HIV therapy who were given selenium.
Around half of the people on HAART had detectable HIV viral load at the start
of the study. Of these, people who received placebo had an increase in viral
load twice as high as those receiving the selenium. This lead researchers
to conclude that selenium’s effect on viral load was independent of
the effects of antiretroviral therapy.
Additional research is needed to examine the mechanism behind selenium’s
effect on viral load, and to find out if the effect of supplementation on
the CD4 cell count results from viral load suppression, or whether selenium
also has additional immune benefits, is needed.
• Arch Int Med 167: 148-154, 2007.
HIV status irrelevant to decisions about
surgery
HIV
status should not be used to decide if a person should undergo surgery, researchers
have concluded.
But getting a patient’s CD4 count as high as possible and their HIV
viral load as low as possible is a good idea before they go under the knife.
Researchers conducted a retrospective study of 332 HIV positive and HIV negative
pairs of patients.
They found people living with HIV had the same overall rates of surgical complications,
including wound infection, need for repeat surgery, general post-operative
infection and wound splitting as HIV negative patients.
And people living with HIV did not require longer stays in hospital to recover,
nor more frequent post-operative visits to the surgeon.
Post-operative pneumonia occurred more frequently among the HIV positive patients,
but the number of cases was small: eight compared with one in the negative
group.
Twelve months after being out of hospital there were more deaths among the
HIV positive people compared with HIV negative patients (10:2), but the researchers
thought these deaths were not related to the surgery.
Interestingly, people living with HIV who had heart and lung surgery (19 cases)
seemed to do better than their HIV negative counterparts.
Having a viral load above 30,000 copies predicted a higher complication rate,
as did having a CD4 count below 50. Patients with between 50 and 200 CD4 cells
did no worse than those with higher CD4 cell counts.
This study is possibly the largest analysis of surgical outcomes for people
living with HIV in the modern HAART era comparing postoperative responses
in HIV positive and HIV negative people to a range of different operations.
• Arch Surg 2006;141:1238-1245
GSK halts work on experimental PI
British drug giant GlaxoSmithKline has cited problems in creating an oral
dosage of brecanavir as the reason why it halted work on its investigational
protease inhibitor.
Brecanavir had reached phase II testing and early results in treatment-naïve
and treatment-experienced patients were promising. The drug had appeared active
against some PI resistant virus.
People currently receiving brecanavir in clinical trials will be switched
to other therapies.
GSK said: “This decision has been taken as we have been unable to develop
a viable oral dosage formulation capable of delivering the desired drug levels
in patients with multi-drug-resistant HIV.”
Lipo drug looks good in late stage trial
Promising results from a phase III clinical trial of a drug for treating body
fat changes, have just been reported
TH9507 reduces abdominal fat, particularly visceral fat, without compromising
blood sugar control, making it potentially suitable for people with diabetes.
Visceral fat is found in the abdomen between the organs, and is a risk factor
for cardiovascular disease and type 2 diabetes.
The drug also increases muscle mass and improves the lipid (cholesterol, triglycerides)
profile, according to the report.
Manufactured by Theratechnologies, the drug is similar to the chemical in
the body that stimulates the production of growth hormone.
The trial looked at the safety and efficacy of giving two milligrams of TH9507
a day for 26 weeks and the drug’s long-term safety over 52 weeks.
The study enrolled 412 patients from 43 centres in the US and Canada.
The aim was to reduce visceral fat by eight per cent when compared with the
placebo group.
After 26 weeks, patients on TH9507 achieved a 15 per cent reduction in visceral
fat tissue and a 20 per cent difference compared with placebo.The drug was
well tolerated by all participants, the firm said.
A second phase III trial to confirm these results is required by regulatory
authorities and is due to starts shortly in North America and Europe in the
first part of this year.
PN contacted the company asking for details of European trial sites. As yet
we have not had a response.
