Compiled by Robert Fieldhouse
Hormone supplement has no immune-boosting
effects
A
natural steroid hormone supplement previously thought to boost the immune
system in people with HIV has no such properties, new research suggests.
Dehydroepiandrosterone (DHEA), a precursor to testosterone and estrogen, is
sold in internet pharmacies as a supplement with a wide range of health benefits.
Previous research has indicated that DHEA may boost the immune system, mood,
quality of life, muscle mass and bone density.
Some preliminary data even suggested DHEA reduced HIV reservoirs, places the
virus hides even if we have an undetectable viral load. This made some think
DHEA might usefully be taken with currently available antiretroviral therapy.
This time US researchers conducted a randomised, double-blind, placebo-controlled
study in 40 HIV positive people with undetectable HIV viral loads on antiretroviral
therapy. This kind of study is considered the most rigorous type.
Participants were randomly assigned to receive either DHEA or placebo for
12 weeks. Thereafter all participants received DHEA for 12 weeks.
They regularly monitored patients’ virus reservoirs, immune function,
hormone levels, body weight and composition, and quality of life.
Levels of infectious HIV in virus reservoirs went up in people on DHEA, although
there was no significant change in HIV viral load levels.
DHEA supplementation taken by people with fully suppressed HIV was associated
with improvements in quality of life. But the supplement appeared to have
no beneficial affect on viral load, the immune system, or lean muscle mass
or bone density.
The researchers concluded there was no evidence to support using the supplement
routinely in addition to antiretroviral therapy.
• AIDS Research & Human Retroviruses 23(1): 77-85. January 2007.
Life expectancy estimates differ greatly
Canadian researchers have calculated a 20-year-old starting HIV therapy
between 2002 and 2004 could only expect to live about 24 more years. This
is lower than 35 years predicted recently by Danish researchers for a 25-year-old
diagnosed today with HIV in Denmark.
Canadian researchers calculated death rates and life expectancy in 2,238 previously
untreated people who started treatment between January 1993 and September
2004. They looked at the causes of death in the periods 1993-1995, 1996-1998,
1999-2001, and 2002-2004 and estimated life expectancy for a person starting
therapy in each.
In 1993-1995, 15 per cent of people died within one year of starting therapy.
This decreased to 6.1 per cent in 2002-2004. Estimated life expectancy increased
from 9.1 years in 1993-1995 to 23.6 years in 2002-2004. That means a 20-year-old
beginning therapy in 2002-2004 could expect to live only to about 44 years
of age.
People starting treatment in 1993-1995 were almost three times more likely
to die compared with those starting in 2002-2004. People starting two or more
antiretroviral drugs had more than twice the chance of surviving as those
starting one drug therapy.
• AIDS 2007;21:685-692
Cervical cancer vaccine may cut HIV replication
New research suggests non-infectious particles used in anti-cervical cancer
vaccines may also inhibit HIV replication in the test tube.
Cervical cancer is usually caused by human papiloma virus (HPV). The vaccine
uses a version of the virus that has been rendered non-infectious to stimulate
the body to become immune to HPV.
Researchers in the US found that HIV replication was suppressed by the vaccine.
Further study showed the cytokine (chemical messenger) IL-27 was responsible
for this supression.
IL-27 is known to be a potent anti-cancer cytokine. Further investigation
should define the exact mechanism of the cytokine’s anti-viral effect.
Further studies looking at how IL-27 reduces HIV may pave the way for a new
kind of HIV therapy in the future.
• Blood 2007;109:1841-1849
Herbal meds linked to ditching ARVs
People living with HIV in Uganda are more likely to quit HIV therapy if they
also use traditional herbal medicine, new research has found.
The findings suggest that the integration of traditional healers into modern
medical practice needs to be handled cautiously.
The World Health Organisation has reported between 60 and 70 percent of African
people use traditional healers as their first line approach to health care.
With access to antiretrovirals slowly improving across Africa, many people
may be switching between traditional healers and western medicine.
Researchers from Uganda’s Makerere University studied 686 patients at
two large treatment centres in Kampala. They found one in five patients had
interrupted therapy.
Cost was the most reported reason why people stopped treatment (40 per cent),
followed by negative side effects (20 per cent) and unreliable medication
supply. Others quit because they were tired, depressed, felt better or were
away from home.
People who used a traditional healer were twice as likely to give up the drugs.
However, rather than shunning traditional healers, the researchers suggest
the solution is to work more closely with them.
Seventy per cent of those who modified their combination said side-effects
were the main reason. Unmarried people, those on therapy for more than three
months, patients who started treatment in 2004 or earlier and individuals
taking more than two pills per day were all more likely to have altered their
therapy.
Over the past two years, Uganda has significantly stepped up its antiretroviral
rollout. According to the government, HIV drugs have reached more than 80,000
people. But between 150,000 and 200,000 Ugandans need the life-prolonging
medication now or they will die.
High CD4 counts help to tolerate chemo
People with CD4 counts above 200 who develop lung cancer tolerate chemotherapy
and are almost as likely to survive after cancer treatment as people without
HIV, according to new research.
A team of US researchers looked back through their hospital’s tumour
registry to see if there were differences in outcome between HIV positive
and HIV negative people who had been diagnosed with lung cancer since 1996.
They identified 34 people with lung cancer and were able to show that the
people with HIV with advanced lung cancer survived almost as long as HIV negative
people.
The researchers argued that having a high CD4 count (either naturally or through
using HIV treatment) was the key reason why people with HIV were almost as
likely to survive as long as HIV negative people. People living with HIV,
the researchers argue are good candidates for treatment for lung cancer. J
Thorac Oncol, 2007;2.
Second in new class of HIV drug enters trials
A
second drug of a new type of HIV meds has just entered clinical trials. This
drug could prove more resilient than the first against the development of
HIV resistance say developers Panacos.
The first maturation inhibitor, bevirmat (PA-457), already in phase II trials,
has already led to the development of a second, PA-040, which has now entered
phase I trials. Both aim to prevent the HIV maturing into infective particles
that can subsequently spread around the body.
HIV not only reproduces rapidly but also mutates easily. This leads to people
with HIV having many different forms of the virus in their body. Some of these
mutations can lead to drug resistance. When HIV emerges from a human cell
it is not yet fully mature or infective. A protein called HIV protease cuts
up the so-called GAG complex, HIV’s protective coating, into its constituent
parts, allowing it to then infect further CD4 cells.
Protease inhibitors such as saquinavir or atazanavir work by preventing HIV
protease from working. However, mutations in the protease protein can prevent
the drugs from working.
Beviramat and PA 040, by contrast, disables HIV by binding to the GAG complex
and destroys the protein sheild which protexts HIV’s genes. This complex
is much less affected by mutations than protease.
This is why Panacos hope that resistance will be less of a problem for this
class of drug.
Double-dose tenofovir may combat nuke-resistant
HIV
A small study has suggested that it may be possible to treat people with HIV
who have some resistance to drugs like d4T (Zerit) and AZT (Retrovir, Combivir,
Trizivir) with double the dose of tenofovir (Viread) to reduce virus levels.
Tenofovir is usually taken at a dose of 300mg once a day. At the start of
this trial which included ten people who had never taken tenofovir before
but who had developed some resistance to older nukes, trial participants’
viral loads averaged around 5,000 copies and their CD4 counts averaged 407
cells.
After four weeks of treatment with double-dose tenofovir, added to their existing
failing treatment, HIV viral load had decreased to an average of 1,500 copies
and CD4 counts had increased by an average of 109 cells.
By taking double the dose of tenofovir, participants blood levels of the drug
also doubled. One patient developed Fanconi’s syndrome, a kidney disorder
where electrolytes and nutrients are not properly absorbed back into the body.
No serious side effects were seen during the four week study. Further studies
are required to monitor the long-term effects of taking double the dose of
tenofovir on kidney function.
This small study provides proof that the concept of taking twice the dose
of tenofovir may suppress HIV that has some resistance to nukes, but the researchers
warned that the regimen should only be considered within a controlled clinical
trial in salvage therapy. Larger studies are now needed.
J Med Virol 2007; 79: 105-110
Generic ‘d’ drug made available
to poz kids in US
The first generic powder version of the nucleoside analogue ddI (Videx)
has been licensed in the US for use in children living with HIV.
The powder for the 10mg/ml oral solution is packaged in 2g and 4g containers.
HIV protein helps kill cancer cells
A protein derived from HIV helps to kill cancer cells, according to new research.
This has the potential to be a promising avenue for cancer treatment, exploiting
existing mechanisms such as an HIV protein to deliver a cancer drug.
US researchers discovered the HIV-1 TAT protein kills pancreatic, lymphoma
and melanoma cancer cells and the effect was greatest if combined with radiotherapy.
So far the approach has only been studied in mice, but researchers are confident
this could lead to a novel approach to cancer therapy.
• Ann Surg Oncol 2007.
Scientists discover natural barrier to HIV
Researchers
have discovered that cells in the mucosal lining of the penis, vagina and
anus produce a protein that ‘eats up’ invading HIV.
Enhancing the activity of this protein could be a potent new way to curtail
HIV transmission.
Called Langerin, the protein is produced by Langerhans cells which form a
web-like network in skin and mucosa. This network is one of the first structures
HIV confronts as it attempts to infect its host.
For decades the common wisdom was that HIV easily enters and infects Langerhans
cells but this research now casts doubt on that notion.
Researchers found Langerin was able to attack viruses from the surrounding
environment thereby preventing infection.
Since generally all tissues on the outside of our bodies have Langerhans cells,
researchers think the human body is equipped with an antiviral defense mechanism,
destroying incoming viruses.
The finding may explain in part why HIV is relatively inefficient at being
transmitted.
When HIV comes in contact with genital mucosa, its ultimate aim is to hijack
and destroy CD4 cells. But these are relatively far away in lymph tissues,
so HIV uses nearby Langerhans cells as ‘vehicles’ to migrate to
them.
The finding is exciting for many reasons, not the least for it potential in
HIV prevention and the race to find topical microbicides gels to protect against
HIV infection. Choosing compounds that allow Langerin to continue to work
its magic could enhance a microbicide’s effectiveness.
• Nature 4 March Online
Nuke which works after 3TC/ FTC failure in development
Encouraging phase II study results involving an experimental NRTI (nuke) have
just been released. Initial three-week results suggest the investigational
drug apricitabine is effective against HIV with the M184V mutation, known
to cause high-level resistance to 3TC (Epivir) and FTC (Emtriva).
Two doses of apricitabine (600mg or 800mg twice-daily) were compared with
continuing failing 3TC (150mg twice-daily) therapy in treatment-experienced
people. All participants had evidence of the M184V mutation, documented by
drug resistance testing.
Sixty patients were recruited and an analysis has been done on the first 47
(33 of whom were taking one of the two doses of apricitabine).
Patients who received apricitabine achieved on average an almost ten-fold
reduction in viral load after 21 days treatment compared to an almost minimal
change in patients maintained on 3TC therapy.
No serious side effects to the drug were reported and the drug will now continue
into phase III trials. Expect results to be presented later this year.
Kaletra may blunt action of anti-cholesterol
drug
An
anti-cholesterol drug previously thought safe to use with protease inhibitors
has been found to interact with lopinavir/ritonavir (Kaletra).
Unlike some anti-cholesterol drugs, the statin rosuvastatin was previously
thought to have no significant interaction with protease inhibitors.
However, recent research found Kaletra (lopinavir/ritonavir) increased levels
of rosuvastatin in the blood.
Surprisingly, this appeared to to blunt rosuvastatin’s effect on total
and low-density lipoprotein (LDL) cholesterol. Levels of Kaletra in the blood
were unaffected by rosuvastatin.
Many protease inhibitors alter the way the liver breaks down statins, often
resulting in significantly increased levels of statins in the blood.
But it was previously thought rosuvastatin had no significant interactions
with protease inhibitors because they are broken down in different ways.
The researchers urged caution when using rosuvastatin with any protease inhibitor.
• Abstract 564, 14th CROI, Feb, 2007, USA
Lower CD4 on therapy increases cancer risk
People with lower CD4 counts on HIV therapy have a higher risk of developing
liver, kidney, heart problems and non-Aids defining cancers, new research
suggests.
It’s long been known that if we have a low CD4 cell counts despite taking
antiretroviral therapy we remain at risk of Aids-defining opportunistic infections.
But our risk of developing non-Aids defining illnesses in such circumstances
was less clear.
The FIRST study randomised 1,397 people who had never taken HIV treatment
before to either a PI-based, NNRTI-based or triple-class combination.
Researchers divided fatal and non-fatal illness into four groups: liver diseases
such as cirrhosis; heart-related illnesses such as heart attack, stroke; kidney
problems such as renal insufficiency; and 32 non-Aids-defining cancers including
skin, anal and lung, but excluding non-Hodgkin’s lymphoma and Kaposi’s
sarcoma.
Researchers discovered a person’s risk of non-Aids defining illnesses
decreased by around 16 per cent for every 100 cell increase in their CD4 count.
The risk of Aids-defining events fell by 43 per cent for every 100 cell increase
in their CD4 count.
This figure was reached after taking into account latest viral load and CD4
count, age, gender, prior Aids diagnosis, hepatitis co-infection and injecting
drug use.
The results suggest people are not developing non-Aids-defining illness solely
as a consequence of living longer thanks to antiretroviral therapy.
Instead it suggests that people whose CD4 counts don’t recover so well
on HAART are still more likely to get sick.
These findings are likely to lend support to treatment strategies that focus
on maximising CD4 counts, such as starting therapy well before they fall below
200 (see PN 48 for more).
• Abstract 37, 14th CROI, Los Angeles, 2007.
Don’t OD on FTC
A warning has been issued against people taking FTC (Emtriva) with other similar
nucleoside analogues.
People taking FTC should not take it in combination with Truvada which also
contains FTC. People taking FTC should also not take it in combination with
3TC or 3TC-containing combos, which include Combivir, Kivexa and Trizivir.
The US Food and Drug Administration has included its advice in an updated
patient information sheet for FTC.
