Compiled by Robert Fieldhouse
Size matters for hepatitis C treatment in
co-infected
Using a person’s weight to select the ribavirin dose in pegylated interferon/ribavirin
improves treatment outcomes for people co-infected with HIV and hep C.
Using weight as a guide makes a sustained virological response (SVR) to treatment
more likely. SVR is usually regarded as evidence that hepatitis C has been
cured.
This was the main finding of the PRESCO trial presented at the 8th International
Conference on Drug Therapy in HIV Infection.
Each trial participant received 180mg of pegylated interferon alfa-2a (Pegasys)
each week with a daily dose of either 1,000mg ribavirin if the patient weighed
less than 75kg or 1,200mg if they were heavier.
At total of 192 patients with the hardest to treat hep C virus, genotypes
1 or 4, took 48 weeks of treatment while 45 took it for 72 weeks.
Ninety-six with genotypes 2 or 3, the easier types to treat, took it for 24
weeks and 56 for 48 weeks.
Sustained virological response rates were 49.6 per cent for all patients;
34.1 percent for genotypes 1 and 4, and 72.4 per cent for genotypes 2 and
3.
Professor Vincent Sorriano said it had proved difficult to persuade patients
to lengthen their treatment period largely due to tolerability issues. He
said study results were “hampered by voluntary withdrawal”.
Extended treatment conveyed additional benefit. SVR results for patients with
genotypes 1 and 4 were 53 per cent for patients on treatment for 72 weeks
and 82 per cent for patients with genotypes 2/3 on 48 weeks’ treatment.
A third discontinued treatment - 8.2 per cent due to side effects.
Around 15 per cent had their interferon dose reduced due to side effects and
about 20 per cent of patients had their ribavirin dose reduced.
Anaemia is the side-effect that usually limits the amount of ribavirin someone
can take. Nine participants stopped treatment by week 48 because of anaemia.
One person committed suicide during the trial.
Researchers also analysed the early virological response rates, which usually
indicates the likelihood of eventual treatment success.
At week 12, 60 per cent of people with genotype 1 had a virological response.
This compares with 34 per cent in Roche’s large co-infection study,
APRICOT, where patients received the same drugs but ribavirin was given at
a standard 800mg daily dose.
Abstracts PL13.1 & 314. 8th International Congress on Drug Therapy in
HIV Infection, Glasgow.
Zinc supplements fail to improve runs
People taking the nucleotide analogue tenofovir do not appear to develop body
fat loss associated with treatment with drugs in the nucleoside analogues
class.
Researchers used sensitive x-ray scans to measure limb fat content over time
to see if long-term treatment with tenofovir reduced body fat.
A total of 602 participants were randomised to receive either tenofovir or
d4T (Zerit) alongside 3TC (Epivir) and efavirenz (Sustiva). Treatment with
d4T is particularly associated with the loss of body fat.
People who started therapy with d4T got the chance to switch to tenofovir
after three years of treatment with d4T.
Typically, after switching from d4T to tenofovir, patients regained a kilo
of lost limb fat over a two years period. The switch to tenofovir from d4T
was also associated with small but significant improvements in fasting triglycerides
and total cholesterol.
There were no significant change in kidney function and minimal loss of bone
mineral density over five years among the people on tenofovir. Some experts
have previously expressed concern that these side effects may occur after
long-term treatment with tenofovir. This was not the case in this study.
Abstracts 28 & 82 8th Lipodystrophy workshop 2006
HIV blocker now available on expanded access
scheme
An international expanded access programme for Pfizer’s investigational
CCR5 antagonist maraviroc will begin in early 2007.
Maraviroc is the first of a new class of antiretrovirals called chemokine
antagonists which block HIV from using the CCR5 co-receptor to gain access
to CD4 cells.
In people with less advanced HIV the virus predominantly uses the CCR5 receptor
to gain entry into CD4 cells. These people are said to have CCR5-tropic virus.
As HIV progresses, the virus starts to switch to an alternative receptor;
CXCR4. Maraviroc will only be available for patients who have the less advanced
CCR5-tropic virus.
Research presented at the 2006 World Aids Conference showed that maraviroc
had a modest but positive effect on CD4 counts in people with advanced HIV
infection. However, it did not reduce viral load significantly.
A new test called a tropism assay can detect if you have CCR5-tropic virus.
Pfizer plans to submit licensing applications for maraviroc in the US and
Europe shortly.
Major boost for microbicide drive
Pharmaceutical company Gilead has given the green light for international
agencies to use their HIV drug in a special gel to prevent the spread of HIV.
Under the royalty-free licence, key prevention agencies will use the HIV drug
tenofovir (Viread) to develop a microbicide for women to apply before having
sex.
Microbicides could provide the key to HIV prevention, especially in countries
where women are unable to successfully negotiate condom use with their partners.
Gilead signed the agreement at the end of last year with the International
Partnership for Microbicides (IPM) and CONRAD, part the US Agency for International
Development.
The agreement enables the agencies to develop, manufacture and distribute
the tenofovir-based microbicide in up to 100 resource-limited countries.
The US National Institutes of Health’s HIV Prevention Trials Network
has already evaluated tenofovir gel in early stage clinical trials.
Dr Zeda Rosenberg, IPM chief executive, said they were grateful for Gilead’s
leadership in developing microbicides for women.
The two agencies will also investigate tenofovir in combination with other
antiretroviral drugs.
More women than before, in every world region, are living with HIV, according
to the latest UN report on the global Aids epidemic.
There are now around 17.7 million women living with HIV, a million more than
in 2004.
“Collaboration within the microbicide field is crucial to our eventual
success,” said Dr Henry Gabelnick, executive director of CONRAD.
“It is through public-private partnerships and the combined expertise
of organisations like CONRAD and IPM that we will get an effective microbicide
quickly to the women who urgently need this technology.”
Cipla launches three-in-one once-daily HIV pill
Indian generics manufacturer Cipla has developed a copycat version
of Atripla, the new co-formulated once daily HIV combo.
Atripla contains efavirenz, tenofovir and FTC and is manufactured by Gilead,
Bristol Myers Squibb and Merck.
The branded drug was launched last year in the US and is expected to be launched
this year in Europe.
Cipla’s generic equivalent, Viraday, was launched in India at one tenth
of the price of the branded version. Cipla is proceeding to register Viraday
in various parts of Africa.
In 2001, Cipla launched the first fixed-dose combo Triomune, combining d4T,
3TC and nevirapine in one pill taken twice a day.
It offered the drug at US $350 per patient per year, against a global US price
of $10,439. Triomune is now one of the most frequently prescribed HIV treatments
in developing countries.
Radiotherapy reaches the parts other treatments
cannot reach
Researchers are reporting a major breakthrough in HIV therapy by using
radiotherapy to kill cells which remain infected by the virus despite antiretroviral
therapy.
Tests carried out in mice in the US showed radioactive antibodies not only
destroyed HIV-infected cells, but also sought them out.
A similar approach is being developed to treat cancer that only targets cancer
cells. The tests showed that radiotherapy worked in combating HIV in the liver,
spleen and thymus.
But researchers are unsure whether radio- immunotherapies can reach HIV in
all parts of the body, especially the brain.
Researchers will next use the radiotherapy to help people who don’t
respond to current treatments. Human clinical trials may begin in the next
two years.
Aids, past, present and future
During a recent visit to the UK, one of the world’s leading HIV doctors
said HAART was the “biggest victory in medicine in the last 30 years”.
Professor John Bartlett, of Johns Hopkins School of Medicine in Baltimore,
was in the UK to address the British Association of Sexual Health (BASH) on
medical advances in treating HIV over the last quarter of a century.
The professor also led a question and answer evening with HIV doctors and
nurses.w
Professor Bartlett’s new book, Medical Management of HIV Infection,
is published by Johns Hopkins University. MJF
• www.hopkins-hivguide.org
Pharmacos collaborate against hep C
Two drug companies have teamed up to develop protease inhibitors effective
against hepatitis C.
Abbott Laboratories and Enanta Pharmaceuticals announced their agreement to
co-develop the drugs at the end of last year.
Enanta’s work on hep C protease inhibitors complements Abbott’s
work in hep C polymerase inhibitors. Test tube studies indicate the potential
for the development of an oral medicine. An estimated 170 million people worldwide
are infected with hepatitis, with a high rate of HIV co-infection.
First in new drug class gets green light
A named patient programme for MK-0518, an integrase inhibitor (II)
currently in late stage clinical development by Merck, began towards the end
of last year.
Integrase is an enzyme HIV uses to insert its DNA into CD4 cells. IIs prevent
this happening by stopping the enzyme working properly.
To be eligible to access the drug you need to be currently on a failing regimen
with resistance to at least one drug in each of the three classes of oral
antiretrovirals (NRTI, NNRTI and PI) and be at risk of clinical or immunologic
progression. To find out more about access to the drug your doctor needs to
contact the medical information department at Merck.
MK-0518 should not be used with the investigational NNRTI TMC-125 (see right)
until the results of an interaction study are presented.
Next generation non-nuke available to named patients
A new NNRTI drug is now available in the UK as part of a named patient programme.
The drug, TMC-125 (Etravirine) is currently in late stage development by pharmaceutical
manufacturer Tibotec.
TMC-125 is a ‘next-generation’ NNRTI. This means that it appears
it will be active against strains of HIV resistant to existing licenced NNRTIs,
though this is dependant upon the number of mutations that have developed.
Phase 3 clinical trials (DUET 1 and 2) in treatment- experienced patients
are fully enrolled and should report findings later this year.
The named patient programme provides access for people living with HIV who
need the drug to construct a viable treatment regimen.
To be eligible for the drug you must have already been prescribed an oral,
licensed drug from each of the following three classes: NRTIs, NNRTIs, and
PIs, and must have received at least two PI-based regimens.
Alternatively, your doctor could make a case for access if you are intolerant
of other meds.
Your doctor will need to make a request for access to the drug to the medical
information department at Tibotec.
Malaria fuels spread of HIV
High
rates of HIV infection in sub-Saharan Africa can be partly explained by the
presence of malaria, according to Kenyan researchers.
Malaria speeds up HIV transmission rates because it significantly increases
the viral load of people living with HIV. Having a high viral load makes it
more likely that we can transmit HIV to our sexual partners.
People living with HIV are also far more susceptible to malaria.
Scientists investigated the malaria theory with a modelling exercise after
observing that HIV spread more rapidly in Kisumu, near Lake Victoria in Kenya,
than could be explained by risky sex alone. Malaria is highly prevalent in
Kisumu and can increase the amount of HIV in the blood tenfold.
HIV’s weakening of the immune system has also fuelled a surge in adult
malaria rates.
Researchers estimated that tens of thousands of HIV infections, five per cent
of the total, and millions of malaria cases, could be attributed to co-infection.
They concluded that the two diseases should be treated together to reduce
HIV transmission.
Science December 8 2006
Clarification
In Treatment News Positive Nation 126 (p46) we stated that researchers had
given a study group 200mg (milligrams) of selenium. This would have been a
toxic dose and should have read 200µg (micrograms). Likewise, in PN127,
Uncomplimentary Therapies (p50) we made a similar error regarding the dosage
of selemium.
Boosted PIs prove equally effective in head
to head
Saquinavir
is as effective in the management of HIV as lopinavir, a current gold-standard
treatment, according to a new study.
Both drugs, which are given with ritonavir to boost their levels, were tested
as a combination with fixed dose combo tablet Truvada (tenofovir/FTC). After
24 weeks, they were shown to be equally effective at lowering viral load.
In the study, 337 people starting HIV therapy for the first time were given
either 500mg of saquinavir plus 100mg of ritonavir, or 600mg of lopinavir
with 100mg of ritonavir, twice a day.
Most participants had fairly advanced HIV, with viral loads averaging 150,000
copies and CD4 counts of around 125 cells. Almost a third had CD4 counts below
50.
Data from 150 patients who reached week 24 showed similar proportions treated
with saquinavir and lopinavir achieved an undetectable HIV viral load; 69.4
and 75.3 per cent respectively.
CD4 cell count increases were also similar in both groups.
The data, presented at the 8th International Congress on Drug Therapy in HIV
Infection, also found saquinavir was more lipid-friendly.
By week 24, patients on lopinavir were more likely to develop greater increases
in their triglycerides compared with those treated with saquinavir.
Patients taking lopinavir were more likely to report nausea and diarrhoea
compared with those on saquinavir. Around a fifth in each group discontinued
treatment during the study.
Critics would argue that the total number of patients included in the analysis
are not sufficiently large, nor have they been followed for long enough to
confirm that these two are equivalent.
8th International Congress on Drug Therapy in HIV Infection. Glasgow. Abstract
2.5.
Treatment breaks double death rates
People who choose to take breaks from HIV therapy are doubling their risk
of dying, according to a large treatment-interruption study
A study of 5,500 people from 33 countries, published in the November’s
New England Journal of Medicine, suggests ‘drug holidays’ are
dangerous for people with HIV.
The rate of HIV progression was more than twice as high in patients who took
antiretrovirals in cycles followed by breaks as the rate in people who stayed
on therapy.
The leading causes of death were cancers, cardiovascular disease, substance
abuse and various opportunistic infections associated with Aids.
In the drug holiday group, several developed diseases like bacterial pneumonia,
fungal infections and Aids-related cancers.
“Quite unexpectedly, our results show that interrupting therapy increases
the risk of non-Aids-related events,” said lead researcher Dr Wafaa
El-Sadr, of New York’s Harlem Hospital.
Several previous studies had suggested drug holidays might be OK for patients
who appear to be doing well.
Some people stop taking their HIV medicines because of side effects or toxicity.
Others stop taking them when their CD4 counts have risen and when their viral
load becomes undetectable.
However, both these strategies can be dangerous leading inevitably to higher
viral loads and lower CD4 counts.
Leading HIV doctor, Professor Brian Gazzard, said the message remains simple:
“Keep taking the tablets.”
Common wart cream also effective against anal cancer
A common treatment for anal warts may also be effective against related cancerous
changes in the anus, a study has found.
Anal warts, which are caused by human papillomavirus (HPV) can develop into
AIN (anal intraepithelial neoplasia). This in turn can lead to anal cancer.
Imiquimod, which is used to treat warts, can help men avoid surgery if they
develop AIN.
Researchers looked at 28 HIV positive gay men with confirmed AIN and high-risk
HPV types that might lead to cancer. They applied the cream three times a
week over a 16 week period, and were asked to stop receptive anal intercourse.
77 per cent of those who stuck to the regimen experienced a complete clinical
recovery, although long-term clearance was rare.
Arch Dermatol 2006;142:1438-1444.
