Compiled by Robert Fieldhouse
Nuke-sparing combo suppresses HIV but raises
lipids
Using
nukes (NRTIs, see below) over a long period may lead to side effects such
as fat loss and peripheral neuropathy. That is why researchers are increasingly
keen to study the effectiveness of HIV combos that exclude nukes.
Regimens that combine non-nukes (NNRTIs) and PIs can elevate blood fats, but
the PI atazanavir (Reyataz) is associated with fewer lipid elevations than
others.
Researchers studied 61 people starting therapy for the first time with one
of two doses atazanavir/ritonavir (300/100 or 400/100mg) plus 600mg efavirenz
(Sustiva) but no nukes. Most were men (85 per cent), in their late thirties.
The average CD4 count at the time of starting therapy was 305 cells.
Three quarters (75 per cent) in the 300/100mg atazanavir arm and 67 per cent
in the 400/100mg arm achieved HIV viral loads below 400 copies.
Sixty-three per cent and 61 per cent, respectively, achieved a viral load
below 50 copies while the average increase in CD4 cell count was 271 cells
and 250 cells, respectively.
Insomnia, rash, diarrhoea, and dizziness were the most common side effects.
Twelve patients discontinued the study prematurely, two of them due to side
effects.
Increases in triglycerides, total cholesterol and LDL-cholesterol, with robust
increases in HDL-cholesterol, were seen in both groups.
Thirteen per cent of those treated with the lower-dose of atazanavir and 40
per cent on the higher-dose experienced serious bilirubin rises indicating
liver toxiticity.
The researchers concluded that both atazanavir/ritonavir/efavirenz regimens
were “generally safe and well tolerated” and demonstrated potent
antiretroviral efficacy through 48 weeks.
But they noted lipid increases were greater than those seen in most previous
studies using the same drugs.
Because both ‘bad` LDL cholesterol and triglycerides rose along with
‘good’ HDL cholesterol, the researchers felt that long-term implications
for cardiovascular health could not be assessed from this study.
Abstract H-1057 ICAAC 2006
Tenofovir beats d4T on fat loss
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
Most hospitalisation of positive people due
to drug side effects
Hospital stays among HIV positive people are increasingly due to side effects
rather than opportunistic infections, according to a Spanish study.
The single clinic study ran over the last seven years. Researchers analysed
1,981 consecutive hospital admissions in 1,581 people living with HIV. Almost
half were on antiretroviral therapy.
Side effects were the main or secondary reason for 141 (seven per cent) of
patients being admitted, with liver toxicity accounting for one third of admissions.
Eighty per cent of the liver toxicity occurred in people co-infected with
hepatitis C.
All had favourable outcomes after hospitalisation except one who had had prior
end stage hep C- related liver disease and liver failure after starting therapy
with a protease inhibitor.
Aids Research & Human Retroviruses 22(9):825-829, 2006
Gene may increase vulnerability to severe
non-nuke liver damage
Genetics may play a major role in determining who is likely to get
severe, life-threatening liver problems when taking non-nukes.
Two small studies looked at liver-related toxicity in people taking nevirapine
(Viramune) and efavirenz (Sustiva).
Severe and in some cases fatal liver damage, particularly in the first 18
weeks of treatment, occurs in around one to five of people treated with nevirapine.
People co-infected with hep B or C are at greater risk.
A quarter of patients on nevirapine experiences liver enzyme elevations without
developing hepatitis while asymptomatic liver elevations occur in around eight
per cent of people treated with efavirenz.
Some people metabolise drugs less effectively by an enzyme known as cytochrome
p450 in the liver and throughout the body by an enzyme called P-glycoprotein
which flushes drugs out of cells into the gut.
Researchers have identified gene variations as being associated with both
lower and higher risk of liver toxicity with non-nukes.
They say the particular gene variation needs to be studied in larger groups
of people taking non-nukes alongside other predictors of HIV drug toxicity.
These predictors include a group of genes known as the human leukocyte antigen
system, associated with an increased risk of toxicity to HIV drugs such as
nevirapine or abacavir (Ziagen).
It is hoped it will eventually be possible to screen people before starting
therapy to see if they have the genetic variations that put them at high risk
of developing liver problems.
Clinical Infectious Diseases
2006;43:779-782 & 2006;34:783-786.
New combo offers hope to treatment experienced
Up to 95 per cent of people treated with the HIV fusion inhibitor T-20 plus
an integrase inhibitor can achieve undetectable levels of HIV, according to
T-20’s manufacturer Roche.
This compared with 60 to 70 per cent achieving an undetectable viral load
after taking Merck’s integrase inhibitor MK-0518 without T-20.
These results were from a 24 week phase II study of MK-0518 in treatment-experienced
patients with viral resistance to protease inhibitors.
“Such response rates have never been achieved in clinical trials of
HIV patients living with drug-resistant virus,” Roche said in a press
statement.
Warning over spiralling rates of TB
TB
cases in England, Wales and Northern Ireland have increased sharply, according
to new official figures.
The Health Protection Agency said cases of tuberculosis had risen by 10.8
per cent, from 7,321 cases reported in 2004 to 8,113 in 2005.
Dr John Watson, head of the agency’s respiratory diseases department,
said: “Levels of TB have been increasing year on year since the late
1980s. This is, however, the largest increase we have seen in any one year
since 1999.”
A majority of cases (43 per cent) are in London but the north-west also saw
cases rise from 588 in 2004 to 757 in 2005. In the East Midlands there were
443 cases in 2004 and 556 in 2005, and cases in the east of England rose from
395 to 483. However the north-east and Northern Ireland saw cases decline
while Wales remained static.
Dr Watson said the largest increase was seen among patients not born in the
UK, up from 4,696 in 2004 to 5310 in 2005.
But figures showed only 22 per cent of these non-UK born patients in 2005
arrived in the UK during the past two years.
“This suggests the increase is not a result of a large number of individuals
arriving recently with TB. Rather it is a combination of TB disease developing
in individuals who have been infected for some time and new infections acquired
in the UK.
“Increased travel to other countries where TB is common also contributes
to the figures,” he said. He reiterated that levels of TB in the UK
born population remained stable.
Stubborn CD4s with suppressed HIV may spell
trouble
Some people starting HAART achieve full viral load suppression but,
despite therapy, do not see their CD4 cell rise above 200 cells.
Canadian researchers wanted to find out if these people were at greater risk
of developing clinical symptoms of HIV infection, which may include persistent
enlarged lymph nodes, fatigue, weight loss, night sweats, bone pain and repeated
bacterial, viral or fungal infections.
They looked at a group of people living with HIV who started therapy between
August 1996 and September 2003. They divided participants into two groups,
according to whether or not their CD4 count on treatment rose above 200 cells.
A third did not attain CD4 counts of at least 200 cells within a year of starting
therapy. Ten of the 97 patients with CD4 counts below 200 cells, and 17 of
those with CD4 counts of 200 cells or higher, developed clinical events during
the 21 months of follow up. These events happened at an average 2.2 months
after starting therapy.
The researchers concluded there was an increased number of clinical events
in the first year of therapy in patients who achieved complete viral suppression
but failed to attain CD4 counts greater than or equal to 200. The increased
risk of clinical events remained if CD4 counts failed to rise above 200 after
one year.
People whose CD4 counts fail to rise above 200 should discuss it with their
doctor to see whether switching to an alternative treatment would be beneficial.
Abstract H-1403 ICAAC 2006
US approves new atazanavir tablet
US drug firm Bristol-Myers Squibb has received a license to market
a single pill version of its once daily protease inhibitor atazanavir.
The tablet can replace the two 150mg capsules, commonly taken with ritonavir.
European licensing of the new formulation expected soon.
Merck acquires promising new PI
Pharmaceutical company Merck and Co has acquired a new experimental protease
inhibitor that requires no ritonavir boosting and may be active against highly
protease inhibitor-resistant HIV.
The drug called PPL-100 may prove as potent a booster of other protease inhibitors
as Abbott’s ritonavir. Though the studies are at the earliest stage
in humans, the drug appears a good candidate for once-daily dosing.
Abstract H-253, ICAAC, 2006
Good news for kids exposed to HIV drugs in
womb
Babies
who remain HIV negative but who are exposed to HIV drugs in the womb appear
to suffer no damage to the way their brains develop.
Use of HIV drugs during pregnancy combined with other careful clinical management
means rates mother-to-child transmission in the UK have fallen to below one
per cent.
Researchers evaluated early brain development in 63 HIV negative children.
Thirty-nine were born to women living with HIV and 24 to HIV negative women
in the control group.
Half the women taking HAART were using recreational drugs such as cocaine
or the heroin substitute methadone, compared with only 12 per cent of women
in the control group.
Researchers suspected that use of these substances had a greater impact on
the child’s neurological development than exposure to HAART in the womb.
HAART use by pregnant women may lead to mitochondrial toxicity; neural tube
defects have been reported among babies exposed to nukes in the womb.
And studies have shown babies born to women living with HIV are more likely
to be born prematurely.
The researchers found the babies of women living with HIV were less able to
carry out simple tasks such as feeding themselves, but after the researchers
further subdivided the women by recreational drug use, these differences were
lost.
Pediatrics 118 (4):1139-45, 2006
Brits ignorant of hep B threat
A
new campaign has been launched to improve diagnosis, care and prevention of
hepatitis B.
The Department of Health estimates some 180,000 people, 0.3 per cent of the
UK population, are chronically infected with hepatitis B.
Each year 7,700 new cases of chronic hep B are diagnosed but only around 1,500
people receive treatment. Left untreated hep B can lead to serious liver disease,
including cirrhosis and liver cancer.
Public awareness of the disease is low. A recent survey of over 2,200 adults
revealed 86 per cent lacked a complete awareness of the infection.
More than half (60 per cent) did not know that hep B was preventable by vaccination,
while 40 per cent did not know that treatments existed.
Professor Arie Zuckerman, chair of the Hepatitis B Foundation UK, called for
the Department of Health and NHS chief executives to bring the UK into line
with most other European countries by introducing universal vaccination against
hep B.
“We also need to improve public health education and provide better
facilities for the treatment of the disease,” he added. Current estimates
suggest it costs the NHS between £26 and £380 million annually
to manage hepatitis B.
New drug combo shows promise
An investigational protease inhibitor (PI) taken in combination with a new
generation non-nuke and other antiretrovirals is effective in people with
resistance to more than one PI. Researchers looked at safety and treatment
response in 12 people taking TMC-114 with 100mg ritonavir (TMC-114/r) and
other HIV drugs, including the investigational next generation NNRTI TMC 125
over 24 weeks.
Patients were multi-class-experienced with resistance to three drug classes.
They took 600/100mg TMC-114/r twice daily plus a new 200mg formulation of
TMC125 once daily plus nukes (NRTIs), with or without the fusion inhibitor
T-20.
Six had already taken the recently licensed PI tipranavir (Aptivus) together
with T-20; while three were using T-20 for the first time.
At the start, participants’ CD4 cell counts averaged 75 cells while
key protease-inhibitor resistance mutations averaged four.
When secondary mutations were also counted, the total averaged 11. Participants
had an average of two non-nuke resistance mutations, meaning efavirenz and
nevirapine would be unlikely to work
Of the 12, one completed 16 weeks and 10 completed 24 weeks at the time of
the analysis. At week 24, nine of the 10 achieved an HIV viral load below
40 copies while the average CD4 count increase was 113 cells.
The researchers concluded the combination of TMC-114/r and TMC125 was well
tolerated and showed impressive short-term efficacy against three-class resistant
HIV. Further studies are ongoing.
Abstract H-1000. ICAAC 2006
Patients give lopinavir tablets thumbs up
US patients who switched from the old twice-a-day Kaletra capsule to the new
once daily version overwhelmingly prefer the new formulation.
Kaletra (lopinavir/ritonavir), a protease inhibitor, is currently available
in two tablets twice a day. But doctors can now offer once-daily lopinavir/ritonovir
to some carefully selected patientss.
Forty-one per cent reported a significant improvement in no longer having
to take the drug with food. Patients reporting severe diarrhoea fell from
12 to three per cent with the new tablet and tolerability appears improved
with 84 per cent describing it as ‘great’ or ‘very good’.
Adherence increased from 93 per cent to 97 per cent with the new tablet. More
than one in ten said that they had missed doses with the old formulation in
a bid to avoid side effects.
Schrader S et al. Poster. 8th Lipodystrophy workshop
