Part 2 of our special report from the 12th Retroviruses conference.
Compiled by Anna Poppa
Fish oil tablets reduce high blood fats
Fish oil tablets are an effective treatment for HIV
positive people with abnormally high levels of a blood fat known as triglyceride,
a new study has found.
High triglycerides (hypertriglyceridaemia) can occur as a side-effect of HIV
treatment, and are a known risk factor for heart disease.
In the general population, fish oil has been shown to reduce high triglycerides,
and cut the risk of further heart disease in people who have already had a
heart attack. Their effect in people with HIV has not been so well studied.
The Maxepa trial recruited people on stable HIV treatment, with raised triglycerides
even after a 4-week dietary programme. Participants were randomly allocated
to two treatment groups; one which received 2g of fish oil three times a day,
and the other which received dummy capsules containing paraffin oil.
After eight weeks, triglyceride levels had returned to normal in 22 per cent
of those taking fish oil, and seven per cent of those taking the placebo.
Fish oil also reduced levels of cholesterol, another ‘bad’ blood
fat.
The main side-effect of treatment was diarrhoea, which occurred in 12-15 per
cent of people in each group.
Study exposes scale of HIV drug resistance
A UK study has presented new findings on the rate of drug resistance
in people starting three- or four-drug HIV combination therapy.
The UK Collaborative HIV Cohort (UK CHIC) provides information on the emergence
of resistance during the first six years of treatment, a relatively long follow-up
period for a study of this kind.
Taking HIV treatment using a HAART combination of three or four drugs delays
the emergence of drug resistance compared to the one- or two-drug combinations
previously used to treat HIV.
However, even in people who start HIV treatment with HAART, drug resistance
can still emerge if treatment is not able to control viral load.
According to the UK CHIC group, resistance to one class of HIV drugs had developed
in 27 per cent of people after six years.
Twenty per cent had resistance to two classes at this point, and four per
cent had resistance to all three main classes.
As tests for drug resistance have been incorporated into HIV care only relatively
recently, and tests do not detect the full range of resistant viruses a person
may be carrying, these figures are likely to be underestimates.
Once drug resistance has been detected, it is likely that further resistance
will accumulate in people who continue to take treatment. Of those patients
who developed resistance to one HIV drug class after starting HAART, 21 per
cent had resistance to all three main classes four years later.
Resistance was less likely to emerge in people who started treatment with
a HAART combination that included a boosted protease inhibitor like lopinavir
than one including a non-nucleoside like nevirapine or efavirenz.
It must be stressed this study was not designed to make a strict comparison
between the effects of different HIV treatments - there may have been differences
between the patients prescribed these two forms of treatment which could not
be accounted for by the researchers.
More options for reversing body fat loss
New trial results have provided further evidence that lost body fat
may be slowly restored, through switching HIV treatments.
Body fat loss (lipoatrophy) is linked to use of HIV drugs in the NRTI class,
most particularly d4T or AZT.
Two studies have already shown the benefits of switching from these drugs
to either abacavir or tenofovir.
Now two further trials indicate that changing to a combination which excludes
NRTIs altogether is another option.
In the first study, people with body fat loss taking a d4T- or AZT-containing
combination were switched either to a completely new combination of lopinavir/ritonavir
plus nevirapine, or switched their d4T or AZT for abacavir and maintained
the other drugs they were taking.
Both treatment groups gained abdominal fat during the initial six-month study
period, though subcutaneous fat (that sits under the skin rather than around
organs) increased more in the group who switched to lopinavir/ritonavir plus
nevirapine, the NRTI-sparing combination.
In a second study, people who switched from a protease inhibitor plus NRTIs
to a combination of lopinavir/ritonavir and efavirenz (an NRTI-sparing combination)
gained peripheral fat over a 48-week study period. People who instead switched
to efavirenz plus two NRTIs continued to lose peripheral fat after the change
in treatment. In this trial, however, switching to the NRTI-sparing combination
increased the risk of viral load failure.
UK doctors demand new HIV drugs
Doctors from six of the UK’s largest HIV treatment centres have
warned that a significant minority of their patients risk running out of effective
HIV treatments. Without new, easily tolerated drugs that are effective against
drug resistant HIV, these people face an uncertain prognosis, they said.
A recent report from the UK Collaborative HIV Cohort (UK CHIC) group said
38 per cent of people who started HIV treatment at one of their clinics between
1996 and 2002 have now taken drugs from the NRTI, PI and NNRTI classes.
Of these, 15 per cent have experienced viral load failure on each of these
three classes, and so may be expected to have developed considerable drug
resistance.
The collaborative includes people with HIV attending six clinics in the south
east of England: Chelsea and Westminster Hospital, King’s College Hospital,
Mortimer Market Centre, St Mary’s Hospital, Royal Free Hospital, and
Brighton and Sussex University Hospital.
More positively, the group found that key markers of immune and virologic
status had improved over time amongst the whole group of patients.
This is likely to be a reflection of improvements in HIV treatment and care
that have occurred in recent years.
In 1996, 38 per cent of patients who had received HIV treatment had a CD4
count below 200, a threshold which signifies an increased risk of HIV-related
illnesses.
By 2002, this had fallen to 13 per cent.
Low CD4 counts were more common, however, in people who had experienced virologic
failure on all three HIV drug classes.
In 2002, 33 per cent of patients who fell into this category had a CD4 count
below 200 cells.
Depo injections unaffected by HIV drugs
Women
on HIV treatments also taking the injectable contraceptive DMPA (Depo-Provera)
are unlikely to suffer adverse interactions, a new study suggests.
Depo-Provera is a progesterone-based contraceptive used largely for its convenience
as it is given as a single injection that lasts 12 weeks.
However, it is processed via an enzyme system in the liver also used by many
HIV treatments, particularly protease inhibitors and non-nucleosides.
A recent American study recruited women whose HIV treatment combination included
either efavirenz, nevirapine, or nelfinavir, and measured how blood levels
of these drugs were affected by a dose of DMPA.
There was no evidence of significant drug interactions in any direction, indicating
that DMPA can be taken with any one of these HIV drugs. Further studies are
planned to test the effects of taking DMPA with newer HIV treatments.
medical notes
Efavirenz failure in black people
A US study has found higher rates of treatment failure in black people on
efavirenz. Black
people were twice as likely as white people to stop efavirenz within the first
year. Poor adherence was a more common reason for the drug to be stopped than
side-effects.
Further study is required to explain these findings.
The study follows reports that efavirenz may reach unusually high levels in
the blood of black people compared to white people.
Efavirenz interaction with buprenorphine
A drug interaction study has found that efavirenz
reduces blood levels of
buprenorphine, a treatment
for heroin addiction.
However, this reduction did not appear to result in the development of opiate
withdrawal symptoms. This suggests that buprenorphine may be preferred to
methadone as a treatment for opiate-dependent people
taking efavirenz.
An interaction between efavirenz and methadone has been noted to cause withdrawal
symptoms.
New NNRTI ineffective in salvage
Capravirine, an unlicensed NNRTI undergoing clinical study in people with
HIV, has failed to provide any benefit in a trial
involving volunteers with
previous NNRTI experience.
The findings are a disappointment, as test-tube studies had indicated that
the drug was effective against NNRTI-resistant virus. Trial participants received
either a placebo or one of two capravirine doses, together with nelfinavir
and two NRTIs. All had previously taken an NNRTI-containing HIV treatment
combo, but had not used protease inhibitors. After 48 weeks, there was no
difference in viral load response between patients who received capravirine
and those receiving the dummy pill.
Warning on tenofovir & ddI
Gilead Sciences and Bristol-Myers Squibb have issued a warning on the risks
of using their NRTIs, tenofovir
and ddI, together. The pharmaceutical companies say the drugs should not be
taken at the same time, particularly by people with high viral load and low
CD4 counts, unless strictly necessary. Patients who have no alternative but
to take the two drugs should be monitored carefully for early signs of both
virologic failure, and side-effects linked to ddI.
Rapid HIV progression ‘rare but real’
An analysis of 400 people, whose date of HIV-1 infection is known, has shown
one per cent had
progressed to Aids within a year of infection, and two per cent by two years.
The observation that rapid progression to Aids does occur, though not commonly,
was reported following the recently-publicised case of a New York man who
progressed to Aids within four to twenty months of picking up multidrug-resistant
HIV
(see treatment news in April’s PN).
Heart disease risk worsening in people with
HIV
Factors that predict an increased risk of heart disease are growing in frequency
among people with HIV, according to a recent report from the DAD study, a
large, international trial exploring the long-term safety of HIV treatment.
Between 2000 and 2003, the proportion of DAD participants with at least two
established risk factors for heart disease (older age, diabetes, previous
heart disease, high blood pressure, high
cholesterol) increased from 34 per cent to 42 per cent. Smoking however, was
less common in 2003 than in the previous year, and the use of drugs to reduce
high blood fats had increased.
