Our doctors follow strict guidelines when starting people on HIV drugs, but what happens when the ‘preferred’ first-line therapy is not right for you?
Words Robert Fieldhouse
Images Craig Hewitt
Current
HIV treatment guidelines from the British HIV Association (BHIVA) recommend
which drugs should be offered to most people starting HIV therapy (see box,
right). But one size does not fit all and in
recognition of this, the guidelines also recommend alternatives in the protease
inhibitor (PI) and NNRTI classes.
No drug is right for everyone; what works for one may not be as well tolerated
by another. Pre-existing personal factors like our risk of heart disease or
history of psychiatric illness can influence which drugs are most likely to
be suitable. And we never really know how we will tolerate a drug until we
try it.
Efavirenz: depression and metabolism
If you have experienced depression in the past, some doctors may be reluctant
to
prescribe efavirenz as it is sometimes
associated with psychiatric side effects such as depression and anxiety. These
side effects are more common in people with a previous history of psychiatric
illness. Under these circumstances, doctors are likely to give nevirapine
as an alternative.Some people metabolise efavirenz slower than others due
to a particular genetic variation common among black Africans. Someone with
this variation may be more likely to develop efavirenz-related psychiatric
side effects. If you feel you may be at increased risk of psychiatric symptoms
with antiretroviral drugs, discuss the alternatives with your doctor. As we
live longer with HIV, it’s right we think about our blood lipids, cholesterol
and triglycerides, and how these impact upon our risk of developing heart
problems. Some HIV drugs may add to the risk of developing heart disease so
it is always worth discussing this with your doctor. Read more about lipids
and cholesterol in Heart of the Matter (page 42).
Which NNRTI is more lipid-friendly?
A large trial of 1,216 people living with HIV compared the non-nucleoside
reverse transcriptase inhibitors (NNRTIs) nevirapine and efavirenz. People
treated with nevirapine for 48 weeks experienced a greater increase in HDL
or ‘good’ cholesterol than those on efavirenz. In addition, nevirapine
treatment resulted in a significantly improved total cholesterol to HDL-cholesterol
ratio. This is associated with a reduced risk of heart disease.
Should I avoid protease inhibitors (PIs)?
Not necessarily. Last year researchers showed that elevated blood lipids caused
by protease inhibitor treatment are best treated with either pravastatin (Lipostat)
or bezafibrate (Bezalip) rather than by switching the protease inhibitor to
an NNRTI. In the study people either switched their PI to the NNRTI nevirapine
or efavirenz or stayed on their PI and added one of the lipid-lowering drugs.
After 12 months the average reduction in triglyceride levels was 25 per cent
for people who switched to nevirapine, nine per cent for people who switched
to efavirenz; 41 per cent for people adding pravastatin; 47 per cent for people
who added bezafibrate.Clearly, people who stayed on their PI and added lipid-lowering
drugs had significantly greater decreases in their triglyceride levels than
those changing treatment.
A similar response was seen for total cholesterol. Average levels declined
by 27 per cent for patients switching to nevirapine; 10 per cent for those
switching to efavirenz; 46 per cent for individuals taking pravastatin and
38 per cent for patients taking bezafibrate. One in five who switched to an
NNRTI achieved normal triglyceride levels compared to half of those taking
lipid-lowering drugs. Similar findings were observed with reductions in total
cholesterol either with a switch to NNRTI therapy or using lipid-lowering
drugs. If your protease inhibitor is fighting your virus well, it may be possible
for you to stick with it and simply add a lipid-lowering drug.
Are some PIs more lipid-friendly?
There is strong evidence that fosamprenavir (taken twice-daily boosted with
ritonavir) is more lipid-friendly than the most widely prescribed PI, lopinavir/ritonavir.
Although blood fats tend to increase with fosamprenavir, the increases are
fairly modest. HDL ‘good cholesterol’ levels also increase with
fosamprenavir, so the HDL/LDL cholesterol ratio remains fairly stable. This
phenomenon, also seen with the NNRTI nevirapine, is not commonly seen with
other protease inhibitors.
As yet, we don’t know whether this will translate into actual ‘cardioprotective’
effects associated with higher HDL cholesterol levels when they occur naturally.
Saquinavir also has a fairly benign lipid profile compared to other PIs. In
a 48-week study where it was studied against lopinavir, triglycerides increased
by an average of 29 per cent if people were treated with lopinavir, compared
to a six per cent decrease if they were taking saquinavir. In another study,
the metabolic impact of saquinavir was similar to that of the NNRTI efavirenz.
When choosing your medication it is worth discussing potential lipid advantages
to different drugs with your doctor.
The BHIVA guidelines
on starting HIV therapy
Guidelines recommend a first-line HIV combination consisting of two
nucleoside analogues with one NNRTI or one protease inhibitor. Drugs shown
in bold are the favourable option because of their proven effectiveness.
Nucleoside analogues (choose 2)
Abacavir/3TC (Kivexa)
AZT/3TC (Combivir)
Tenofovir/FTC (Truvada)
ddI
+
NNRTIs (choose 1)
Efavirenz (Sustiva)
Nevirapine (Viramune)Protease inhibitors (choose 1)
Lopinavir/ritonavir (Kaletra)
Saquinavir/ritonavir (Invirase 500)
Fosamprenavir/ritonavir (Telzir)
Drug alternatives: the patients’ verdicts
We spoke to three people living with HIV to find out why they opted to take
an alternative to the BHIVA preferred drugs.
Saquinavir
Side effects tend to be the same regardless of gender, although women seem
to clear saquinavir from their systems slower, further increasing its potency.
Consequently, increasing numbers of women use it during pregnancy.
Paul, 35, recently switched to the new formulation of saquinavir (Invirase,
500mg).
“I was reluctant to go back on a protease inhibitor as I started therapy
in 1997 with saquinavir when it was dosed as 18 tablets a day and taken with
high-fat food and grapefruit juice to increase absorption. I switched to nevirapine
as soon as it became available as it was so much simpler to take.
“I knew one day I might have to go back on a PI. I was happy with nevirapine
but had developed resistance to it. My doctor switched me to lopinavir but
it gave me really bad diarrhoea. When he suggested saquinavir I was shocked
as I thought of the old days, but taking it today is not like then; I take
just two tablets twice a day alongside one ritonavir, morning and night with
breakfast and dinner. It couldn’t be easier. I’ve been on it now
for five months and my CD4 hit 850 just before Christmas.”
Fosamprenavir
Chris, 42, started therapy 10 years ago. He tried a few combos before his
viral load finally went undetectable. But his CD4 count never seemed to budge
higher than 150. He’d taken ddI alongside hydroxyurea with nevirapine
until six years ago when he switched to the PI amprenavir (taken boosted with
a small dose of ritonavir). He took eight tablets twice a day.“Just
getting them down was a problem,” says Chris. Like saquinavir, amprenavir
was re-formulated, significantly reducing the number of tablets he needed
to take.
Chris switched to fosamprenavir and tolerated it really well. He attended
the lipodystrophy clinic at the Harrison Unit at London’s St Thomas’
Hospital where he was advised to increase his exercise and watch his diet.
Sticking with his combo has paid dividends; his CD4 now fluctuates between
700 and 900 and he’s been
undetectable for years.
Nevirapine
Brian, 38, has taken the NNRTI nevirapine for eight years. It is still his
first combo, though he has switched around the nucleosides after d4T gave
him peripheral neuropathy. More recently he ditched Combivir as the veins
in his arms and legs were becoming very prominent and he was losing fat from
his face.
“Nevirapine seemed simple compared to PIs; one tablet in the morning,
one in the evening, roughly 12 hours apart. I haven’t had side effects:
it’s the drug I’ve been happiest with. I don’t see any reason
why I won’t be able to continue with it for years.”
