Compiled by Gus Cairns
Latest on new entry inhibitor resistance
Last month’s ICAAC Conference in Washington DC heard a lot about
the next class of HIV drugs likely to come along: CCR5 receptor inhibitors.
These drugs prevent a key stage in the infection process by stopping HIV attaching
to a molecule called CCR5 on the surface of certain cells.
However, experts have expressed fear that treatment with these drugs might
make HIV more virulent.
The conference heard how GlaxoSmithKline’s (GSK) entry inhibitor, 873140,
produced a 40-fold drop in viral load when given as the only HIV therapy for
10 days.
But until now there has been no data on whether this drug causes the virus
to mutate into a form (CXCR4 virus) that could attach to another molecule.
When this happens there is often a CD4 fall and progression to Aids.Data presented
found the CXCR4 virus was much more common in patients who’d ever had
CD4s under 100. One in five patients selected for the study had to be excluded
because they had some CXCR4 virus in their system already. Of 63 patients
given 873140, CXCR4 virus unexpectedly emerged in two patients.
In one, the CXCR4 virus disappeared again after the drug was stopped, but
the other patient still had 20 per cent CXCR4 virus in his system a year later.
He remains clinically well off-treatment, but has experienced a significant
CD4 count decline.
This study suggests patients who take CCR5 inhibitors should probably do so
before they experience low CD4 counts. It also shows careful tests must be
done to ensure patients with CXCR4 virus do not take it.
All-protease combo looks promising
The recent Glasgow Aids Conference heard some promising results on
so-called ‘double boosted’ protease inhibitors (PIs). In these
combos, two protease inhibitor drugs are taken together, with their blood
levels boosted by a pinch of a third, ritonavir. A presentation on boosted
saquinavir and atazanavir was the most significant. With these two drugs you
get more than two bangs for your buck because levels of saquinavir and, to
a lesser extent, atazanavir in the body are boosted above what you’d
expect.
Taking these two PIs could potentially be a useful drug regime for patients
with resistance to the other two main drug classes, nukes (NRTIs) and non-nukes
(NNRTIs). They may also be usefully combined with nukes in patients with moderate
resistance to PIs.
A German study called ATSAQ gave saquinavir/atazanavir/ritonavir as the sole
drug combo to 40 patients whose current regime was failing (average viral
load 3,700). They also had experience of previous PIs, including lopinavir/r
(Kaletra).
Seven months into the study, 85 per cent had a viral load under 400 and 60
per cent under 50, which are good results for such treatment-experienced patients.
Meanwhile, Marta Boffito, from London’s Chelsea and Westminster Hospital,
announced further research showing saquinavir was stored inside the cells
in people taking the ATSAQ combination.
This means it might be a very resistance-proof regime, maintaining more-than-adequate
fighting strength and able to last long in the body , so the odd late dose
is not disastrous.
However combining PIs can be unpredictable. Some taken together actually lower
each others’ blood levels. This happens if you combine lopinavir with
fosamprenavir, and the new PI tipranavir with most other PIs.
But very early results from Glasgow suggested that atazanavir might manage
the same ‘double-boosting’ trick with fosamprenavir. A case study
from Edinburgh suggested a tipranavir/indinavir combo might work too.
‘Minority of positive men have risky
sex’
Only a minority of HIV positive men who have sex with men (MSM) in the States
are engaging in sex most likely to pass on the virus, a new sex survey suggests.
Of 1,153 MSM who reported their last sexual encounters, only four per cent
had fucked someone without a condom who was HIV negative or might have been.
This survey provides a snapshot of sexual behaviour in US MSM and reveals
a lot about how HIV positive men try to avoid passing on HIV.
Researchers quizzed 2,419 HIV positive MSM in 16 states spread throughout
the US between May 2000 and December 2002.
Of the 1,923 whose sexual behaviour over the previous year was known, 31 per
cent reported they had been sexually abstinent.
Of the 1,177 who had sex, 37 per cent were monogamous with one partner throughout,
and 30 per cent said they had only had oral sex.
Sixty-eight per cent of the sexually active men, reported fucking, with 40
per cent reporting being ‘active’ at the last encounter. Of these
115 did not use a condom, and only 47 with a partner who was or might have
been HIV negative.
HIV positive men were only 60 per cent as likely to be ‘top’ with
guys who were negative as they were with other positive guys, and only 30
per cent as likely not to use a condom with them.
The term ‘MSM’ was used in this study because one in six men identified
as bisexual and one in nine as heterosexual - even though they had sex with
men.
• High-risk sexual behaviour by HIV positive men. US Centers for
Disease Control and Prevention.
Drug resistance ‘often over-stated’
Shocking statistics on HIV drug resistance do not necessarily
translate into widespread treatment failure, according to UK resistance expert
Dr Deenan Pillay.
Dr Pillay told the Glasgow HIV Conference that recent studies showing resistance
in three in four people with HIV in the UK were misunderstood.
These studies only revealed resistance in three in four people who had taken
a resistance test. These people are obviously more likely to have resistance.
By calculating resistance in the entire treated population instead, you actually
find only one in five patients on treatment has resistance.
And of some 22,000 people currently taking HIV treatment, no more than about
800 have resistance to all three classes of HIV drugs. These are the people
dependent on new drugs coming along.
People should also not be alarmed by the commonly quoted figure that a quarter
of transmitted HIV has some drug resistance.
Resistance defined in the test tube did not always translate into clinical
failure, Pillay said.
A stricter definition of resistance predicts that about one in 10 people catch
HIV with enough resistance to limit first-line treatment choices.
In another presentation, Mark Wainberg, from Montreal, Canada, emphasised
that if you caught resistant virus the resistance stays with you for life.
But drawing on his experience of six of his patients who had caught HIV, resistant
to all three commonly-used classes of drugs, he explained how the clinical
consequences were unpredictable.
One patient was ‘super-infected’ with a second strain of multi-drug
resistant (MDR) virus nine months after the first. This patient has failed
numerous regimes and now has a sub-200 CD4 count and is waiting for new options.
But MDR virus is usually less fit than non-resistant virus, and many people
with MDR virus maintain low viral loads.
Another of his MDR patients in the audience told how he had maintained a low
viral load off treatment for six years and considered himself a long-term
non-progressor.
medical notes
Circumcised men ‘strikingly’
less likely to have HIV
Circumcised men are 11 times less likely to have HIV than uncircumsised
men, according to a Kenyan study. Another Indian study found an eight-fold
reduction in HIV infection among circumcised men. Derek von Wissell, director
of Swaziland’s National Emergency Response Council on HIV/Aids, said
cicumcision should be looked at as a preventive measure as it was was “almost
as effective as a vaccine.”
Viral load lower in women on vitamins
A US study of women using complementary therapies found they were significantly
more likely to have a viral load under 1,000 than women who didn’t.
Sixty-one per cent using vitamins had a low viral load compared with 48 per
cent of non-users. But the survey of largely poor black women found vitamin
users had had more Aids-related illnesses. Vitamins might not have a direct
effect on viral load but might be taken by more treatment-experienced patients
who’d learned to look after themselves better.
Hep C protease inhibitor progress stalled
A protease inhibitor that works against hepatitis C has produced impressive
results, last month’s Gastroenterology journal reports. The drug produced
a 100- to 1,000-fold reductions in hep C viral load in 51 patients, regardless
of their stage of liver disease or the subtype of hep C virus. But fears about
toxicity has put the development of the drug BILN 2061 on hold pending long-term
animal studies after animals, given large doses for four months, developed
heart problems.
Truvada receives European approval
Truvada, Gilead’s fixed-dose combination pill of tenofovir and FTC,
received European marketing approval on 18 November. Approval follows data
presented to the ICAAC conference last month that showed FTC and 3TC were
equally effective. Early results also indicate the one-pill, once-a-day combo
might be a more potent nucleoside ‘backbone’ for HIV drug regimes
than AZT/3TC (Combivir).
Vaccine ‘could prevent 70 per cent of cervical
cancer’
A vaccine against the two most common types of cancer-causing human papilloma
virus (HPV) has been found to protect against 95 per cent of new infections
and 100 per cent of re-infections. HPV causes genital and anal warts, but
certain subtypes (16 and 18) are much more likely than others to cause cervical
and anal cancer. The VLP vaccine stops infection with these. Manufacturers
GlaxoSmithKline said: “Vaccination against HPV 16 and 18 could prevent
development of up to 70 per cent of cervical cancers worldwide.”
Doctors warn of ‘chlamydia with claws’
Doctors are warning gay men about a rare sexually transmitted infection that
can cause severe bleeding and inflammation in the lower gut. Ninety cases
of lymphogranuloma venereum (LGV) were recorded in gay men in the Netherlands
in 2003-4. LGV is caused by a variant of the bacterium that causes chlamydia
and is treatable by antibiotics. “You can get really sick with this,
but it doesn’t present like an STD, and neither clinicians nor patients
will be thinking of an STD,” said Dr Stuart Berman, chief of STD
epidemiology at the US Centers for Disease Control.
Septrin works for kids and super-bug
UNAIDS and the World Health Organisation have recommended all children with
HIV in developing countries should get the cheap antibiotic co-trimoxazole
(Septrin) after a Zambian study found it almost halved the risk of death.
The drug is familiar as an anti-PCP drug, but it’s not clear why the
children benefited. Meanwhile, another study has found Septrin works against
the community-acquired ‘super-bug’ MRSA (methicillin-resistant
staphylococcus aureus). This bug, normally only seen in
hospital settings, was reported as a sexual infection among gay men in the
US last year.
