Compiled by Gus Cairns
New anti HIV drugs coming along fast
The HIV drugs ‘pipeline’ is looking healthy, with good news about
forthcoming protease inhibitors (PIs), the Retroviruses conference heard.
In addition, there is a powerful non-nucleoside (NNRTI) further away, and
the first-ever human trials of two completely new classes of drugs.
Boehringer Ingelheim’s PI tipranavir performed better than expected,
suppressing HIV in 41 per cent in a group with PI resistance, compared with
19 per cent on other PIs.
It has even unexpectedly worked on HIV thought to be resistant to the drug.
Tipranavir is already available on extended release and, if all goes well,
will be licensed in the US soon and in the EU later this year.
Another PI, TMC114, did even better with 47 per cent of 397 PI-resistant people
achieving a viral load under 50, including five out of 13 people resistant
to all other known drugs.
It also produced a low rate of side-effects. TMC114 goes into a larger clinical
trial later this year and could be in the pharmacy by 2007.
Further along is TMC278, a new NNRTI. It is one of a group of chemicals called
DAPYs, which can outmanoeuvre HIV’s attempts to become resistant by
changing its shape. It has only just been given to people with HIV: a seven-day
trial produced an average 20-fold viral load drop, and the smallest dose,
25mg once daily, produced the best results.
Finally, two completely new kinds of drug were given to people with HIV for
the first time.
L-870810 is an integrase inhibitor. Companies have been trying to develop
this class of drug for ten years. The new drug, given twice-daily to patients,
produced a 60-fold drop in viral load. Unfortunately, due to toxicity concerns
in animals, this drug is going to be dropped, but another candidate, L-870812,
is close behind.
And PA-457 is a maturation inhibitor. It was discovered by chance in chemicals
from birch trees a few years back. Just one dose was given to HIV positive
people, producing around a three-fold viral load drop.
The risk of having a heart attack rises by 17 per cent for every year on HIV
therapy, a large study presented at the Retroviruses conference showed.
The DAD study, which monitors heart attacks in 23,441 people on HIV treatments,
found 277 heart attacks, just over a quarter of them fatal.
This rate is still low, representing just one heart attack a year per 277
people. But two more years of data collection from the study show the risk
has continued to grow.
The DAD study has not divided people up into drug classes to see if any are
more likely to cause heart trouble, but about two-thirds of participants had
taken a protease inhibitor.
Researcher Dr Jens Lundgren told a press conference that the risk of taking
HIV therapy was similar to, or slightly greater than, smoking.
He said: “The bad news from the DAD study is that the cumulative risk
has continued to grow since 2003. HAART approximately doubles risk. Smoking
also approximately doubles the risk and nearly half of our study population
are smokers. If they stopped smoking the risk would go down almost to what
it was before.
“To put this into context, however, in 1995 before HIV combination therapy
came along, the mortality rate among my patients was 23 per cent a year. Now
it’s 1.5 per cent a year.”
Experts split over New York ‘supervirus’
The much-publicised case of a New York man who caught HIV resistant to almost
all drugs and which rapidly led to Aids, divided eminent experts at the Retrovirus
conference.
New York health commissioner Thomas Frieden who issued the original press
release on the apparent ‘super-bug’ told the conference: “This
case is a wake-up call... to men who have sex with men, especially those who
may use methamphetamine [crystal]”.
The man had reported having had multiple sexual partners and taking crystal
meth.
Veteran Aids journalist Laurie Garrett supported the commissioner’s
decision to issue a public health alert.
He said: “In 1981, too many scientists ignored six cases of a strange
pneumonia in gay Californian men. That was Aids, which has now killed more
than 25 million people.”
HIV physician Dr James Braun warned the conference that transmission of treatment-resistant
HIV “was a disaster waiting to happen”.
But other HIV specialists criticised Frieden. Co-discoverer of HIV Dr Robert
Gallo said: “One case is not enough to warrant a public health alert.
We’ve already heard past claims about superviruses that turn out to
be nonsense.”
The virus resistance pattern was unusual, and a search of the national database
only found one similar virus in a San Diego patient.
But reports that this was the person who passed on the virus to the New York
man proved false.
It also became clear the case was not as ‘unique’ as first suggested.
Canadian expert Dr Julio Montaner revealed he had dealt with two similar cases
in 2001, and they hadn’t turned into an epidemic of super-Aids.
HIV prevention advocate Julie Davids questioned why the media were concentrating
on the irresponsibility of some gay men instead of cuts to HIV prevention
services.
Dr David Ho, conference chair and a physician involved in the case, said the
virus was 36 per cent fitter than non-resistant HIV - very unusual for drug-resistant
HIV, which normally reproduces poorly.
However, the virus was not impossible to treat. The patient has since responded
to the drug T-20 and efavirenz.
One crucial fact remains unknown: when did the patient catch the virus?
A previous negative test in 2003 suggests he caught it between two and 20
months before the symptoms started.
If he caught it six or more months ago, it is very worrying; the man’s
immune system should have settled down after initial infection. But if caught
more recently, then what we are probably seeing is an unusually devastating
initial infection.
Immunologist Daniel Douek said even ordinary HIV infections caused far more
severe damage to CD4 cells in the first few weeks of infection than thought,
with 80 per cent of the cells in the intestines wiped out.
Even with HIV drugs, the body never completely recovers from this assault,
he said.
The New York patient had a variety of HIV called CXCR4 or T-tropic virus,
which is rarely transmitted but when it is, causes much worse damage.
It’s starting to look like the New York patient had an unusually intense
initial infection, but it does not represent the beginning of a new ‘plague’.
HIV treatment activist Mark Harrington told PN: “I think Frieden had
to make his announcement. If this does turn out to be a cluster of cases everyone
would have asked why we weren’t told.”
US public health expert Harold Jaffe told the conference: “If lack of
fear has become a driver of this epidemic, should cases like this be used
to scare people? I personally don’t think so. But we need to remind
people of realities of HIV.”
Drugs delay transmission in monkeys
A study to see if giving tenofovir to rhesus monkeys could prevent them getting
HIV ended in disappointment when the drug delayed, but failed
to prevent, infection. The experiment found that risk of infection from a
single squirt of semen up the bum was reduced from 50 to 15 per
cent. But because the doses were three to five times the maximum likely viral
load in human semen, investigators urged that they be allowed to continue
human trials
HAART has its limits
Four different studies presented at Retroviruses found that, although some
people do better, the maximum CD4 gain in patients taking anti-HIV therapy
for years averages out at 350 cells. These studies found CD4 counts in most
patients stopped rising after four to five years. Largest gains were seen
in people with the lowest initial counts, suggesting the body has a set limit
to CD4 recovery in HIV infection.
Uganda: deaths reduce HIV prevalence
A study from Uganda found
that falls in the HIV rate in the population during the last ten years
were almost entirely due to more people dying of Aids, not behaviour change.
Eighty per cent of the downward trend was due to more people dying, with the
other 20 per cent due to increased condom use, while the annual rate of new
infections did not change at all. Far from being abstinent or faithful, Ugandans
from the Rakai district actually had more sexual partners in 2004 than in
1994. Prevention campaigners have drawn opposing conclusions from these findings.
Some say condoms are the only thing that has stopped the HIV rate getting
worse; others that it shows that providing them only encourages more sex.
HPV vaccine could stop warts and cancers
A vaccine against the human papilloma virus (HPV), which causes genital warts
and cervical and anal cancer, could prevent 90 per cent of genital warts and
70 per cent of cervical and anal cancers, the conference was told. The vaccine,
made by Merck, protects against the two most common types of wart virus and
the two most likely to cause cancer. A two-type vaccine made by GSK has already
finished trials, producing results nearly as good. The vaccines would have
to be given to teenagers before they started having sex and would not cure
HPV infection.
Sexually-transmitted hep C is common
A study of 2,900 Swiss with HIV has found a high rate of infection with hepatitis
C. The patients had no other risk
factors like needle-sharing and appear to have got the virus through sex.
About one in 500 people, gay and straight, got the infection a year, but the
rate went up to one in 140 in gay men who had unprotected sex. In comparison,
about one in 50 gay men in London gets HIV a year.
Coke and crystal are biggest gay HIV risk
Using coke or crystal meth is the biggest single risk factor for becoming
HIV positive among US gay men, the conference heard.Grant Colfax, of San Francisco
health department, said coke or crystal use contributed 29 per cent of the
overall risk of becoming positive, and being passive in bareback sex, 28 per
cent. Another study from San Diego found crystal users were six times less
likely to use condoms.
