TWO-AND-HALF years ago, one 38-year-old gay Canadian man with HIV might have
considered himself relatively fortunate. The strain that had infected him was a
mild one and, eight years after infection, without drug treatment, his immune
system was still in good order.
Then he met someone and began a promising relationship. But almost
immediately his condition deteriorated鈥攁nd fast. In just six months, the
number of CD4 white blood cells in his circulation halved. Levels of HIV in his
blood rose fivefold. And worse, he didn鈥檛 respond to powerful antiviral drug
therapy.
An investigation by doctors at Ottawa General Hospital revealed that he had
caught a more virulent and drug-resistant strain of HIV from his
partner鈥攖he first documented case of 鈥渟uperinfection鈥� by HIV in humans.
The doctors, who announced the news at last month鈥檚 annual Conference on
Retroviruses and Opportunistic Infections in San Francisco, said the incident
should serve as a warning that safe sex is important in a relationship even if
both partners are HIV-positive.
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But the case has far more profound implications for scientists and health
workers battling the AIDS pandemic. If infection by live HIV doesn鈥檛 protect
against infection by another strain of the virus, what hope is there that a
vaccine made from weakened or inactivated viruses, or HIV substitutes, can offer
protection?
In other words, the Canadian case seems to have booted the prospect of an
AIDS vaccine even further into touch. Some eminent researchers question whether
an effective one-shot vaccine is even feasible. So should the time and resources
spent in search of the perfect vaccine instead be spent on other ways of
preventing AIDS?
One researcher alarmed by developments is Frances Gotch, an HIV vaccine
specialist at the Imperial College School of Medicine at the Chelsea and
Westminster Hospital in London: 鈥淲hat this means for a vaccine is terrible,鈥� she
says. 鈥淲e鈥檝e got to go right back to the drawing board. If people are becoming
superinfected when they鈥檙e relatively well and have got antibodies and CTLs
[cytotoxic T lymphocytes, a specialised kind of immune cell] against HIV, this
bodes extremely badly for the production of a vaccine. It鈥檚 exceedingly bad
苍别飞蝉.鈥�
The head of the US鈥檚 AIDS research programme shares the concern. Anthony
Fauci, also director of the National Institute for Allergy and Infectious
Diseases, points out that a vaccine is not as potent in stimulating an immune
response as the disease it is meant to protect against. 鈥淚f this replicating
virus can鈥檛 do it, then a vaccine is going to have a tough time doing it,鈥� he
says.
The situation would seem less desperate, Fauci says, if the Canadian case of
superinfection was a one-off, or at least a rarity. Gotch has just received a
big grant from the Wellcome Trust to test whether this is the case. This summer,
she will study HIV-positive couples in Uganda in which each partner is infected
by a different strain of HIV. The team hopes to measure the ease with which
superinfection occurs in these relatively healthy couples.
Jonathan Angel of Ottawa General Hospital, who documented the Canadian case,
also suspects the phenomenon is very common. Many of the doctors who were at the
San Francisco meeting believe they have seen it too, but they haven鈥檛 been able
to confirm their suspicions.
Worryingly, Angel鈥檚 research so far suggests that the two virus types in the
superinfected man are not hugely different. Although he notes that even in
people with a mild strain of HIV, who appear to have normal immune systems,
changes might have occurred that make infection by another strain more
likely.
The first documented superinfection follows close on the heels of another
blow to AIDS vaccine research. One of the leading candidates for an effective
vaccine is being developed by researchers in Oxford and Nairobi, based on their
study of Kenyan prostitutes who appeared immune to the virus. These women were
not infected but had large numbers of CTLs targeting HIV. It seems they had
fought off HIV infection on many occasions, and in the process became
鈥渋mmunised鈥� against the virus.
But in January, 快猫短视频 revealed that after leaving the sex
industry, six of these women had become infected
(29 January, p 5). One member
of the Oxford team, Sarah Rowland Jones, described the news as dismaying. The
vaccine, which contains internal parts of the virus, is intended to create a big
CTL response in people who receive it. But even if the vaccine can do this, the
latest news suggests it would offer only temporary protection.
The sponsor of the vaccine, the International AIDS Vaccine Initiative, has
put a brave face on it. Its chief scientific adviser, Jaap Goudsmit of the
University of Amsterdam, says the Oxford vaccine strategy could still play a
part in the production of combined vaccines. 鈥淚 don鈥檛 think an effective vaccine
will be developed in one trial,鈥� agrees Jose Esparza, coordinator of the newly
announced joint WHO/UNAIDS vaccine initiative. 鈥淲e will learn from the first
trials and the vaccine will improve.
鈥淢y message is: don鈥檛 wait for a vaccine, work for a vaccine. We must carry
on testing vaccines in clinical trials even if, by the time they鈥檙e ready for
testing, the science seems to have moved on. Even a 50 per cent effective
vaccine might be used as part of a preventive package.鈥�
Other leading authorities are less sanguine. 鈥淔or me, the six Kenyan women
becoming infected was even worse news than the superinfection,鈥� says Jean Paul
Levi, director of the Cochin Institute for Molecular Genetics in Paris and head
of the vaccine programme of France鈥檚 National AIDS Research Agency. 鈥淚t
suggested that for cell-mediated immunity against HIV, you must have continuous
别虫辫辞蝉耻谤别.鈥�
This means that rather than just a one-off shot, people would need
repeated immunisation鈥攕omething beyond the means of developing
countries.
Besides vaccines intended to provoke a CTL response, researchers have also
been working on ones that produce a humoral response, in which the body makes
antibodies against parts of the envelope surrounding the virus. But this has not
enjoyed great success either.
A key problem is the variability of HIV. Very little of HIV鈥檚 surface is
identical in all strains of the virus, and so far scientists have been unable to
develop vaccines that make the immune system attack these 鈥渃onserved areas鈥�.
It鈥檚 not clear how, or even if, scientists will be able to accomplish this feat.
鈥淲e don鈥檛 know if we can do it,鈥� Levi admits. 鈥淚n the next three to four years
we will probably learn if it鈥檚 possible.鈥�
And we shouldn鈥檛 forget the double whammy posed by HIV, Gotch says. When the
virus infects someone, their immune system does provide a strong challenge. But
unlike, say influenza, HIV is not cleared in a matter of days because it sneaks
into our DNA and hides there. So even if a vaccine does stimulate the immune
system to attack the elusive conserved areas, that doesn鈥檛 guarantee protection
against chronic infection.
Some groups, notably Thomas Lehner鈥檚 team at Guy鈥檚 Hospital in London, have
shown that encouraging the generation of immunity on mucosal surfaces such as
the vagina and rectum, where infection is likely to occur, offers some hope. But
administering such vaccines has proved difficult, and how long their protective
effect lasts is unclear.
Instead, perhaps we should shift resources to simpler methods of preventing
infection. Effective vaginally applied virucides would allow women to protect
themselves, for example, while treating other sexually transmitted diseases
would reduce the number of HIV infections. 鈥淭hese are cheap compared with
vaccine development,鈥� says Angel. 鈥淚 wouldn鈥檛 like to be the one who has to
decide how the dollars are spent.鈥�
Fauci is adamant that both approaches are vital. He says the news from Kenya
and Canada is 鈥渟obering鈥�. But, like Esparza, he thinks that via a series of
steadily improving products, the world will eventually have an effective
vaccine鈥攖hough he won鈥檛 predict when, other than to say that it will be
鈥渋n less than 25 years鈥�.
The social and economic destruction that HIV will wreak in the developing
world between now and 2025 is almost unimaginable. 鈥淭o control this epidemic we
need a vaccine,鈥� says Levi, 鈥渂ut we鈥檙e not sure we can get one. I suppose we
don鈥檛 want to think about that.鈥�