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Sunday, 7 July, 2002, 14:00 GMT 15:00 UK
Aids: The medical progress
Long term prospects for HIV treatments look bright

People living with Aids in developed countries should receive some good news later this year, when a new type of anti-retroviral drugs is expected to come onto the market - the first since 1995.

They're called fusion inhibitors. Unlike existing drugs which stop the virus reproducing, fusion inhibitors stop it getting into human cells in the first place.

They will add to existing treatments but researchers are also pursuing another, entirely different approach to drug therapy.

Anti-retroviral can slow the progress of the disease
Rather than interfering with HIV, the idea is to rebuild the immune system which the virus wrecks.

HIV progressively infects and destroys immune cells called CD-4 cells - and immune therapy, as it's called, stimulates the body to make more of these cells.

Several different drugs are under investigation, including interleukin-2 or IL-2 which increases the CD-4 count.

Janet Darbyshire Director of the Medical Research Council's Clinical Trials Unit in London says: "What the big trials which are now on-going are trying to find out is whether that increase in CD-4 translates into clinical benefit. In other words, if you haven't done anything to the virus itself, is that still going to delay disease progression and prolong life, which is the ultimate goal."

Vaccine trials

Neither fusion inhibitors nor immune therapy are likely to make much impact in the developing world, simply because of cost.

But a vaccine would. Altogether there have been around 30 trials of HIV vaccines in humans; but only two are what's called phase three trials, the large-scale studies which prove whether it works or not.

These two trials both involve a vaccine called AIDSVAX - we'll be hearing the final results next year.

There have been indications that it's effective; but some scientists believe the product is too simple to stand much chance of working.

"This vaccine was designed to induce one type of immune response, namely antibodies," says Jose Esposa, who is in charge of vaccine research at the United Nations agency UNAids.

"And some scientists believe that we may need vaccines that induce not only antibodies, but also another type of immune response that we call cell-mediated immunity."

Antibodies work on viruses outside human cells; with cell-mediated immunity, the immune system recognises cells which have already become infected and kills them.

We are managing to induce relatively high levels of immune responses in animals

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And Jose Esposa sees lots of new vaccine ideas coming from the modern sciences of genetics and genomics.

"There are now promising approaches; for instance, DNA immunisation or the use of other viruses that are genetically-engineered to carry HIV genes.

"With these tricks we are managing actually to induce relatively high levels of immune responses in animals, in monkeys - but also in initial trials in humans. So I am very optimistic now."

'Chemical condom'

As well as drugs and vaccines, scientists have another line of attack against HIV - microbicides.

These are a kind of chemical condom; the woman puts them in the vagina before sex, and they kill off the virus, protecting her from infection.

Costly treatments aren't available in the developing world

The problem is that so far, none of them have been shown to work. Researchers had high hopes of one called Non-Oxynol 9 or N-9 - but they were dashed recently when a major study found it damaged the lining of the vagina, increasing the chances of infection.

"In the laboratory it had very good anti-HIV activity," says Janet Darbyshire.

" But clearly when it was tested in the clinical trial there was a higher rate of infection in the women who took N-9 than in the placebo group.

"But several products are at quite late stages of development - going through safety trials and hopefully moving into phase three trials in the near future."

Natural defences

More basic science too continues to provide ideas for completely different types of Aids treatment.

A few years ago the Nobel laureate Philip Sharp made an astonishing discovery - that humans have a natural defence against viruses at the genetic level.

Now he's found a way to exploit this defence system using material called double-stranded RNA, using it to block genes which the virus needs.

"We can either switch off a cellular gene that's important for the virus to infect the cell, or we can switch off the viral gene during the infection," Doctor Sharp explains.

" I think this work demonstrates a sort of proof of concept; it takes a very long time to go from this early stage experiment to anything which can be effective."

We still have much to learn

Jose Esposa, head of vaccine research at UNAIDS

In the long term then, the prospects for effective HIV treatments look bright.

But Jose Esposa emphasises that HIV remains a potent enemy; scientists need to work, he says, with every idea they have.

"We have to be clear that although we know a lot about HIV, we still have much to learn. Sometimes people tell me that we already have all the scientific information we need to control the epidemic.

"The fact that there are fifteen thousand people becoming infected with HIV every day for me are the best proof that we don't have the ideal preventive or therapeutic tools and that we have to continue research to develop those tools that will allow us to control the epidemic in the future."

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