By Michael Day

New Scientist

16 Dec. 2000

Four years of "hit hard, hit early" HIV treatment may be on the way out in the US, as evidence mounts of the drugs' serious side effects

AIDS experts in the US are about to complete a humiliating U-turn when the Department of Health and Human Services launches its revised HIV treatment guidelines in January.

The revisions will underline the need to hold back from using powerful antiviral drugs until the immune systems of HIV patients show significant signs of decline. It reflects the view, long held by British doctors, that early use of currently available drugs may do more harm than good.

Charles Carpenter, associate director of the Brown University AIDS programme, told a Royal Society of Medicine meeting in London last week: "In retrospect, we now realise the risk of drug toxicity is greatly enhanced by taking these drugs early."

For the past four years, leading American physicians have led the "hit hard, hit early" campaign which encouraged patients to take cocktails of powerful antiviral drugs in the early stages of the disease in the hope of preventing damage to the immune system.

British doctors were often ridiculed at conferences and in the pages of research journals for suggesting the drugs be used more cautiously, in case they proved too toxic for patients who take them for years or decades at a time.

Carpenter is in charge of producing the US version of the International AIDS Society treatment guidelines. They have just fallen into line with British HIV Association guidelines which recommend that patients should not get triple therapy until their "CD4 count"--the number of T-helper immune cells--falls to less that 350 per millilitre of blood. The normal level is around 800 per millilitre.

"This shows that for us all medicine is a very humbling process,"Carpenter told the audience of US and British AIDS experts.

"It's wonderful to see how after a long period you've moved closer to us," replied Ian Weller, head of clinical HIV research at University College London. "The hit hard and early crowd are now hitting hard but later."

Weller, who is also deputy chairman of the Medical Research Council's HIV Therapeutics Trials Committee, has long voiced fears that taking a combination of protease inhibitor and transcriptase inhibitor drugs early on in HIV disease could do patients more harm than good.

In January, the other major source of guidance for American doctors treating people with HIV, the DHHS/National Institutes for Health, will publish their own revised guidelines. New Scientist has learned these will also adopt the more cautious approach favoured by British experts.

Anthony Fauci, head of the NIH's AIDS research division programme, has publicly stated that doctors have underestimated how difficult it is to stick to the treatments.

Anti-HIV drugs have been linked to a disfiguring redistribution of body fat, liver disease and damage to mitochondria, as well as less specific ailments such as nausea and tiredness. The drugs also have to be taken in complex combinations every day.

"It does reduce the quality of life for several years," said Carpenter. But both doctors noted that the drugs have been successful in extending the lives of people with AIDS.

Nonetheless, Weller added that the start of treatment might have to be delayed even further, as new side effects emerge. He noted that the vast majority of serious AIDS-related infections occurred in people with CD4 counts less than 200.

The speakers agreed that early treatment might be justified in people who had only just become infected. In such people, there was still the possibility of protecting a special class of T cells that are destroyed very early in infection.