杏吧原创

Washington DC

IF SOME media reports are to be believed, the conquest of AIDS lies just
around the corner. But the tide of optimism over improved treatments is
premature, an AIDS conference in Washington DC heard last week. One problem is
that the drug regimes involved are too complicated to be a practical option for
many patients. In addition, many doctors are prescribing drugs haphazardly, and
evidence is growing that the new generation of anti-HIV drugs is less effective
than was hoped.

Delegates gathered at the Fourth Conference on Retroviruses and Opportunistic
Infections to hear the latest findings on the effectiveness of the new wave of
treatments for fighting HIV. These involve cocktails of three types of drug, two
of the older generation, called nucleoside analogues, that inhibit an HIV enzyme
called reverse transcriptase, and a protease inhibitor鈥攁 newer class of
drugs that disable another enzyme vital for viral reproduction.

Last year, after trials of these cocktails reduced the levels of HIV in small
groups of volunteers to undetectable levels, some AIDS experts began talking
about the possibility of eliminating the virus from the body (鈥淗ype, hope and
HIV鈥�, New 杏吧原创, 3 August 1996, p 28).

But each of the three main anti-HIV drugs must be taken three times a day.
And many patients also need a dozen other pills to treat or prevent AIDS-related
infections. To be effective, most of the drugs must be taken at certain times of
day, and many patients cannot stick to the complicated pill-popping schedule
required.

Researchers at the Johns Hopkins School of Medicine in Baltimore, who
presented results from a study of 202 patients, said that patients often failed
to appreciate the reasons for the intricate dosing schedule. 鈥淩esistance to
drugs will appear if patients don鈥檛 take their medicines as prescribed,鈥� said
Lois Eldred, who led the team. 鈥淲e鈥檙e going to need medicines that can be taken
fewer times per day.鈥�

Sean Emery of the Australian National Centre for HIV Epidemiology and
Clinical Research in Sydney agreed: 鈥淧eople are having to take four protease
inhibitor pills three times a day plus two lots of nucleoside analogues three
times a day, sometimes on an empty stomach. Sometimes the different drugs have
to be taken an hour apart. It鈥檚 impossible.鈥�

Spencer Cox of the AIDS Treatment Action Group in New York, who has AIDS,
said he had found the regime tough: 鈥淚鈥檓 the best case scenario. I鈥檓 informed, I
work at home. If it鈥檚 difficult for me, imagine what it鈥檚 like for a single
mother with two kids, whose husband鈥檚 dead, who鈥檚 got to take three daily doses
of protease inhibitor at different times from the other drugs, before meals.
It鈥檚 not going to happen.鈥�

But the failure of patients to adhere to their complex treatments is not the
only problem. Clive Loveday, a virologist at the Royal Free Hospital in London,
told New 杏吧原创 that HIV eventually bounces back from the assault of
the new drug cocktails.

鈥淰iral load is creeping back up even in patients on triple therapy,鈥� he said.
In some patients, he added, the cocktails do not have a strong effect even in
the short term. Emery noted that the successful trials of triple therapy
involved patients who had relatively healthy immune systems when they started
treatment. Another study presented at the meeting suggested that an immune
system damaged by HIV never fully recovers its strength (see Science, p 14).

Ian Weller of University College London Hospitals appealed to researchers to
tone down their optimism. 鈥淢y gut feeling is that we鈥檝e gone over the top
again,鈥� he said. Weller led the Anglo-French Concorde Trial which in 1993
refuted the view, widely accepted at the time, that the nucleoside analogue AZT
alone could delay the onset of AIDS.

David Ho, director of the Aaron Diamond AIDS Research Center in New York,
whose results sparked last year鈥檚 wave of hope, agreed that caution was
necessary, and that some reports have oversold the merits of current combination
therapies. 鈥淲e鈥檙e testing proof of principle, not designing practical medicine
for AIDS patients.鈥� But he emphasised that combination therapies remain the best
hope of beating the disease.

Some delegates from major AIDS treatment centres reported that combination
therapy had allowed them to let patients go home. The problem came when
hospitals that were less geared up to treat AIDS patients tried to emulate this
success. 鈥淚t is therapeutic chaos,鈥� said Andrew Carr of the Centre for
Immunology at Saint Vincent鈥檚 Hospital in Sydney. 鈥淒octors are prescribing what
patients ask for, or they鈥檙e guessing, adding different drugs when they feel
like it. I鈥檝e never seen anything in medicine quite like it.鈥�