Tenth of H.I.V. Cases in a Study in Europe Are Resistant to Drugs

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http://www.nytimes.com/2003/07/16/health/16DRUG.html?th

 

July 16, 2003Tenth of H.I.V. Cases in a Study in Europe Are Resistant to DrugsBy

DONALD G. McNEIL Jr.

 

 

he biggest study, so far, of resistance to AIDS drugs, to be released today at

an international AIDS conference in Paris, finds that about 10 percent of all

newly infected patients in Europe are infected with drug-resistant strains.

 

The researcher who led the study called the level of resistance to some

anti-AIDS drugs " surprisingly high. " Other scientists at the conference agreed

that the findings had worldwide public health implications and made the hunt for

new classes of AIDS drugs even more critical.

 

They said the figure suggested that many AIDS patients who are in treatment go

back to engaging in high-risk sex or needle-sharing. It also suggested that an

" order of battle " approach to prescribing AIDS drugs, like that used for

tuberculosis medicines, should be adopted in place of the current free-for-all.

 

For example, one researcher said, a drug like nevirapine, which can prevent

mother-child transmission with just one dose, might be restricted to that use

only, so resistance to it cannot grow as it would if thousands of patients were

put on it for life. Also, public health authorities could tell doctors which

drug combinations to prescribe first, second and third as resistance was

encountered.

 

Smaller tests to measure resistance have been done in San Francisco, in a group

of nine other American cities and in Switzerland. While some of those studies

found higher levels of resistance — of 225 patients in San Francisco, 27 percent

were drug resistant — the new study is thought to be the first to give a

reliable measure of the phenomenon across a broader population, said Dr. Charles

Boucher, the virology professor at Utrecht University who led the new study.

 

" You're not talking about high-risk inner city San Francisco, " he said. " This is

across Europe. "

 

Some doctors said the study suggested that all new AIDS patients should be

tested to determine the drug resistance of the strains infecting them.

 

Those tests can cost between $200 and $800 each and take between a week and a

month to complete, factors that could greatly raise the price of plans to bring

inexpensive AIDS drugs to poor countries. For example, the Bush administration

has promised to spend $15 billion bringing such drugs to Africa and the

Caribbean.

 

But experts emphasized that the possibility of creating drug-resistant strains

of the virus that causes AIDS was not a reason to deny drugs to the poor.

 

Dr. Robert M. Grant, a professor of medicine at the University of California at

San Francisco, who led the San Francisco study, said that doing so would be

unethical. Dr. Boucher said it would also be medically unwise, since the drugs

drive down virus levels, making transmission less likely.

 

Other experts said that the findings underscored the need for better guidelines

on the medicines' use as the treatment effort gears up. " It means we have to be

smart about how we use the drugs to avoid as much resistance as we can, " said

Dr. Scott M. Hammer, chief of infectious disease at Columbia-Presbyterian

Medical Center in New York, who attended the International AIDS Society

conference in Paris this week and saw an early copy of the study.

 

The study tested 1,633 patients from 17 European countries who had just been

diagnosed with the virus that causes AIDS and who had not yet been treated for

it. (It is nicknamed the Catch study for " combined analysis of resistance

transmission over time of chronically and acute infected H.I.V. patients in

Europe. " )

 

About 9.6 percent of the patients were resistant to at least one of the three

types of anti-retroviral drugs that suppress the virus that causes AIDS.

 

There are 17 such drugs, but they fall into three classes: nucleoside

reverse-transcriptase inhibitors, non-nucleoside reverse-transcriptase

inhibitors and protease inhibitors. Normally, a patient takes a " triple therapy

cocktail " of all three to attack the virus at three different sites.

 

Resistance to the first group was found in 6.9 percent of those studied,

resistance to the second in 2.6 percent and resistance to protease inhibitors in

2.2 percent.

 

Two new classes of drugs, fusion inhibitors and integrase inhibitors, are still

in testing stages, so resistance to them is presumed not to exist yet.

 

Drug-resistant strains appear because the virus mutates rapidly and they thrive

when patients take their drugs carelessly. For patients to be newly infected

with resistant strains, they must have been infected by people with H.I.V. who

had gone back to high-risk behavior despite having caught a disease that is

usually fatal.

 

No large study of drug resistance has been done in Africa. It is too early, Dr.

Boucher said, because so few Africans are getting treatment.

 

In sub-Saharan Africa, where 2.4 million people died of AIDS in 2002, only about

50,000 are getting anti-retroviral drugs, according to the United Nations.

 

For that reason, argued Dr. Roy M. Gulick, a professor at Cornell University's

Weill Medical College, there is probably little point in doing expensive tests

for resistance in Africa now.

 

" The risk of resistance in most African populations right now is very low or

zero, " he said.

 

That likelihood was borne out by another result in the Catch study. Resistance

was much higher, at 11.3 percent, among Europeans who had subtype B of the virus

that causes AIDS, compared to those with non-B subtypes, in whom it was 3.3

percent.

 

Subtype B infects 98 percent of Americans and about 60 percent of Europeans. It

is the subtype that has spread most widely since AIDS was discovered in Los

Angeles, San Francisco and New York in the early 1980's. Though subtype B

originally came from central Africa, subtypes A, C and so on prevail in other

parts of Africa and in Asia. Researchers believe Europe has a broader mix than

the United States because more Africans and Asians immigrate there from former

colonies.

 

But the growth of resistance " is a fact of life, " said Dr. Joep Lange, a

professor of internal medicine at the University of Amsterdam and president of

the International AIDS Society. " It happens with antibiotics; it happens with

TB. If you use drugs, you'll eventually see resistant strains. "

 

Therefore, he and other researchers said, when the drugs come to Africa, they

must be handed out carefully, with laboratories, doctors and epidemiologists

monitoring patients and community resistance.

 

Dr. Gulick said the study also showed that prevention efforts in wealthy

countries needed to be focused not just on uninfected young people, but on

infected ones, " to tell them, `You have the infection but you shouldn't spread

it to other people,' " he said.

 

Copyright 2003 The New York Times Company

 

 

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