Made in India. The Ideal `Cocktail' for AIDS

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Made in India, the Ideal `Cocktail' for AIDS

By DONALD G. McNEIL Jr. New Yourk Times. Published: May 4, 2004

A three-year study of AIDS drugs has identified what the research

leaders believe is the ideal triple-therapy cocktail for new patients.

The successful cocktail, known colloquially as " two nukes plus a non-

nuke, " is the same one that the World Health Organization has been

recommending in poor countries since 2002. It is also the same

combination that Indian suppliers of generic drugs have been putting

in three-in-one pills since 2001.

Another drug cocktail examined in the study — a " three-nuke

combination " — did so poorly that patients were taken off it. The

failed cocktail is the only one made as a three-in-one pill by any

Western pharmaceutical company.

The study, its authors said, suggests that patients who have never

been on AIDS drugs should be started on a combination of two

nucleoside reverse transcriptase inhibitors ( " nukes " ) and a non-

nucleoside reverse transcriptase inhibitor ( " non-nuke " ).

Currently, American and European doctors prescribe many different

mixes of the 20 drugs approved for fighting AIDS infections, and

shift the mixes as patients develop resistance or side effects.

The study of 1,147 patients, published in the April 29 issue of the

New England Journal of Medicine, looked for an ideal regimen for new

patients that avoided protease inhibitors. Those drugs are effective

and often prescribed by Western doctors, but they can damage the

liver or shift body fat into unsightly humps.

The study was begun before any drugs in the two newest classes of

AIDS drugs, fusion inhibitors and integrase inhibitors, were approved.

AIDS experts said a second conclusion from the study was that the

three-in-one pills offered by generic drug makers from India were

better for new patients than any of those sold or planned by Western

drug companies.

The study " reinforces the point " that the type of cocktail

recommended for poor countries by the World Health Organization is

right for rich countries as well, said the study's lead author, Dr.

Roy M. Gulick, director of the H.I.V. clinical trials unit at Weill

Cornell Medical College in New York City.

The latest guidelines from the National Institutes of Health for

American doctors recommend starting new patients either on the same

two-nukes-plus-a-non-nuke regimen that the W.H.O. recommends, or a

two-nukes-plus-a-protease-inhibitor regimen.

Most of the Weill Cornell study's 1,147 patients were nonwhite and 19

percent were women, Dr. Gulick said, so the study's conclusions

should be applicable worldwide.

The AIDS expert who led the committee that formulated the W.H.O.

guidelines, Dr. Hammer, chief of the division of infectious

diseases at Columbia Presbyterian Medical Center, said the W.H.O.

made its 2002 recommendation because the combination worked well and

the drugs were generally cheap.

Besides their toxicity problems, he said, protease inhibitors were

expensive because only companies that held patents on the drugs made

them, and some of the medications required refrigeration, which is

impossible to guarantee in, for example, rural Africa.

In the new study, the cocktail that worked best was a mix of

the " nukes, " AZT and lamivudine plus the " non-nuke " efavirenz. After

32 weeks on the cocktail, 89 percent of the patients had almost

undetectable levels of virus in their blood.

The cocktail that did less well was a mixture of AZT and lamivudine

plus abacavir. After 32 weeks, only 79 percent of the patients had

low levels of virus.

That cocktail is sold by GlaxoKline as a three-in-one pill under

the name Trizivir.

However, because it is " clearly inferior " at suppressing the virus,

it is " no longer recommended for first-line use " said Dr.

Bangsberg, a professor of medicine at the University of California at

San Francisco who monitors treatment around the world.

Most of the study was paid for and monitored by the National

Institute of Allergy and Infectious Diseases, part of the National

Institutes of Health.

Glaxo provided its drugs and paid part of the analysis costs, said

Faye Dark, a Glaxo spokeswoman.

" We aren't surprised that Trizivir alone didn't do as well, " Ms. Dark

said. The decision to take the study's patients off it was made in

February 2003.

But she said the cocktail still worked in many patients and should

play a role in AIDS therapy, especially for maintaining patients

whose viral loads have first been lowered by other regimens.

Most three-in-one pills now made by Indian generics makers contain

AZT, lamivudine and nevirapine.

Nevirapine is in the same " non-nuke " class as efavirenz and a recent

study in Lancet, the British medical journal, found them to be

equivalent. Nevirapine is a well-established drug, but it causes a

serious rash in some patients, so generics makers are moving toward

making compounds with efavirenz as well.

The N.I.H. guidelines prefer efavirenz because it causes fewer

rashes, but accept nevirapine as a substitute.

Both the " nukes " and " non-nukes " block reverse transcriptase, an

enzyme that allows the RNA in an AIDS virus particle to replicate

itself inside the DNA of a healthy T cell, a trigger cell for the

body's immune system. Unable to replicate, the virus cannot spread to

other T cells and destroy the immune system.

http://www.nytimes.com/2004/05/04/health/policy/04AIDS.html?

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