Nevirapine Misinformation: Will It Kill?

by John S. James

December 23, 2004: For a few days last week an Associated Press

"exclusive" story touched off a firestorm of media by charging that

side effects of single-dose nevirapine (to prevent mothers with HIV

from infecting their babies during childbirth) had been covered up.

Later the AP quoted responses -- one comparing nevirapine's

distribution in Africa to the notorious Tuskegee Experiment, another

charging that Africans were treated like guinea pigs. In fact there

never was any evidence of a significant risk of side effects from only

a single dose of nevirapine. There is a risk of HIV drug resistance

from using even a single dose of the drug alone, but this is well known

to all AIDS doctors and experts and has never been covered up.

Every day about 1,800 babies are born with HIV, mostly to women who

have no treatment options either for themselves or to prevent the

infection of their child. There is no reason to doubt that single-dose

nevirapine works, and could prevent about half of these infections.

The brief media storm that still threatens the lives of thousands of

unborn children grew out of a bitter dispute between two officials of

the U.S. National Institutes of Health -- one of whom selectively

released "thousands" of documents (according to news reports) to

reporters and/or members of Congress. The danger now is that misleading

stories published around the world will cause patients, doctors, or

even some governments to reject single-dose nevirapine to prevent

mother-to-child HIV transmission, even when no other treatment choice

is possible.

Background

Nevirapine was approved in the U.S. in June 1996, for use in

combination with other antiretrovirals for treating HIV. For this use

it is taken twice a day for as long as the virus is under control.

Later, a study in Uganda from 1997 to 1999 (the HIVNET 012 clinical

trial) found that a single dose of nevirapine given to the mother and a

single dose to the infant reduced HIV transmission to about half of

what it was with a very short course of AZT. This study, conducted as a

collaboration between researchers from Johns Hopkins University and

Uganda and funded by the U.S. National Institutes of Health (NIH), was

published in September 1999. It showed that HIV transmission at

childbirth could be greatly reduced by a very inexpensive and easy

regimen, even when the mother had little or no prenatal care. It is

rightly considered one of the great successes in HIV prevention.

Nevirapine alone is not the best regimen, however. Later it was learned

from the same study that even the single dose sometimes selects for

resistance mutations in the mother's HIV -- a serious problem because

it could make her treatment more difficult in the future. This can be

prevented by treating the mother's HIV if she needs antiretroviral

treatment, which of course should be done anyway -- or by using a much

more difficult regimen of AZT to prevent transmission -- or by adding

other drugs (usually AZT plus 3TC) to suppress the virus while the

nevirapine is slowly eliminated from the body. But still today the

great majority of women with HIV do not have access to any

antiretroviral treatment. Single-dose nevirapine is inexpensive and

easy to deliver -- and many women will not use a longer course of

medication, because they are afraid of the consequences if people

around them learn or suspect that they have HIV.

The recent controversy developed because after the Uganda study had

been published, an NIH audit found that data on possible side effects

had not been reported correctly by the Ugandan staff. This problem in

one trial did not change the known safety of single-dose nevirapine --

which has been tested in many other clinical trials and widely used to

prevent maternal transmission, without side effects. In continuous,

long-term use in HIV treatment, serious or fatal side effects can

occur, as with any antiretroviral. But these are rare, and they can be

prevented with proper medical care, and they do not happen with one

dose. Aside from the HIV resistance problem, there is no evidence of

any significant safety risk from a single dose of nevirapine.

The current dispute arose after NIAID/NIH hired a physician with

clinical-trials monitoring experience, Jonathan M. Fishbein, M.D., in

July, 2003, to help it correct the kinds of deficiencies that had been

found in the study conducted several years earlier in Uganda. The key

issue seems to be whether the reporting problems found in that study

should invalidate the conclusion that single-dose nevirapine is safe

and effective for preventing maternal-infant transmission. Recently Dr.

Fishbein, still a Federal employee, claimed whistleblower status and

used his Web site, http://www.honestdoctor.org, to release selected

documents about problems with the nevirapine study.

Comment

We looked through all the documents on Honestdoctor.org as of December

22, 2004, and found nothing there that raised any new doubt on

single-dose nevirapine -- now established by much more than the one

trial in Uganda. Instead, the documents on that site show the extensive

work that NIH and others were doing, both before and after Dr. Fishbein

was hired, to correct universally acknowledged technical reporting

problems. The goal was and is to re-analyze the Uganda trial in the

light of all available information, both to re-check the conclusions,

and also to improve clinical research in the future, particularly in

developing countries, which often have a steep learning curve in

applying standards created for pharmaceutical-company research in the

West. I have no idea why Dr. Fishbein alleged "widespread scientific

and professional misconduct at the NIH Division of AIDS (DAIDS)" (quote

from Honestdoctor.org).

There is no reason to doubt that single-dose nevirapine works and

reduces HIV transmission to about half of what it would be without

treatment. (It may do better than that, since the comparison group was

not a placebo but a very short course of AZT, which may have had fewer

HIV transmissions than a placebo would have.) The NIH Division of AIDS,

like almost all other experts, wants to focus on public-health efforts

to make preventive and other treatment available, and not derail these

efforts because of technical problems in a trial that ended five years

ago. This is not "scientific and professional misconduct."

AIDS organizations did well last week in answering the misinformation

about nevirapine. But the damage had already been done. The story went

out on December 13, and was totally unexpected because it was tied to

no medical or scientific development; it went around the world

immediately and no answer could catch up. It is possible that children

have already been born with HIV as a result, and that many more will be

infected unnecessarily.

What Can We Learn for the Future?

This is not the last time the AIDS world will face mass-media storms

that carry serious misinformation throughout the world. What can we do

about it?

AIDS needs a major organization dedicated to consensus development, and

able to offer reporters a single entry point to learn what credible

consensus exists on almost any AIDS issue. No position will speak for

everybody, but the process should be open to hearing and understanding

all dissenting views. Two or more incompatible consensus clusters could

emerge, and they would have to be represented by different

organizations. But reporters could immediately find broadly credible

consensus statements, and talk with experts who have worked on an issue

for years. They may still publish misinformation, but at least an

answer could go out with it -- or be clearly missing from their story.

Years ago AIDS had well-known broad policy organizations, like the AIDS

Action Council in Washington DC. But they represented insiders with

their own interests more than a national or world community. For

example, treatment, research, and international issues were mostly

locked out for years -- and usually the only way to have a voice was to

be part of the scene in Washington. Still these organizations served an

important purpose in providing a common policy base for reporters and

others, and we miss that today.

But now we need a new kind of organization that prides itself on

listening and learning from different people (almost like social

scientists exploring what is out there instead of imposing their own

view) -- but then finds and suggests practical, creative ways these

views and movements can work together in a larger whole.

__________________________________________

Communication Note

Ten days into this controversy Dr. Fishbein has a better Web site than

most AIDS organizations do after many years -- immediately raising the

communication standard. AIDS will face new media storms in the future,

and must get its house in order.

Honestdoctor.org is very well organized, allowing readers to see

immediately what is available and navigate to what they want. The site

has a extensive collection of the recent press articles, consistently

and attractively laid out. Under "Definitions" it has a list of

acronyms and a list of people with their titles -- and will have a

glossary and organizational diagrams. When documents are photographed

and displayed as images, they are processed correctly, so that they are

entirely readable and yet download rapidly on any Internet connection.

And last but not least this site has clearly legible type on its main

pages, when most sites have text that is too small, too light, or

without enough contrast between text and background.

In the future, AIDS organizations should ask for volunteer or

professional Web help that can do at least as well. Remember that our

visitors have millions of other pages a few clicks away, and if a site

is hard to read or hard to use, many will leave.

____________________________________________

For More Information

Here are sources for more information on the recent nevirapine

controversy. Except for the last one, they are December 2004 statements

or articles in chronological order.

* December 14, 2004, "Elizabeth Glaser Pediatric AIDS Foundation on

issue of prevention of mother-to-child transmission of HIV/AIDS and

single-dose nevirapine,"

http://www.pedaids.org/press_release_nevirapine_december_14_2004.htm

* December 15, "Project Inform statement regarding the use of

single-dose nevirapine to prevent mother-to-child transmission of HIV,"

http://www.projectinform.org/news/04_12nvppr.html

* December 15, Treatment Action Campaign, South Africa, "Single-dose

nevirapine is safe and effective: But public health facilities must

switch to more effective regimens wherever possible."

http://www.tac.org.za/newsletter/2004/ns15_12_2004a.html

* December 17, the U.S. National Institute of Allergy and Infectious

Diseases, "Questions and answers: The HIVNET 012 study and the safety

and effectiveness of nevirapine in preventing mother-to-infant

transmission of HIV,"

http://www2.niaid.nih.gov/newsroom/Releases/HIVNET012QA.htm

* December 21 The New York Times, "Furor in Africa Over Drug for Women

with HIV,"

http://www.nytimes.com/2004/12/21/international/africa/21aids.html

* December 22, Nature, "Activists and Researchers Rally Behind AIDS

Drug for Mothers,"Nature.December 23, 2004; volume 432, page 935.

* December 25, Science, "Allegations Raise Fears of Backlash Against

AIDS Prevention Strategy,"Science. December 25, 2004; volume 306, pages

2168-2169.

* You can find more background on nevirapine for prevention of mother

to child transmission at

http://womenchildrenhiv.org/

--

John S James

AIDS Treatment News

www.aidsnews.org