Advance on AIDS Raises Questions as Well as Joy

Advance on AIDS Raises Questions as Well as Joy
By DONALD G. McNEIL Jr.
Copyright by The New York Times
Published: July 26, 2010
http://www.nytimes.com/2010/07/27/health/27aids.html?hpw


VIENNA — The best AIDS-prevention news in years was released here last week at a world conference on the disease: a vaginal gel, called a microbicide, that can be used without a man knowing it, gave women a 39 percent chance of avoiding infection with the deadly virus.

After more than a dozen microbicide failures, it was a huge relief, and led to cheering and standing ovations for the researchers here.

“This is a field that’s known a lot of pain,” said Catherine Hankins, chief scientific adviser for Unaids, the United Nations’ AIDS-fighting agency.

There was general relief that the data was not as shaky as that of an AIDS vaccine trial released in September.

“There’s a certain feeling of ease and pleasure for me as a scientist that any way you slice the data, it’s statistically significant,” said Dr. Anthony S. Fauci, a top AIDS expert in the United States government, which paid most of the trial’s costs.

There was an unexpected bonus: the gel protected women even better against genital herpes. (The investigators were not sure why, but it contained tenofovir, an antiviral drug, and AIDS and herpes are both viral.)

Now experts are pondering the many questions raised by the news.

How much more testing will it need to win approval from drug regulators?

Would more than 1 percent tenofovir in the gel, or a two-drug mix, work better?

Can it be made cheaply enough for poor countries? (The gel costs 2 cents a dose, but the applicators are 40 cents because they are patented and were frequently redesigned to be more comfortable.)

The women had sex an average of five times a month, and were instructed to insert gel before and afterward. Would one dose, which would be easier and cheaper, work just as well?

Will it protect prostitutes, who have sex with many men in succession? Is it safe enough to use daily?

Can pregnant women use it? (Some women got pregnant and gave birth, but were taken off the gel quickly to reduce any risk.)

Would women who use it but got infected anyway develop hard-to-cure drug-resistant infections?

And, although it was tested on poor African women, might it appeal to Western women, some of whom might worry more about herpes than AIDS?

Might it also work for anal sex, and protect gay men?

The investigators and other experts said they had only partial hints of answers, but most were encouraging.

And, given that this is AIDS research, which inevitably creates controversy, some hard questions were raised.

If it was known after the first year that the gel was working, why wasn’t the trial stopped?

And what will happen to the 889 African women who, in the words of Mark Harrington, an AIDS activist, “put their bodies on the line for this study”? Would they be able to keep getting the product that might have saved their lives?

Some questions were easy, said Dr. Salim Abdool Karim, a study leader and professor of epidemiology at both the University of KwaZulu-Natal in South Africa and Columbia University.

The price of a dose could fall below that of a condom because the applicators are just molded plastic and, without patents restrictions, “the Chinese could make them for half a penny,” he said.

Others, like what drug and dose combinations are best and safest, must be tackled in future trials. A complex multination trial of several methods, including microbicide, is due to end in 2013, but a rapid new one may be designed as quickly as possible.

Globally, more than a million women a year die of AIDS, so speed is important.

The gel has never been tested in men, but has protected monkeys given anal doses of the simian version of the virus. Dr. Karim said samples he took found that tenofovir in the women’s vaginal linings had migrated to their rectal linings too, meaning they might also have been protected against anal sex.

“The tissue between the two is very thin,” he said.

Using a gel rather than a pill meant the drug infused the genital tracts but hardly reached the blood. That lowered the chances that a woman who got infected anyway would develop tenofovir-resistant virus, experts said.

No woman developed it, but they were tested so often that the virus would have had little time to mutate.

Dr. Kevin A. Fenton, director of the AIDS division of the Centers for Disease Control and Prevention, said the one-two AIDS-and-herpes punch “could make it more attractive to American women.”

It’s not clear whether men would like gels, and tenofovir pills are being tested in uninfected gay men, but the results “are a real shot in the arm to the field,” he said.

The trial was not stopped early, Dr. Karim said, because the independent review board that could have done so wanted results so overwhelming that they would have equaled the results of two generally favorable trials, “and we didn’t achieve that level of efficacy.”

Dr. Sheena McCormack, a British microbicide researcher, recalled penicillin tests of 70 years ago. Those researchers gave it to their sickest patients, not a random sample, and it still worked astonishingly well. This, she said, more resembled trials of circumcision as an AIDS preventive, which took three to be convincing.

What happens to the 889 women is unclear. Dr. Quarraisha Abdool Karim, Dr. Karim’s wife and research partner, said more gel needed to be made and she hoped to enroll them quickly in a new trial so they could get it.

Mr. Harrington said he thought they ought to have a choice of being in another trial or just getting the gel indefinitely, even though it is not legally approved by any drug-regulatory agency yet.