Warning Is Sent to AIDS Vaccine Volunteers
S. Africans Among Recipients Who May Be at Higher Risk of Contracting Virus
Thursday, October 25, 2007; Page A20
JOHANNESBURG, Oct. 24 -- South African AIDS researchers have begun warning hundreds of volunteers that a highly touted experimental vaccine they received in recent months might make them more, not less, likely to contract HIV in the midst of one of the world's most rampant epidemics.
The move stems from the discovery last month that an AIDS vaccine developed by Merck & Co. might have led to more infections than it averted among study subjects in the United States and other countries. Among those who received at least two doses of the vaccine, 19 contracted HIV compared with 11 of those given placebos.
Researchers shut down the trial on the grounds that the vaccine was proving ineffective, but the surge in infection among vaccinated volunteers prompted intense scientific debate and anxiety among researchers. The failure of the Merck vaccine is the latest in a series of disappointing results for research projects aimed at curbing AIDS.
"This is my worst nightmare," said Glenda Gray, the lead South Africa investigator for the vaccine study. "I haven't slept for days. I have a headache. I'm ready to resign from trials for the rest of my life."
Researchers in Soweto, Cape Town, Durban and two other sites began contacting South Africa's 801 trial participants on Tuesday, mainly by cellphone text message. The goal is to tell each one individually whether they had received a placebo or the vaccine, a process called "unblinding" the trial. Researchers are telling the roughly half who received the vaccine that it might have increased their risk of contracting HIV.
"It's quite shocking," said Nelly Nonoise, 26, who had received three injections of the vaccine in her left shoulder.
She added, "I probably wouldn't have joined the study knowing there's a risk."
Another participant, Nonhlanhla Nqakala, 22, said she thought the text message urging her to visit the vaccine test site meant she had tested positive for HIV. Her brother and a close friend had the disease and died, she said.
Nqakala said she was relieved when a doctor explained that she was not infected, but the news of a possible problem with the vaccine -- she had received three doses, not placebos -- left her distressed. "I thought the trial would help us find a cure for HIV," she said.
Merck developed the vaccine in conjunction with the U.S. National Institutes of Health , and until September's announcement, researchers worldwide considered it the most promising candidate yet in a multibillion-dollar quest for an AIDS vaccine dating to the 1980s.
Scientists crafted the vaccine by genetically altering a common virus to include elements of HIV. They hoped that it would trigger an immune response that would make recipients less likely to contract HIV, or at least delay the onset of full-blown AIDS.
The vaccine could not have caused infection, researchers say, but it could have caused immunological changes that made it easier for the virus to take hold during a later exposure.
The Merck vaccine trials took place in 15 cities in the United States, including Boston, Los Angeles and New York, and three in Canada. There also were sites in Peru, Brazil, Australia, Haiti, the Dominican Republic and Jamaica. Those trials began in December 2004 and included 3,000 participants, mostly gay men.
In South Africa -- where an estimated 5.5 million people are infected with HIV, more than in any other country -- the study used the same vaccine but was administered separately. The trial here started later, with the first injections this year, and had its own ethics oversight board. Most of the subjects were heterosexual.
The ethics oversight board in the United States, which monitored the trial everywhere but in South Africa, has not decided whether to tell participants if they received the placebo or the vaccine, said Mark Feinberg, vice president for medical affairs and policy for Merck.
Continuing research could be compromised, he said, if participants were told immediately whether they received the placebo or the vaccine. Vaccine researchers are scheduled to meet in Seattle on Nov. 7.
"Given the complexity of the issue, we feel the best conclusions will be reached when all the data are analyzed in their entirety," Feinberg said from Atlanta, where he was traveling.
He added that individual participants who want to know whether they received the vaccine will be told. Researchers also are counseling all study participants that the vaccine may have increased HIV risk for those who received it.
Other AIDS studies also have had unexpected results. Trials of two vaginal microbicide gels to prevent HIV led to more infections among those using the products instead of placebos. A massive study in Zimbabwe of the ability of HIV counseling and testing to prevent the spread of the epidemic found more infections among those with expanded access to testing.