Federal researchers shut down a clinical trial of an HIV vaccine involving about 2,500 subjects after it is found to be ineffective at preventing healthy subjects from contracting the virus.
In another major setback for efforts to develop an HIV vaccine, federal researchers have shut down a key clinical trial after an independent panel of safety experts determined that volunteers who got an experimental vaccine appeared to be slightly more likely to contract the human immunodeficiency virus than those who got a placebo.
Investigators involved in recruiting volunteers and running the trial at 21 sites across the country were ordered Tuesday morning to stop immunizing volunteers with the genetically engineered HVTN 505 vaccine and to inform the nearly 2,500 people who participated in the study whether they got the vaccine or the placebo. All of the volunteers were men or transgender people who have sex with men.
The announcement came Thursday from the National Institute of Allergy and Infectious Diseases, known as NIAID, which developed the HVTN 505 vaccine and launched the advanced clinical trial in 2009. The vaccine was designed to prime the immune system to mount a robust defense against all three subtypes of the HIV virus.
Although earlier trials that tested the vaccine on fewer people suggested it was able to produce an immune response to HIV and had a good safety record, the larger trial revealed a "non-statistically significant increase in HIV acquisition among volunteers in the investigational vaccine group compared to those in the placebo group," NIAID said in a statement.
The difference in infection risk between the vaccine group and the placebo group could have been a matter of chance. Even so, the data failed to indicate that the vaccine was having - or would ever achieve - its intended effects of reducing one's risk of infection with HIV, the virus that causes AIDS.
Also discouraging was the fact that the three-shot vaccine regimen did not help suppress the replication of HIV in people once they were infected, NIAID noted.
"This is quite a substantial disappointment," said Dr. Scott Hammer, a Columbia University virologist who is one of the trial's principal investigators. But, Hammer added, "we've learned from every clinical efficacy trial we've done. We've had good and bad news, but each one takes us a little closer in terms of what to pursue and not to pursue."
Altogether, there were 41 HIV infections among the 1,250 study volunteers who got the experimental vaccine and 30 infections among the 1,244 who received the placebo.
Of the 23 volunteers who became infected with HIV in the first 28 weeks of the study, 14 had received the vaccine and nine had received the placebo.
The experimental vaccine was also a disappointment for another reason: It failed to reduce the viral load of volunteers who became infected after they enrolled in the trial.
In its statement, NIAID said that it "remains committed to the pursuit of a highly effective, preventive HIV vaccine as part of a multifaceted HIV prevention research program." Meanwhile, it said that study volunteers who became infected during the trial would be referred to local services "for appropriate care and treatment." The study's investigators would continue to follow those volunteers for five years from the time they enrolled, NIAID said.
This is not the first large HIV vaccine trial to end abruptly after initial results proved disappointing. In 2003, early trials testing a Genentech Inc. vaccine known as Aidsvax found that some who got it developed HIV - prompting government regulators to block further testing in the United States. In 2007, a trial in South Africa that tested a vaccine made by Merck & Co. was ended prematurely because participants who got the active vaccine were found to have higher rates of infection than those who did not.
The HVTN 505 vaccine regimen was an outgrowth of one of those disappointments. Researchers improved upon the Aidsvax vaccine and tested the new formulation, called RV-144, in heterosexuals in Thailand. In 2009, they found that it reduced infection rates by 30%.
The HVTN 505 vaccine incorporated many of the lessons learned from the RV-144 trial about constructing a vaccine that would train the immune system to recognize and fight the genetic guts of the virus as well as its "envelope," or outer cell wall.
That those lessons failed to yield a successful vaccine in the NIAID trial was a bitter disappointment to researchers. In the coming weeks and months, researchers will be poring over two years' worth of blood samples from volunteers, said Dr. Stephen J. Brown, medical director of the AIDS Research Alliance, the Los Angeles site participating in the HVTN 505 trial.
As they do so, Brown said, researchers are likely to glean new insights into which parts of the current vaccine might form the basis for new HIV-prevention regimens. The next HIV vaccine trials are to start next year in southern Africa.
The World Health Organization estimates that 34 million people worldwide are living with HIV, including 2.5 million who became infected in 2011 - a statistic that underscores the need for a vaccine. More than 25 million people have died since the HIV/AIDS epidemic began, according to the WHO.