Federal health officials announced today (April 25) that they had stopped an experimental HIV vaccine trial, known as the HVTN 505 Study, due to evidence it did not protect against transmission of the virus nor reduce viral loads in those who became HIV positive.
It was another setback in AIDS researchers’ long-held hope of discovering a vaccine that can block HIV transmission. Another vaccine trial known as the Step Study came to an abrupt end in 2007 for similar reasons, as well as because it was found that trials’ vaccine increased some uncircumcised male participants’ risk of acquiring HIV.
The National Institutes of Health disclosed its decision to halt the HVTN 505 Study in a statement released to the press. It also revealed that during the first two years of the study 41 volunteers who had received the investigational vaccine regimen acquired HIV as did 30 volunteers given a placebo vaccine.
The study began enrolling 2,504 men who have sex with men and transgender people who sleep with men in 2009 in 19 cities across the country. As a Bay Area Reporter article noted then, San Francisco researchers had planned to enroll 120 Bay Area men into the study.
But due to positive results from a Thailand-based trial of the vaccine in heterosexual people, the size of the U.S. trial was increased. In San Francisco 215 people, most MSM but also a small sample of transgender women, took part.
Dr. Susan Buchbinder, director of the Bridge HIV research section of the San Francisco Department of Public Health, posted a statement online expressing that she was “disappointed” about the discontinuation of the trial study.
“We, at Bridge HIV, want to thank all of the participants who enrolled at our site, and around the United States, for their commitment to finding an effective HIV vaccine,” wrote Buchbinder. “Their dedication will bring us one step closer to having a safe and effective global vaccine for the future.”
In a phone interview with the B.A.R., Buchbinder said it is unclear why the vaccine showed different results between the Thai and American participants.
“The good news is we are developing vaccines similar to, and perhaps a little bit better than, the Thai vaccine for testing in South Africa in heterosexuals and hopefully in North and South America in MSM,” she said. “We are already doing earlier phase studies on those vaccines.”
The HVTN 505 Study involved a prime-boost vaccine regimen developed by the Vaccine Research Center housed within the National Institute of Allergy and Infectious Diseases. Participants were given a series of three immunizations over the course of eight weeks, beginning with a DNA-based vaccine designed to prime the immune system.
The vaccine was created to mimic the genetic material of the HIV virus but did not contain any live or killed HIV and could not transmit HIV to those who were vaccinated.
Participants given the vaccine received a single injection at week 24 with a recombinant vaccine (the booster vaccine) based on a weakened adenovirus type 5 (Ad 5), a common cold virus. The Ad5 virus used in the study’s vaccine regimen was disabled so that it could not cause a cold or other respiratory illness.
Problems with the vaccine were discovered Monday, April 22 during a review conducted by the study’s independent data and safety monitoring board. The panel had met to examine data from the 1,250 volunteers who received the investigational vaccine regimen and the 1,244 volunteers who received the placebo vaccine.
The primary analysis looked at volunteers who were diagnosed with HIV infection after having been in the study a minimum of 28 weeks, according to the NIH statement. It showed that 27 HIV infections occurred among vaccine recipients and 21 occurred in the placebo group.
Among volunteers who became HIV-infected before the 28 week mark of the study, 14 cases of HIV infection occurred among those who received the investigational vaccine regimen, and 9 HIV infections occurred among the placebo vaccine recipients, reported the NIH.
Additionally, the monitoring board found that the vaccine failed to reduce viral load among volunteers who acquired HIV infection at least 28 weeks after entering the study and who had been followed for at least 20 weeks after diagnosis. There were 30 participants with measurable viral load (15 vaccine recipients; 15 placebo recipients), reported the NIH.
Based on its findings of the review, the monitoring panel recommended that no further vaccinations with the investigational vaccine regimen be administered. The NIAID concurred and instructed all of the HVTN 505 Study sites to immediately cease administering injections.
The trail sites will continue to follow-up with study participants so the researchers can further evaluate the trial data.
One issue they will be investigating is why there was a “non-statistically significant increase” in HIV acquisition among the vaccine group volunteers compared to those in the placebo group. NIH officials reported that they do not fully understand why there was such an increase and need to conduct further analysis before drawing “any firm conclusions.”
In her online statement Buchbinder noted that despite the cancellation of the trial, the federal officials “commended the staff on a very well-conducted study that will allow us to learn a tremendous amount, even from vaccines that were not protective.”
Attention at Bridge HIV will now turn to seven other potential HIV vaccines it currently has in the trial phase. Asked if finding an HIV vaccine that works is a lost cause, Buchbinder responded, “No, not at all.”
The results from both failed vaccine studies, as well as the successes from the Thai-based trial, are helping researchers better understand what is needed to construct an HIV vaccine that will work.
“We are trying to close in on understanding what we need an HIV vaccine to do in order for it to be preventive,” said Buchbinder.