September 28, 2009
After years of failure and frustration, a major breakthrough has been announced in the field of HIV/AIDS vaccine development: For the first time, a vaccine candidate has been found to be at least partly effective in protecting humans from HIV. The U.S. Army Surgeon General, the official sponsor of the trial, announced on Sept. 24 that a six-month regimen consisting of a "prime-boost" combination of two vaccines was found to be safe and lowered the risk of getting HIV by 31.2 percent compared to placebo.
But is this story truly as game-changing as most news headlines initially made it seem?
As the news made its way through mainstream news outlets, many HIV/AIDS activists were less than impressed. One of the first groups to voice caution was Gay Men's Health Crisis, one of the biggest HIV/AIDS organizations in the U.S. "While these results give us great hope, a fully effective HIV vaccine is still a ways off," warned Marjorie J. Hill, the group's CEO. "In the meantime, we know that using condoms and not sharing needles are two of the most effective HIV prevention technologies. With 7,500 people newly infected each day around the world, comprehensive sex education and access to proven prevention tools can prevent thousands of HIV infections right now."
Another organization, Treatment Action Group (TAG), one of the oldest and most respected HIV/AIDS treatment activist organizations in the U.S., offered even stronger reservations. "[B]ased on the limited amount of information that has been released, it appears that the statistical significance [of the results] hangs on very few cases of HIV infection," it said in a statement. "TAG urges caution in interpreting the findings until more detailed information is available."
Other organizations and members of the scientific community responded to the study results enthusiastically, although none suggested that the modestly optimistic results from this study mean that a fully effective HIV/AIDS vaccine is right around the corner.
The AIDS Vaccine Advocacy Coalition (AVAC), which was not associated with the study, was particularly effusive, issuing its own press release.
"Today marks an historic milestone in the search for an AIDS vaccine; we now have evidence that it is possible to reduce the risk [of] HIV infection with a vaccine," said AVAC executive director Mitchell Warren. "It will take time and resources to fully analyze, understand and validate the data, but there is little doubt that this finding will energize and redirect the AIDS vaccine field as all of us begin the hard work to translate this landmark result into true public health benefit."
The trial, known as the Thai Phase III HIV Vaccine Trial (or RV144), was the largest HIV/AIDS vaccine study ever conducted in humans. Although it was sponsored by the U.S. Army Surgeon General, it took place in Thailand and was conducted by the Thai Ministry of Public Health in collaboration with Thai and U.S. researchers.
The trial had been controversial. Many well-known researchers in the HIV/AIDS vaccine field had not expected a positive result, since the two vaccines used in RV144 had each been tested separately in smaller trials, and neither had been found to have any protective benefit against HIV.
In an editorial that was published in Science in January 2004, soon after RV144 began, 20 HIV/AIDS researchers expressed their displeasure: "The scientific rationale that has been offered for the new trial in Thailand is considered by the authors to be weak," they wrote.
Nonetheless, the study continued -- and it was a massive undertaking. The US$105 million study (75 percent of the funding came from the U.S. National Institute of Allergy and Infectious Diseases [NIAID], the rest from the U.S. Army) began in October of 2003 and did not end until June of 2009. Of the 60,000 people who were initially recruited for the trial (26,675 of whom were screened), 16,402 men and women between 18 and 30 years of age were selected for enrollment and split almost evenly into two groups: One group received a placebo, while the other received six doses over six months of the prime-boost vaccine.
The volunteers had varying levels of risk for HIV infection, with only a minority being members of groups that are traditionally considered to be at "high risk," such as men who have sex with men or intravenous drug users. The study was not designed to examine the prime-boost vaccine's efficacy in these high-risk groups, according to Merlin Robb, M.D., the HIV program director for the U.S. Military HIV Research Program, which sponsored the trial.
The 8,197 volunteers who were selected to get the prime-boost vaccine regimen received the following:
HIV testing took place every six months for three years. Participants also received HIV prevention counseling at each clinic visit. The researchers noted that they didn't see evidence that participants had increased their HIV risk behavior during the study.
In the final analysis of the trial, 74 of the 8,198 volunteers who received the placebo became infected with HIV, compared with 51 of the 8,197 volunteers who received the prime-boost vaccine regimen, meaning volunteers who received the vaccine were 31.2 percent less likely to become HIV positive after three years of follow-up.
The findings met (albeit barely) the scientific definition of "statistical significance," which means that the results of the study are most likely not due to chance. However, some scientists are muttering that the results are underwhelming for the astonishing amount of publicity that is being generated by this news.
Much analysis on the findings still needs to be done. For instance, it is not known which of the two vaccines in the regimen offered the greater level of protection, or how important it was that two vaccines were given instead of just one.
For those who were infected with HIV during the trial, the researchers did not see any sign that the prime-boost vaccine affected their viral load. The majority of the HIV-positive participants will be followed in another trial; all received HIV treatment and care as a part of the study.
It is worth noting that the vaccine was not designed to protect against every strain of HIV. The vaccine was created to test against two HIV subtypes: B, which is the most common strain in the U.S. and Europe, and E, which is the most common strain in Asia. However, about 85 to 90 percent of the population in this trial has HIV subtype E, and the majority of the HIV infections in the trial also occurred in people with this subtype. Therefore, it's still unknown whether this vaccine has the same effectiveness against subtype B as against subtype E, or whether it works the same in other areas of the world and against other strains of HIV.
However, the news that this vaccine had any benefit at all is extremely welcome. After so many HIV/AIDS vaccine trial failures, it has powerful implications for our long journey to create a viable vaccine.
At this point, there is no plan for the prime-boost vaccine to be widely manufactured or distributed. Although the regimen did appear to be effective, it may not be effective enough to make it worth using widely, according to Dr. Robb. "The vaccine may not be beneficial in a population that feels protected and changes their risk activity," he said, suggesting that the vaccine's 31.2 percent efficacy rate might be offset if people who receive the vaccine feel that it makes it OK for them to engage in unprotected sex or needle sharing.
However, the researchers are fast-tracking consultation with scientific and product development experts to figure out what their next steps should be in terms of research. "Knowledge gained through this study will be used to accelerate future study design and testing as researchers continue the search for a safe, globally-effective HIV vaccine," said Col. Jerome Kim, the HIV/AIDS vaccines product manager for the U.S. Army.
The study, its findings and its implications for the future will be discussed in much greater detail at the annual AIDS Vaccine Conference, which takes place next in Paris, France, at the end of October.
For the nitty-gritty on this trial, be sure to check out our collection of articles.
Stay tuned for an interview with HIV/AIDS vaccine advocates and more analysis on this trial.